KEGG ID
stringlengths 6
6
| Name
stringlengths 3
40
| Formula
stringlengths 2
40
⌀ | PubChem ID
int64 137
171M
| Molecular Weight
float64 2.02
8.95k
| LogP
float64 -61.1
26.8
⌀ | TPSA
float64 0
4.05k
| Complexity
int64 0
24.4k
| Hydrogen Bond Donors
int64 0
100
| Hydrogen Bond Acceptors
int64 0
204
| SMILES
stringlengths 1
1.09k
| Description
stringlengths 21
4.22k
| Toxicity
stringlengths 3
21.4k
⌀ | Drug Information
stringlengths 9
20.5k
⌀ | Pharmacodynamics
stringlengths 3
29.3k
⌀ | Solubility
float64 -142
7.55k
⌀ | pKa
float64 -7
8.44k
⌀ | SDF Structure
stringlengths 67
73
⌀ |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
D00001
|
Water
|
H2O
| 962
| 18.015
| -0.5
| 1
| 0
| 1
| 1
|
O
|
Water appears as a clear, nontoxic liquid composed of hydrogen and oxygen, essential for life and the most widely used solvent. Include water in a mixture to learn how it could react with other chemicals in the mixture.
|
sterile water
|
For diluting or dissolving drugs for intravenous, intramuscular or subcutaneous injection, according to instructions of the manufacturer of the drug to be administered. FDA Label
|
Tritium radioactivity in mouse fetus taken from the pregnant female mouse which had been given tritium containing drinking water was measured to estimate the absorbed radiation dose from the incorporated tritium. BC3F1 female mice mated with ICR male were given drinking water containing various concentrations of tritium for whole pregnant period, from the morning when the vaginal plug was observed to the day just before term. At various times of the pregnant period, blood and fetuses were taken from the female mice to measure the tritium concentration using a Packard model of sample oxidizer. The absorbed radiation dose of the fetus from the incorporated tritium was estimated on the basis of the tritium concentration measured. The tritium concentration of the embryos increased gradually from the first pregnant day to reach the plateau level at the 7 to 9th day. The estimated radiation dose increased almost linearly depending on the tritium concentration in the drinking water. /Tritium containing drinking water/
| null | null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/962.sdf
|
D00002
|
Nadide
|
C21H28N7O14P2
| 5,892
| 663.4
| -6
| 321
| 1,120
| 7
| 18
|
C1=CC(=C[N+](=C1)C2C(C(C(O2)COP(=O)([O-])OP(=O)(O)OCC3C(C(C(O3)N4C=NC5=C(N=CN=C54)N)O)O)O)O)C(=O)N
|
NAD zwitterion is a NAD. It has a role as a geroprotector. It is functionally related to a deamido-NAD zwitterion. It is a conjugate base of a NAD(+).
| null |
No drug information available
|
No pharmacodynamics information available
| 752.5
| null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5892.sdf
|
D00003
|
Oxygen
|
O2
| 977
| 31.999
| -1.1
| 34.1
| 0
| 0
| 2
|
O=O
|
Oxygen is a colorless, odorless and tasteless gas. It will support life. It is noncombustible, but will actively support the burning of combustible materials. Some materials that will not burn in air will burn in oxygen. Materials that burn in air will burn more vigorously in oxygen. As a non-liquid gas it is shipped at pressures of 2000 psig or above. Pure oxygen is nonflammable. Under prolonged exposure to fire or intense heat the containers may rupture violently and rocket. Oxygen is used in the production of synthesis gas from coal, for resuscitation and as an inhalant.
|
The substance can be absorbed into the body by inhalation.
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Oxygen therapy in clinical settings is used across diverse specialties, including various types of anoxia, hypoxia or dyspnea and any other disease states and conditions that reduce the efficiency of gas exchange and oxygen consumption such as respiratory illnesses, trauma, poisonings and drug overdoses. Oxygen therapy tries to achieve hyperoxia to reduce the extent of hypoxia-induced tissue damage and malfunction. For oxygen supplementation and as a carrier gas during inhalation anaesthesia. For oxygen supplementation during recovery.
|
Oxygen therapy improves effective cellular oxygenation, even at a low rate of tissue perfusion. Oxygen molecules adjust hypoxic ventilatory drive by acting on chemoreceptors on carotid bodies that sequentially relay sensory information to the higher processing centers in brainstem. It also attenuates hypoxia-induced mitochondrial depolarization that generates reactive oxygen species and/or apoptosis. Studies investigating on hyperbaric oxygen therapy has shown that oxygen supplementation can induce neural stem cell proliferation in neonatal rats thus promoting neurological regeneration after injuries. CD34+, CD45-dim leukocytes are also potential targets for hyperbaric oxygen therapy benefit as their mobilization was increased in vitro which could facilitate the acceleration of recovery at peripheral sites. QV03AN01 V - Various V03AN01 Man is designed to breathe 20.93% oxygen at atmospheric pressure or 14.7 psi absolute. Oxygen ... accounts for approximately 65% by weight of the human body ... Its greatest importance is the dependence of most life forms on O2 as a source of cellular energy ... On entry into the cells, the mitochondria use the diffused O2 in chemical reactions that ultimately supply the energy required for cellular functions. Most O2 combines with carbon and hydrogen atoms from glucose molecules to form cellular energy, known as adenosine triphosphate or ATP, along with carbon dioxide (CO2) and water. The remaining O2 is combined with various compounds to synthesize cellular structures or elimination products ... For each liter of O2 used, approximately 5 kcal (~20 J) of energy is liberated ... Hypoxia is a life-threatening condition in which oxygen delivery is inadequate to meet the metabolic demands of the tissues. Since oxygen delivery is the product of blood flow and oxygen content, hypoxia may result from alterations in tissue perfusion, decreased oxygen tension in the blood, or decreased oxygen carrying capacity. In addition, hypoxia may result from a problem in oxygen transport from the microvasculature to the cells or in utilization within the cell. Irrespective of cause, an inadequate supply of oxygen ultimately results in the cessation of aerobic metabolism and oxidative phosphorylation, depletion of high-energy cmpd, cellular dysfunction, and death. Tissue oxygen deficiency (hypoxia) ... may be defined as a decrease in O2 delivery to the cells resulting in an energy production that is below the cellular requirements ... Hypoxic effects are usually undetectable when PO2 is greater than 120 mm Hg. Interference with the adaptation of the eye to darkness, however, can occur at this pressure. For more Bionecessity (Complete) data for OXYGEN (10 total), please visit the HSDB record page. Exhalation During inhalation of normal air the arterial blood leaves lungs about 95% saturated with oxygen, and with a subject standing at rest, the venous blood returns to lungs about 60 to 70% saturated. During 1 min approx 360 cc of oxygen are used up. After forced deep inspiration normal lung vol is about 5 to 5.5 L, 1 L which is O2 ... Arterial blood carries O2 in 2 forms. Most is normally bound to hemoglobin ... A smaller amt is free in soln. The amount of O2 carried ... depends on partial pressure of oxygen. When fully saturated with O2, each g of hemoglobin binds 1.3 vol % of O2. At 37 °C, 0.003 vol % O2 is dissolved in blood/torr of partial pressure of O2. Fetal hemoglobin has more affinity for oxygen than maternal hemoglobin under similar conditions of pH & temp. If incompletely oxygen-saturated fetal & maternal blood are allowed to equilibrate across a membrane, partial pressure of O2 will be identical on both sides of membrane, but O2 content of fetal blood ... /will be/ higher ... Oxygen enters the body primarily through the lungs, but may also be taken up by mucous membranes of the GI tract, the middle ear, and the paranasal sinuses. It diffuses from the alveoli into the pulmonary capillaries, dissolves in the blood plasma, enters the red blood cells, and binds to hemoglobin. The red cells transport bound O2 to tissues throughout the body via the circulatory system. In tissues where the partial pressure of O2 is lower than that of the blood, the O2 diffuses out of the red cells, through the capillaries and plasma, and into the cells. As the O2 plasma concentration diminishes, it is replaced by that contained in the red cells. The red blood cells are then circulated back to the lungs in a continuous recycling process ... ... Most O2 combines with carbon and hydrogen atoms from glucose molecules to form cellular energy, known as adenosine triphosphate or ATP, along with carbon dioxide (CO2) and water. The remaining O2 is combined with various compounds to synthesize cellular structures or elimination products. The CO2 generated in the cells then diffuses back to the red blood cells and returns to the lungs, where it is exhaled. The metabolic water combines with ingested water and the excess is eliminated by excretion through the kidneys or by evaporation from the lungs and skin. In the course of O2 metabolism, several toxic substances are generated, including superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH-), lipid peroxides, and others. Without the availability of several enzymes that destroy these toxic intermediary compounds, cell death quickly occurs. The protective enzymes include superoxide dismutases (SODs), catalase (CAT), and glutathione peroxidase (GP). Glutathione reductase (GR) participates by re-forming glutathione, which is preferentially oxidized, thereby sparing sulfhydryl-bearing proteins and cell wall constituents. Other contributors to the control of oxidant toxicity include vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), vitamin A, and selenium, a cofactor for GP. Oxygen (O2) is reduced by both enzymatic and nonenzymatic processes to the superoxide radical (O2-). This radical species of oxygen is postulated to be formed in vivo in animals through activity of some iron-sulfur oxidation-reduction enzymes and certain flavoproteins ... The partial reduction of molecular oxygen in biological systems produces the cytotoxic intermediates superoxide, hydrogen peroxide, and hydroxyl radical. The superoxide radical is now recognized to play significant roles in a number of pathophysiologic states including oxygen toxicity, radiation damage, phagocyte-mediated inflammation, and postischemic injury. Oxygen toxicity is mediated through increased production of partially reduced oxygen products such as superoxide anion, perhydroperoxy and hydroxyl radicals, peroxynitrite and possibly singlet molecular oxygen. Approximately 122.24 seconds Oxygen therapy increases the arterial pressure of oxygen and is effective in improving gas exchange and oxygen delivery to tissues, provided that there are functional alveolar units. Oxygen plays a critical role as an electron acceptor during oxidative phosphorylation in the electron transport chain through activation of cytochrome c oxidase (terminal enzyme of the electron transport chain). This process achieves successful aerobic respiration in organisms to generate ATP molecules as an energy source in many tissues. Oxygen supplementation acts to restore normal cellular activity at the mitochondrial level and reduce metabolic acidosis. There is also evidence that oxygen may interact with O2-sensitive voltage-gated potassium channels in glomus cells and cause hyperpolarization of mitochondrial membrane. The exact mechanism whereby hypoxic pulmonary vasoconstriction is elicited is still unsettled. A possible role for toxic oxygen metabolites was evaluated, employing a set-up of blood-perfused isolated rat lungs. Hypoxic pulmonary vasoconstriction reflected as pulmonary arterial pressor responses, was evoked by alternately challenging the airways with a hypoxic- and a normoxic gas mixture, resulting in gradually increasing responses until a maximum was obtained. In a sequence of responses (mean +/- s.e. mean) increasing from 2.5 +/ - 0.2 kPa to 3.2 +/ - 0.1 kPa, administration to the perfusate of the inhibitor of xanthine oxidase, allopurinol reduced the subsequent response to 2.5 +/- 0.2 kPa (P < 0.001). By contrast, allopurinol did not affect vasoconstriction induced by serotonin or bradykinin. In control experiments responses continued to increase after administration of hypoxanthine (substrate of xanthine oxidase). Neither pretreatment with daily injections of the antioxidant vitamin E for 3 days in advance, nor addition to the perfusate of the scavenger enzymes superoxide dismutase and catalase, or dimethylsulfoxide had any impact on hypoxic pulmonary vasoconstriction; the subsequent responses rose at the same rate and in the same way as before. Thus, the present study has shown that allopurinol inhibition of xanthine oxidase depresses hypoxic pulmonary vasoconstriction. This could be due either to reduced production of toxic oxygen metabolites or to accumulation of purine metabolites. The absence of inhibitory effects of quenchers of toxic oxygen metabolites refutes a role for these metabolites in the elicitation of hypoxic pulmonary vasoconstriction. More likely, allopurinol inhibits hypoxic pulmonary vasoconstriction by interfering with the purine metabolism. Exposure to hyperoxia results in endothelial necrosis followed by type II cell proliferation. This suggests that type II cells are resistant to hyperoxia. Oxygen-induced lung injury may result from an overproduction of oxygen metabolites normally scavenged by antioxidants such as superoxide dismutase, glutathione peroxidase, catalase and reduced glutathione. Therefore, resistance of type II cells to hyperoxia may be linked to high antioxidant activities. To test this hypothesis /the authors/ compared in vitro the effects of a 24 hr exposure period to 95% O2 on cultured type II cells, lung fibroblasts and alveolar macrophages isolated from rats. We show that type II cells, when compared with other cell types, are highly sensitive to hyperoxia as shown by increased lactate dehydrogenase release, decreased deoxyribose nucleic acid and protein content of Petri dishes and decreased thymidine incorporation into DNA. Synthesis of dipalmitoylphosphatidylcholine was also significantly reduced. Antioxidant enzyme activities as well as glutathione content were not higher in type II cells than in other cell types. However, hyperoxia results in a decreased superoxide dismutase activity and glutathione content in type II cells which was not observed in fibroblasts. /It was concluded/ that adaptative changes in superoxide dismutase and glutathione metabolism could be important defense mechanisms in cells exposed to hyperoxia. Oxygen, essential for mammalian life, is paradoxically harmful. If O2 is given at high enough concentrations for long enough times, the body's protective mechanisms are overwhelmed, leading to cellular injury and, with continued exposure, even death. In the course of O2 metabolism, several toxic substances are generated, including superoxide anion (O2-), hydrogen peroxide (H2O2), hydroxyl radical (OH-), lipid peroxides, and others. Without the availability of several enzymes that destroy these toxic intermediary compounds, cell death quickly occurs. The protective enzymes include superoxide dismutases (SODs), catalase (CAT), and glutathione peroxidase (GP). Glutathione reductase (GR) participates by re-forming glutathione, which is preferentially oxidized, thereby sparing sulfhydryl-bearing proteins and cell wall constituents. Other contributors to the control of oxidant toxicity include vitamin C (ascorbic acid), vitamin E (alpha-tocopherol), vitamin A, and selenium, a cofactor for GP. Normally, a balance exists between the production of toxic oxidants and their destruction by antioxidant mechanisms. Some individuals may lack the ability to produce sufficient antioxidants and suffer a slow progressive tissue deterioration as a result. Protein accumulation in the BAL fluid results from damage to the pavement-like cells that line the alveolar sacs, known as type I cells, which cover 95% of the alveolar surface. Type I cells are generally incapable of dividing, but when damaged, can be replaced by the type II alveolar cells interspersed among them. Type II cells are less susceptible to toxic injury, can proliferate rapidly, and can be transformed into type I cells. Toxic injuries that affect only type I cells can be repaired by this proliferative process. To the extent that type II cells are also injured, the effects are more severe and may lead to permanent changes. Other types of cells in the lung are also affected, especially the capillary endothelial cells, leading to leakage of blood plasma into the interstitial tissue between the alveoli, and ultimately into the alveoli. Blood cells in the capillaries may also form a clot or may leak into alveolar spaces (hemorrhage). Other cells in the interstitium, such as fibroblasts, are damaged. An inflammatory response, with infiltration of white blood cells, proliferation of fibroblasts, and subsequent fibrosis may follow. For more Mechanism of Action (Complete) data for OXYGEN (11 total), please visit the HSDB record page.
| 39
| null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/977.sdf
|
D00004
|
Carbon
|
CO2
| 5,462,310
| 12.011
| 0.6
| 0
| 0
| 0
| 0
|
[C]
|
Carbon, activated is a black grains that have been treated to improve absorptive ability. May heat spontaneously if not properly cooled after manufacture.
|
Carbon nanotubes, multiwalled MWCNT-7
|
No drug information available
|
EXPTL INTRAVENOUS INJECTION OF PURE CARBON SUSPENSIONS IN RABBITS PRODUCES NO OCULAR INFLAMMATION, ALTHOUGH CARBON PARTICLES ARE DEPOSITED WITHIN THE BLOOD VESSELS.
| null | null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5462310.sdf
|
D00006
|
Pyridoxal
|
C8H10NO6P.
| 1,050
| 167.16
| 0
| 70.4
| 162
| 2
| 4
|
CC1=NC=C(C(=C1O)C=O)CO
|
Pyridoxal is a pyridinecarbaldehyde that is pyridine-4-carbaldehyde bearing methyl, hydroxy and hydroxymethyl substituents at positions 2, 3 and 5 respectively. The 4-carboxyaldehyde form of vitamin B6, it is converted into pyridoxal phosphate, a coenzyme for the synthesis of amino acids, neurotransmitters, sphingolipids and aminolevulinic acid. It has a role as a cofactor, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a vitamin B6, a pyridinecarbaldehyde, a member of methylpyridines, a monohydroxypyridine and a hydroxymethylpyridine. It is a conjugate base of a pyridoxal(1+).
| null |
Pyridoxal is one of the natural forms available of vitamin B6, therefore, it is used for nutritional supplementation and for treating dietary shortage or imbalances.
|
Pyridoxal principally in the form of the coenzyme pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA). A group of water-soluble vitamins, some of which are COENZYMES. (See all compounds classified as Vitamin B Complex.) Pyridoxal is the precursor to pyridoxal phosphate. Pyridoxal 5'-phosphate is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).
| 500
| null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/1050.sdf
|
D00008
|
Hydrogen
|
H2O2
| 783
| 2.016
| 0
| 0
| 0
| 0
| 0
|
[HH]
|
Hydrogen is a colorless, odorless gas. It is easily ignited. Once ignited it burns with a pale blue, almost invisible flame. The vapors are lighter than air. It is flammable over a wide range of vapor/air concentrations. Hydrogen is not toxic but is a simple asphyxiate by the displacement of oxygen in the air. Under prolonged exposure to fire or intense heat the containers may rupture violently and rocket. Hydrogen is used to make other chemicals and in oxyhydrogen welding and cutting.
|
IDENTIFICATION AND USE: Hydrogen is a colorless gas. Its many uses include the following: production of ammonia, ethanol, and aniline; hydrocracking, hydroforming, and hydrofining of petroleum; hydrogenation of vegetable oils; hydrogenolysis of coal; reducing agent for organic synthesis and metallic ores; reducing atmosphere to prevent oxidation; as oxyhydrogen flame for high temperatures; atomic-hydrogen welding; instrument-carrying balloons; making hydrogen chloride and hydrogen bromide; production of high-purity metals; fuel for nuclear rocket engines for hypersonic transport; missile fuel; cryogenic research. In addition, hydrogen is a versatile energy carrier that can be used to power nearly every end-use energy need (Fuel cells). Molecular hydrogen (H2) emerged as a novel therapeutic agent, with antioxidant, anti-inflammatory and anti-apoptotic effects demonstrated in plethora of animal disease models and human studies. HUMAN STUDIES: Hydrogen is a simple asphyxiant. Contact with liquid hydrogen will cause frostbite or severe burns of the skin. Hydrogen-rich water has been tested for treating oxidative stress-induced disorders because of its reactive oxygen species scavenging abilities. Hydrogen therapy may be an effective and specific innovative treatment for exercise-induced oxidative stress and sports injury, with potential for the improvement of exercise performance. ANIMAL STUDIES: A large bubble of the gas injected into anterior chamber of rabbit eyes was absorbed within three days and caused no injury. H2 was believed to be inert and nonfunctional in mammalian cells. More recently it was demonstrated that H2 reacts with highly reactive oxidants such as hydroxyl radical and peroxynitrite inside cells. Beneficial effects of molecular hydrogen in animal models were observed especially in oxidative stress-mediated diseases, such as diabetes mellitus, brain stem infarction, rheumatoid arthritis, or neurodegenerative diseases. H2 affects cell signal transduction.
|
No drug information available
|
Molecular hydrogen (H2) is an agent with potential applications in oxidative stress-related and/or inflammatory disorders. H2 is usually administered by inhaling H2-containing air (HCA) or by oral intake of H2-rich water (HRW). Despite mounting evidence, the molecular mechanism underlying the therapeutic effects and the optimal method of H2 administration remain unclear. Here, we investigated whether H2 affects signaling pathways and gene expression in a dosage- or dose regimen-dependent manner. We first examined the H2 concentrations in blood and organs after its administration and found that oral intake of HRW rapidly but transiently increased H2 concentrations in the liver and atrial blood, while H2 concentrations in arterial blood and the kidney were one-tenth of those in the liver and atrial blood. In contrast, inhalation of HCA increased H2 equally in both atrial and arterial blood ... Hydrogen exerts beneficial effects in disease animal models of ischemia-reperfusion injury as well as inflammatory and neurological disease. Additionally, molecular hydrogen is useful for various novel medical and therapeutic applications in the clinical setting. In the present study, the hydrogen concentration in rat blood and tissue was estimated. Wistar rats were orally administered hydrogen super-rich water (HSRW), intraperitoneal and intravenous administration of hydrogen super-rich saline (HSRS), and inhalation of hydrogen gas. A new method for determining the hydrogen concentration was then applied using ... sensor gas chromatography, after which the specimen was prepared via tissue homogenization in airtight tubes. This method allowed for the sensitive and stable determination of the hydrogen concentration. The hydrogen concentration reached a peak at 5 minutes after oral and intraperitoneal administration, compared to 1 minute after intravenous administration. Following inhalation of hydrogen gas, the hydrogen concentration was found to be significantly increased at 30 minutes and maintained the same level thereafter. These results demonstrate that accurately determining the hydrogen concentration in rat blood and organ tissue is very useful and important for the application of various novel medical and therapeutic therapies using molecular hydrogen. /Hydrogen super-rich water or saline/ The ability of mammalian tissues to oxidize hydrogen under conditions similar to those encountered by deep divers breathing mixtures containing hydrogen was investigated. The kidneys, livers, spleen, heart, lungs, and quadriceps muscle were removed from guinea-pigs and rats. After mincing or homogenization, the tissues, along with myocytes prepared from rat hearts and porcine cerebral cortex capillary endothelial cells were placed in petri dishes and exposed to tritium tagged hydrogen at a pressure of 1 or 5 megapascals (MPa) for 1 hour in a specially designed exposure system. Helium at a pressure of 1 MPa was used as a carrier. Petri dishes filled with distilled water or saline served as negative controls. After decompression, the extent of hydrogen oxidized by the mammalian tissues and cells was determined by measuring the amounts of incorporated tritium by liquid scintillation counting. The tissues and cells incorporated tritium only at the rate of 10 to 50 nanomoles per gram per minute (nmol/g/min), rates that were similar to those of the negative controls. The authors conclude that mammalian tissues do not oxidize hydrogen under hyperbaric conditions. The small amounts of tritium label incorporation observed in the tissues is probably due to radioisotope phenomena, which sets the detection limit for determining hydrogen oxidation at 100 nmol/g/min. Substantial evidence indicates that molecular hydrogen (H2) has beneficial vascular effects because of its antioxidant and/or anti-inflammatory effects. Thus, hydrogen-rich water may prove to be an effective anti-aging drink. This study examined the effects of H2 on endothelial senescence and clarified the mechanisms involved. Hydrogen-rich medium was produced by a high-purity hydrogen gas generator. Human umbilical vein endothelial cells (HUVECs) were incubated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) for various time periods in normal or hydrogen-rich medium. The baseline H2concentration in hydrogen-rich medium was 0.55 +/- 0.07 mmol/L. This concentration gradually decreased, and H2 was almost undetectable in medium after 12 hr. At 24 hr after TCDD exposure, HUVECs treated with TCDD exhibited increased 8OHdG and acetyl-p53 expression, decreased nicotinamide adenine dinucleotide (NAD(+))/NADH ratio, impaired Sirt1 activity, and enhanced senescence-associated beta-galactosidase. However, HUVECs incubated in hydrogen-rich medium did not exhibit these TCDD-induced changes accompanying Nrf2 activation, which was observed even after H2 was undetectable in the medium. Chrysin, an inhibitor of Nrf2, abolished the protective effects of H2 on HUVECs. H2 has long-lasting antioxidant and anti-aging effects on vascular endothelial cells through the Nrf2 pathway, even after transient exposure to H2. Hydrogen-rich water may thus be a functional drink that increases longevity. /Hydrogen-rich water/ Amyloid beta (Abeta) peptides are identified /as a/ cause of neurodegenerative diseases such as Alzheimer's disease (AD). Previous evidence suggests Abeta-induced neurotoxicity is linked to the stimulation of reactive oxygen species (ROS) production. The accumulation of Abeta-induced ROS leads to increased mitochondrial dysfunction and triggers apoptotic cell death. This suggests antioxidant therapies may be beneficial for preventing ROS-related diseases such as AD. Recently, hydrogen-rich water (HRW) has been proven effective in treating oxidative stress-induced disorders because of its ROS-scavenging abilities. However, the precise molecular mechanisms whereby HRW prevents neuronal death are still unclear. In the present study, we evaluated the putative pathways by which HRW protects against Abeta-induced cytotoxicity /in SK-N-MC cells/. Our results indicated that HRW directly counteracts oxidative damage by neutralizing excessive ROS, leading to the alleviation of Abeta-induced cell death. In addition, HRW also stimulated AMP-activated protein kinase (AMPK) in a sirtuin 1 (Sirt1)-dependent pathway, which upregulates forkhead box protein O3a (FoxO3a) downstream antioxidant response and diminishes Abeta-induced mitochondrial potential loss and oxidative stress. Taken together, our findings suggest that HRW may have potential therapeutic value to inhibit Abeta-induced neurotoxicity. /Hydrogen-rich water/ The NLRP3 inflammasome, an intracellular multi-protein complex controlling the maturation of cytokine interleukin-1beta, plays an important role in lipopolysaccharide (LPS)-induced inflammatory cascades. Recently, the production of mitochondrial reactive oxygen species (mtROS) in macrophages stimulated with LPS has been suggested to act as a trigger during the process of NLRP3 inflammasome activation that can be blocked by some mitochondria-targeted antioxidants. Known as a ROS scavenger, molecular hydrogen (H2) has been shown to possess therapeutic benefit on LPS-induced inflammatory damage in many animal experiments. Due to the unique molecular structure, H2 can easily target the mitochondria, suggesting that H2 is a potential antagonist of mtROS-dependent NLRP3 inflammasome activation. Here we have showed that, in mouse macrophages, H2 exhibited substantial inhibitory activity against LPS-initiated NLRP3 inflammasome activation by scavenging mtROS. Moreover, the elimination of mtROS by H2 resultantly inhibited mtROS-mediated NLRP3 deubiquitination, a non-transcriptional priming signal of NLRP3 in response to the stimulation of LPS. Additionally, the removal of mtROS by H2 reduced the generation of oxidized mitochondrial DNA and consequently decreased its binding to NLRP3, thereby inhibiting the NLRP3 inflammasome activation. Our findings have, for the first time, revealed the novel mechanism underlying the inhibitory effect of molecular hydrogen on LPS-caused NLRP3 inflammasome activation, highlighting the promising application of this new antioxidant in the treatment of LPS-associated inflammatory pathological damage. ... H2 decreased the tyrosine nitration level and suppressed oxidative stress damage in retinal cells. S-nitroso-N-acetylpenicillamine treatment decreased the cell numbers in the ganglion cell layer and inner nuclear layer, but the presence of H2 inhibited this reduction. These findings suggest that H2 has a neuroprotective effect against retinal cell oxidative damage, presumably by scavenging peroxynitrite. H2 reduces cellular peroxynitrite, a highly toxic reactive nitrogen species. Thus, H2 may be an effective and novel clinical tool for treating glaucoma and other oxidative stress-related diseases. Endothelial injury is a primary cause of sepsis and sepsis-induced organ damage. Heme oxygenase-1 (HO-1) plays an essential role in endothelial cellular defenses against inflammation by activating nuclear factor E2-related factor-2 (Nrf2). We found that molecular hydrogen (H2) exerts an anti-inflammatory effect. Here, we hypothesized that H2 attenuates endothelial injury and inflammation via an Nrf2-mediated HO-1 pathway during sepsis. First, we detected the effects of H2 on cell viability and cell apoptosis in human umbilical vein endothelial cells (HUVECs) stimulated by LPS. Then, we measured cell adhesion molecules and inflammatory factors in HUVECs stimulated by LPS and in a cecal ligation and puncture (CLP)-induced sepsis mouse model. Next, the role of Nrf2/HO-1 was investigated in activated HUVECs, as well as in wild-type and Nrf(-/-) mice with sepsis. We found that both 0.3 mmol/L and 0.6 mmol/L (i.e., saturated) H2-rich media improved cell viability and cell apoptosis in LPS-activated HUVECs and that 0.6 mmol/L (i.e., saturated) H2-rich medium exerted an optimal effect. H2 could suppress the release of cell adhesion molecules, such as vascular cell adhesion molecule-1 (VCAM-1) and intercellular cell adhesion molecule-1 (ICAM-1), and pro-inflammatory cytokines, such as tumor necrosis factor (TNF)-a, interleukin (IL)-1beta and high-mobility group box 1 protein (HMGB1). Furthermore, H2 could elevate anti-inflammatory cytokine IL-10 levels in LPS-stimulated HUVECs and in lung tissue from CLP mice. H2 enhanced HO-1 expression and activity in vitro and in vivo. HO-1 inhibition reversed the regulatory effects of H2 on cell adhesion molecules and inflammatory factors. H2 regulated endothelial injury and the inflammatory response via Nrf2-mediated HO-1 levels. These results suggest that H2 could suppress excessive inflammatory responses and endothelial injury via an Nrf2/HO-1 pathway. /Hydrogen-rich media/
| 1.62
| null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/783.sdf
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D00009
|
Glucose
|
C6H12O6
| 5,793
| 180.16
| -2.6
| 110
| 151
| 5
| 6
|
C(C1C(C(C(C(O1)O)O)O)O)O
|
D-glucopyranose is a glucopyranose having D-configuration. It has a role as a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a D-glucose and a glucopyranose.
|
Very high serum levels of glucose are found in untreated diabetic (type I or type II) patients. Glucose in chronic excess causes toxic effects on the structure and function of many cells and organs, including the pancreas and pancreatic islet cells. Multiple biochemical pathways and mechanisms of action for glucose toxicity have been suggested. These include glyceraldehyde auto-oxidation, protein kinase C activation, methylglyoxal formation and glycation, hexosamine metabolism, sorbitol formation, and oxidative phosphorylation. All these pathways have in common the formation of reactive oxygen species that, in excess and over time, cause chronic oxidative stress, which in turn causes defective insulin gene expression and insulin secretion as well as increased apoptosis. Exposure of endothelial cells to high glucose causes GAPDH inhibition through reactive oxygen species-activated poly(ADP-ribosyl)ation of GAPDH by poly(ADP-ribose) polymerase. Three products from glucose metabolism (glyoxal, methylglyoxal, and 3-deoxyglucosone) form advanced glycation end products (AGEs) by reacting with amino groups on intracellular and extracellular proteins. AGEs play important roles in the pathogenesis of secondary complications of diabetes, especially with regard to microvascular disease in the retina, nerves, and kidney and likely islets. Glycated hemoglobin is a particularly important AGE. A 1% increase in absolute concentrations of glycated hemoglobin is associated with about 10-20% increase in cardiovascular disease risk.
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Glucose pharmaceutical formulations (oral tablets, injections) are indicated for caloric supply and carbohydrate supplementation in case of nutrient deprivation. It is also used for metabolic disorders such as hypoglycemia. FDA Label
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Blood glucose is an obligatory energy source for humans involved in various cellular activities, and it also acts as a signaling molecule for diverse glucose-sensing molecules and proteins. Glucose undergoes oxidation into carbon dioxide, water, and yields energy molecules in the process of glycolysis and subsequent citric cycle and oxidative phosphorylation. Glucose is readily converted into fat in the body which can be used as a source of energy as required. Under a similar conversion into storage of energy, glucose is stored in the liver and muscles as glycogen. Glucose stores are mobilized in a regulated manner, depending on the tissues' metabolic demands. Oral glucose tablets or injections serve to increase the supply of glucose and oral glucose administration is more effective in stimulating insulin secretion because it stimulates the incretin hormones from the gut, which promotes insulin secretion. Substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products. (From Random House Unabridged Dictionary, 2d ed) (See all compounds classified as Sweetening Agents.) V - Various B - Blood and blood forming organs V - Various B05CX01 Polysaccharides can be broken down into smaller units by pancreatic and intestinal glycosidases or intestinal flora. Sodium-dependent glucose transporter SGLT1 and GLUT2 (SLC2A2) play predominant roles in intestinal transport of glucose into the circulation. SGLT1 is located in the apical membrane of the intestinal wall while GLUT2 is located in the basolateral membrane, but it was proposed that GLUT2 can be recruited into the apical membrane after a high luminal glucose bolus allowing bulk absorption of glucose by facilitated diffusion. Oral preparation of glucose reaches the peak concentration within 40 minutes and the intravenous infusions display 100% bioavailability. Glucose can be renally excreted. The mean volume of distribution after intravenous infusion is 10.6L. The mean metabolic clearance rate of glucose (MCR) for the 10 subjects studied at the higher insulin level was 2.27 ± 0.37 ml/kg/min at euglycemia and fell to 1.51±0.21 ml/kg/ at hyperglycemia. The mean MCR for the six subjects studied at the lower insulin level was 1.91 ± 0.31 ml/kg/min at euglycemia. Glucose can undergo aerobic oxidation in conjunction with the synthesis of energy molecules. Glycolysis is the initial stage of glucose metabolism where one glucose molecule is degraded into two molecules of pyruvate via substrate-level phosphorylation. These products are transported to the mitochondria where they are further oxidized into oxygen and carbon dioxide. The approximate half-life is 14.3 minutes following intravenous infusion. Gut glucose half-life was markedly higher in females (79 ± 2 min) than in males (65 ± 3 min, P < 0.0001) and negatively related to body height (r = -0.481; P < 0.0001). Glucose supplies most of the energy to all tissues by generating energy molecules ATP and NADH during a series of metabolism reactions called glycolysis. Glycolysis can be divided into two main phases where the preparatory phase is initiated by the phosphorylation of glucose by hexokinase to form glucose 6-phosphate. The addition of the high-energy phosphate group activates glucose for the subsequent breakdown in later steps of glycolysis and is the rate-limiting step. Products end up as substrates for following reactions, to ultimately convert C6 glucose molecule into two C3 sugar molecules. These products enter the energy-releasing phase where the total of 4ATP and 2NADH molecules are generated per one glucose molecule. The total aerobic metabolism of glucose can produce up to 36 ATP molecules. These energy-producing reactions of glucose are limited to D-glucose as L-glucose cannot be phosphorylated by hexokinase. Glucose can act as precursors to generate other biomolecules such as vitamin C. It plays a role as a signaling molecule to control glucose and energy homeostasis. Glucose can regulate gene transcription, enzyme activity, hormone secretion, and the activity of glucoregulatory neurons. The types, number, and kinetics of glucose transporters expressed depends on the tissues and fine-tunes glucose uptake, metabolism, and signal generation to preserve cellular and whole body metabolic integrity.
| null | null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5793.sdf
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D00010
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Acetic
|
C2H4O2
| 176
| 60.05
| -0.2
| 37.3
| 31
| 1
| 2
|
CC(=O)O
|
Acetic acid, glacial appears as a clear colorless liquid with a strong odor of vinegar. Flash point 104 °F. Density 8.8 lb / gal. Corrosive to metals and tissue. Used to make other chemicals, as a food additive, and in petroleum production.
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IDENTIFICATION AND USE: Acetic acid is a colorless liquid or solid, having a pungent characteristic odor, and when diluted in water an acidic taste. Glacial acetic acid is a 99% active chemical. It is used as an acidifier, flavoring agent, for the prevention of rope in baking, and as a solvent. Acetic acid is used as a laboratory reagent in chemical and biochemical analysis, in field testing of lead fumes, vinyl chloride determination, uric acid in urine, aniline vapors, and separation of gases. In addition, acetic acid is used in pesticide formulations as a herbicide to controls weeds on fruits, vegetables, ornamentals and turf. It is also a component of the hydraulic fracturing fluids preventing precipitation of metal oxides (iron control). Registered for use in the U.S., but approved pesticide uses may change periodically, so federal, state and local authorities must be consulted for currently approved uses. Three to 5% acetic acid is commonly used in the field of gynecology for colposcopic examinations of the cervix. It gives an 'acetowhite' effect that may assist clinicians in identifying neoplastic areas. HUMAN EXPOSURE AND TOXICITY: Acetic acid is absorbed from the gastrointestinal tract and through the lungs and almost completely oxidized by tissues. The metabolic pathways are reasonably well known and involve the formation of ketone bodies. As little as 1.0 mL of glacial acetic acid has resulted in perforation of the esophagus. During acetic acid dialysis, patients showed a frequent onset of sudden hypotension and arrhythmia with concomitant symptoms of the so-called disequilibrium syndrome. Extreme eye and nasal irritation has occurred at concentrations in excess of 25 ppm and conjunctivitis from concentrations below 10 ppm has been reported. Glacial acetic acid has caused permanent corneal opacification. Ingestion of 200 mL of an 80% solution of acetic acid caused repeated shock due to myocardial infarction and massive intestinal bleeding led to an organic brain psychosyndrome. The patient survived the intoxication by use of hemodialysis and intensive care therapy. An excess of prostate cancer was observed among former chemical plant workers, some of whom had been exposed to both acetic acid and acetic anhydride. ANIMAL STUDIES: Toxic effects of acetic acid are due to irritant properties as well as its effect on the central nervous system and kidneys. Large oral doses cause CNS depression and death in rats and mice. Inhalation of 16,000 ppm killed 1 of 6 exposed rats. Groups of 3-6 rats were given acetic acid in drinking water for periods from 9-15 weeks. Fluid uptake was the same in all treatment groups, at the high dose group there was a progressive reduction in body weight gain, loss of appetite and fall in food consumption. Four groups of two young pigs were fed daily diets for successive 30 day periods for a total of 150 days. There were differences in growth rate, weight gain, early morning urinary ammonia and terminal blood pH between controls and test groups. Acetic acid had no effects on implantation or on maternal or fetal survival in rats, mice or rabbits dosed via gavage during gestation days 6-19 at doses up to 1600 mg/kg/day. The number of abnormalities seen in either soft or skeletal tissues of the test groups did not differ from the number occurring in the controls. Acetic acid has shown no evidence of mutagenic activity with or without metabolic activation using several strains of Salmonella typhimurium. Acetic acid did not show clastogenicity on cultured Chinese hamster ovary K1 cells at neutral pH, but it was clastogenic at pH 5.2 to 6.0 with or without metabolic activation. ECOTOXICITY STUDIES: Acetic acid was harmful to aquatic life. High concentrations produced pH levels toxic to oxidizing bacteria, inhibiting oxygen demand. It was lethal to Mosquito fish: at 320 ppm and higher all fish were dead at 24 hours.
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Used to treat infections in the ear canal.
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Substances used for the detection, identification, analysis, etc. of chemical, biological, or pathologic processes or conditions. Indicators are substances that change in physical appearance, e.g., color, at or approaching the endpoint of a chemical titration, e.g., on the passage between acidity and alkalinity. Reagents are substances used for the detection or determination of another substance by chemical or microscopical means, especially analysis. Types of reagents are precipitants, solvents, oxidizers, reducers, fluxes, and colorimetric reagents. (From Grant and Hackh's Chemical Dictionary, 5th ed, p301, p499) (See all compounds classified as Indicators and Reagents.) Substances that inhibit the growth or reproduction of BACTERIA. (See all compounds classified as Anti-Bacterial Agents.) G - Genito urinary system and sex hormones S - Sensory organs S02AA10 Acetic acid is absorbed from the GI tract and through the lung. Acetic acid ... is readily metabolized by most tissues and may give rise to the production of ketone bodies as intermediates. In vitro, acetate is incorporated into phospholipids, neutral lipids, steroids, sterols, and saturated and unsaturated fatty acids in a variety of human and animal tissue preparations. ...Metabolism of 14(C) acetate in mice results in radioactivity associated with the protein fractions of plasma and most major tissues. In the body, acetic acid is partially converted into formic acid. When dogs were administered large doses (1-2 g/kg ip or sc) of sodium acetate, only small amounts appeared in the urine, which is evidence of the rapid utilization of acetic acid. Acetic Acid is a known human metabolite of acetaldehyde. Lead is absorbed following inhalation, oral, and dermal exposure. It is then distributed mainly to the bones and red blood cells. In the blood lead may be found bound to serum albumin or the metal-binding protein metallothionein. Organic lead is metabolized by cytochrome P-450 enzymes, whereas inorganic lead forms complexes with delta-aminolevulinic acid dehydratase. Lead is excreted mainly in the urine and faeces. (L136) Acetic acid is is absorbed from the gastrointestinal tract and through the lungs. It is completely oxidized by the tissues, with metabolism involving the formation of ketone bodies. The products of acetic acid are used in the formation of glycogen, as intermediates of carbohydrates and fatty acid synthesis, and in cholesterol synthesis. In addition, acetic acid participates in the acetylation of amines and formation of proteins of plasma, liver, kidney, gut mucosa, muscle, and brain. (L1886) Although acetic acid has been shown to induce apoptosis in yeast, the exact apoptotic mechanisms remain unknown. Here, /the study examined/ the effects of acetic acid treatment on yeast cells by 2-DE, revealing alterations in the levels of proteins directly or indirectly linked with the target of rapamycin (TOR) pathway: amino-acid biosynthesis, transcription/translation machinery, carbohydrate metabolism, nucleotide biosynthesis, stress response, protein turnover and cell cycle. The increased levels of proteins involved in amino-acid biosynthesis presented a counteracting response to a severe intracellular amino-acid starvation induced by acetic acid. Deletion of GCN4 and GCN2 encoding key players of general amino-acid control (GAAC) system caused a higher resistance to acetic acid indicating an involvement of Gcn4p/Gcn2p in the apoptotic signaling. Involvement of the TOR pathway in acetic acid-induced apoptosis was also reflected by the higher survival rates associated to a terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-negative phenotype and lower reactive oxygen species levels of Deltator1 cells. In addition, deletion mutants for several downstream mediators of the TOR pathway revealed that apoptotic signaling involves the phosphatases Pph21p and Pph22p but not Sit4p. Altogether, /these/ results indicate that GAAC and TOR pathways (Tor1p) are involved in the signaling of acetic acid-induced apoptosis. Acetic acid was found to have actions on urinary bladder smooth muscle in /the/ routine ion channel screening assays. Numerous studies have examined the mechanisms of bladder irritation by acetic acid; however, the direct effect of acetic acid on ion channels in detrusor smooth muscle cells has not been evaluated. /The study/ used whole-cell patch-clamp techniques to examine the effect of acetic acid on large-conductance Ca2+-activated K+ channels (BKCa) from guinea pig detrusor smooth muscle cells and CHO cells expressing recombinant human BKCaalphabeta1 (CHO BKCaalphabeta1) and human BKCaalpha (CHO BKCaalpha). Acetic acid activated BKCa currents in a concentration-dependent (0.01% to 0.05% v/v) manner in all the cell systems studied. Acetic acid (0.05%) increased BKCa current at +30 mV by 2764 +/- 918% (n=8) in guinea pig detrusor smooth muscle cells. Acetic acid (0.03%) shifted the V1/2 of conductance-voltage curve by 64 +/- 14 (n=5), 128 +/- 14 (n=5), and 126 +/- 12 mV (n=4) in CHO BKCaalpha, CHO BKCaalphabeta1 and detrusor smooth muscle cells, respectively. This effect of acetic acid was found to be independent of pH and was also not produced by its salt form, sodium acetate. Automated patch-clamp experiments also showed similar activation of CHO BKCaalphabeta1 by acetic acid. In conclusion, acetic acid directly activates BKCa channels in detrusor smooth muscle cells. This novel study necessitates caution while interpreting the results from acetic acid bladder irritation model. /It was/ previously shown that acetic acid activates a mitochondria-dependent death process in Saccharomyces cerevisiae and that the ADP/ATP carrier (AAC) is required for mitochondrial outer membrane permeabilization and cytochrome c release. Mitochondrial fragmentation and degradation have also been shown in response to this death stimulus. Herein, /the study/ show that autophagy is not active in cells undergoing acetic acid-induced apoptosis and is therefore not responsible for mitochondrial degradation. Furthermore, /the study/ found that the vacuolar protease Pep4p and the AAC proteins have a role in mitochondrial degradation using yeast genetic approaches. Depletion and overexpression of Pep4p, an orthologue of human cathepsin D, delays and enhances mitochondrial degradation respectively. Moreover, Pep4p is released from the vacuole into the cytosol in response to acetic acid treatment. AAC-deleted cells also show a decrease in mitochondrial degradation in response to acetic acid and are not defective in Pep4p release. Therefore, AAC proteins seem to affect mitochondrial degradation at a step subsequent to Pep4p release, possibly triggering degradation through their involvement in mitochondrial permeabilization. The finding that both mitochondrial AAC proteins and the vacuolar Pep4p interfere with mitochondrial degradation suggests a complex regulation and interplay between mitochondria and the vacuole in yeast programmed cell death.
| 100
| 4.756
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/176.sdf
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D00011
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Glycine
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C2H5NO2
| 750
| 75.07
| -3.2
| 63.3
| 42
| 2
| 3
|
C(C(=O)O)N
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Glycine appears as white crystals. (NTP, 1992)
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In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia. <br/>Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS.
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Supplemental glycine may have antispastic activity. Very early findings suggest it may also have antipsychotic activity as well as antioxidant and anti-inflammatory activities.
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Helps trigger the release of oxygen to the energy requiring cell-making process; Important in the manufacturing of hormones responsible for a strong immune system. Substances used for their pharmacological actions on glycinergic systems. Glycinergic agents include agonists, antagonists, degradation or uptake inhibitors, depleters, precursors, and modulators of receptor function. (See all compounds classified as Glycine Agents.) B - Blood and blood forming organs Absorbed from the small intestine via an active transport mechanism. Hepatic Hepatic In the CNS, there exist strychnine-sensitive glycine binding sites as well as strychnine-insensitive glycine binding sites. The strychnine-insensitive glycine-binding site is located on the NMDA receptor complex. The strychnine-sensitive glycine receptor complex is comprised of a chloride channel and is a member of the ligand-gated ion channel superfamily. The putative antispastic activity of supplemental glycine could be mediated by glycine's binding to strychnine-sensitive binding sites in the spinal cord. This would result in increased chloride conductance and consequent enhancement of inhibitory neurotransmission. The ability of glycine to potentiate NMDA receptor-mediated neurotransmission raised the possibility of its use in the management of neuroleptic-resistant negative symptoms in schizophrenia. Animal studies indicate that supplemental glycine protects against endotoxin-induced lethality, hypoxia-reperfusion injury after liver transplantation, and D-galactosamine-mediated liver injury. Neutrophils are thought to participate in these pathologic processes via invasion of tissue and releasing such reactive oxygen species as superoxide. In vitro studies have shown that neutrophils contain a glycine-gated chloride channel that can attenuate increases in intracellular calcium and diminsh neutrophil oxidant production. This research is ealy-stage, but suggests that supplementary glycine may turn out to be useful in processes where neutrophil infiltration contributes to toxicity, such as ARDS. HYPERPOLARIZATION OF MOTONEURONS PRODUCED BY IONTOPHORETIC APPLICATION OF GLYCINE IS RELATIVELY TRANSIENT BUT APPROACHES THE EQUILIBRIUM POTENTIAL FOR THE INDIRECTLY ACTIVATED INHIBITORY POSTSYNAPTIC POTENTIAL...TESTS WITH GABA... INDICATE SIMILAR ELECTROPHYSIOLOGICAL EFFECTS & SIMILAR INCR IN CL- CONDUCTANCE. MAJOR EVIDENCE THAT FAVORS GLYCINE AS MEDIATOR OF INTRASPINAL POSTSYNAPTIC INHIBITION IS THE SELECTIVE ANTAGONISM OF ITS EFFECTS BY STRYCHNINE. ... GLYCINE ALSO APPEARS TO BE MOST LIKELY TRANSMITTER FOR INHIBITORY INTERNEURONS IN RETICULAR FORMATION BUT NOT IN CUNEATE NUCLEUS.
| 100
| 9.8
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/750.sdf
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D00012
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Alanine
|
C3H7NO2
| 5,950
| 89.09
| -3
| 63.3
| 61
| 2
| 3
|
CC(C(=O)O)N
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L-alanine is the L-enantiomer of alanine. It has a role as an EC 4.3.1.15 (diaminopropionate ammonia-lyase) inhibitor and a fundamental metabolite. It is a pyruvate family amino acid, a proteinogenic amino acid, a L-alpha-amino acid and an alanine. It is a conjugate base of a L-alaninium. It is a conjugate acid of a L-alaninate. It is an enantiomer of a D-alanine. It is a tautomer of a L-alanine zwitterion.
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L-Alanine is a non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. BCAAs are used as a source of energy for muscle cells. During prolonged exercise, BCAAs are released from skeletal muscles and their carbon backbones are used as fuel, while their nitrogen portion is used to form another amino acid, Alanine. Alanine is then converted to Glucose by the liver. This form of energy production is called the Alanine-Glucose cycle, and it plays a major role in maintaining the body's blood sugar balance.
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Used for protein synthesis.
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Is an important source of energy for muscle tissue, the brain and central nervous system; strengthens the immune system by producing antibodies; helps in the metabolism of sugars and organic acids. OF5P57N2ZX ALANINE Established Pharmacologic Class [EPC] - Amino Acid Chemical Structure [CS] - Amino Acids Alanine is an Amino Acid. L-Alanine is a non-essential amino acid that occurs in high levels in its free state in plasma. It is produced from pyruvate by transamination. It is involved in sugar and acid metabolism, increases immunity, and provides energy for muscle tissue, brain, and the central nervous system. BCAAs are used as a source of energy for muscle cells. During prolonged exercise, BCAAs are released from skeletal muscles and their carbon backbones are used as fuel, while their nitrogen portion is used to form another amino acid, Alanine. Alanine is then converted to Glucose by the liver. This form of energy production is called the Alanine-Glucose cycle, and it plays a major role in maintaining the body's blood sugar balance.
| null | 2.34
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5950.sdf
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D00014
|
Glutathione
|
C10H17N3O6S
| 124,886
| 307.33
| -4.5
| 160
| 389
| 6
| 8
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C(CC(=O)NC(CS)C(=O)NCC(=O)O)C(C(=O)O)N
|
Glutathione is a tripeptide compound consisting of glutamic acid attached via its side chain to the N-terminus of cysteinylglycine. It has a role as a skin lightening agent, a human metabolite, an Escherichia coli metabolite, a mouse metabolite, a geroprotector, an antioxidant and a cofactor. It is a tripeptide, a thiol and a L-cysteine derivative. It is a conjugate acid of a glutathionate(1-).
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Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It is also important as a hydrophilic molecule that is added to lipophilic toxins and waste in the liver during biotransformation before they can become part of the bile. Glutathione is also needed for the detoxification of methylglyoxal, a toxin produced as a by-product of metabolism. This detoxification reaction is carried out by the glyoxalase system. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. GSH is known as a cofactor in both conjugation reactions and reduction reactions, catalyzed by glutathione S-transferase enzymes in cytosol, microsomes, and mitochondria. However, it is capable of participating in non-enzymatic conjugation with some chemicals, as it is hypothesized to do to a significant extent with n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450 reactive metabolite formed by toxic overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein sulfhydryl groups which would otherwise be toxically adducted. The preferred medical treatment to an overdose of this nature, whose efficacy has been consistently supported in literature, is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and allow a usable GSH pool.
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For nutritional supplementation, also for treating dietary shortage or imbalance
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V - Various Research suggests that glutathione is not orally bioactive, and that very little of oral glutathione tablets or capsules is actually absorbed by the body. Glutathione (GSH) participates in leukotriene synthesis and is a cofactor for the enzyme glutathione peroxidase. It also plays a role in the hepatic biotransformation and detoxification process; it acts as a hydrophilic molecule that is added to other lipophilic toxins or wastes prior to entering biliary excretion. It participates in the detoxification of methylglyoxal, a toxic by-product of metabolism, mediated by glyoxalase enzymes. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. Glyoxalase I catalyzes the conversion of methylglyoxal and reduced glutathione to S-D-Lactoyl-glutathione. Glyoxalase II catalyzes the conversion of S-D-Lactoyl Glutathione to Reduced Glutathione and D-lactate. GSH is a cofactor of conjugation and reduction reactions that are catalyzed by glutathione S-transferase enzymes expressed in the cytosol, microsomes, and mitochondria. However, it is capable of participating in non-enzymatic conjugation with some chemicals, as it is hypothesized to do to a significant extent with n-acetyl-p-benzoquinone imine (NAPQI), the reactive cytochrome P450 reactive metabolite formed by toxic overdose of acetaminophen. Glutathione in this capacity binds to NAPQI as a suicide substrate and in the process detoxifies it, taking the place of cellular protein sulfhydryl groups which would otherwise be toxically adducted. The preferred medical treatment to an overdose of this nature, whose efficacy has been consistently supported in literature, is the administration (usually in atomized form) of N-acetylcysteine, which is used by cells to replace spent GSSG and allow a usable GSH pool.
| 292.5
| null |
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/124886.sdf
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D00015
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Glutamine
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C5H10N2O3
| 5,961
| 146.14
| -3.1
| 106
| 146
| 3
| 4
|
C(CC(=O)N)C(C(=O)O)N
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L-glutamine is an optically active form of glutamine having L-configuration. It has a role as an EC 1.14.13.39 (nitric oxide synthase) inhibitor, a nutraceutical, a micronutrient, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a glutamine family amino acid, a proteinogenic amino acid, a glutamine and a L-alpha-amino acid. It is a conjugate base of a L-glutaminium. It is a conjugate acid of a L-glutaminate. It is an enantiomer of a D-glutamine. It is a tautomer of a L-glutamine zwitterion.
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Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells. L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress. The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed.
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Used for nutritional supplementation, also for treating dietary shortage or imbalance. Used to reduce the acute complications of sickle cell disease in adult and pediatric patients 5 years of age and older. FDA Label Treatment of sickle cell disease
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Like other amino acids, glutamine is biochemically important as a constituent of proteins. Glutamine is also crucial in nitrogen metabolism. Ammonia (formed by nitrogen fixation) is assimilated into organic compounds by converting glutamic acid to glutamine. The enzyme which accomplishes this is called glutamine synthetase. Glutamine can then be used as a nitrogen donor in the biosynthesis of many compounds, including other amino acids, purines, and pyrimidines. L-glutamine improves nicotinamide adenine dinucleotide (NAD) redox potential. 0RH81L854J GLUTAMINE Established Pharmacologic Class [EPC] - Amino Acid Chemical Structure [CS] - Amino Acids Glutamine is an Amino Acid. GLUTAMINE Amino Acids [CS]; Amino Acid [EPC] L-GLUTAMINE Amino Acids [CS]; Amino Acid [EPC] A - Alimentary tract and metabolism ... Glutamine is a nitrogen donor in metabolic reactions and the main interorgan nitrogen shuttle. As a source of glutamate, it is essential for maintenance of cellular volume, amino acid economy, glutathione, energy, and reducing equivalents. Glutamine is a conditionally essential amino acid, and several limited studies have suggested that metabolic support of catabolic patients with glutamine may improve their condition and speed their recovery. Absorption is efficient and occurs by an active transport mechanism. Tmax is 30 minutes after a single dose. Absorption kinetics following multiple doses has not yet been determined. Primarily eliminated by metabolism. While L-glutamine is filtered though the glomerulus, nearly all is reabsorbed by renal tubules. Volume of distribution is 200 mL/kg after intravenous bolus dose. After an intravenous bolus dose in three subjects, the volume of distribution was estimated to be approximately 200 mL/kg. Following single dose oral administration of glutamine at 0.1 g/kg to six subjects, mean peak blood glutamine concentration was 1028uM (or 150 mcg/mL) occurring approximately 30 minutes after administration. The pharmacokinetics following multiple oral doses have not been adequately characterized. Metabolism is the major route of elimination for glutamine. Although glutamine is eliminated by glomerular filtration, it is almost completely reabsorbed by the renal tubules. Exogenous L-glutamine likely follows the same metabolic pathways as endogenous L-glutamine which is involved in the formation of glutamate, proteins, nucleotides, and amino acid sugars. Glutamine plays an important role in nitrogen homeostasis and intestinal substrate supply. It has been suggested that glutamine is a precursor for arginine through an intestinal-renal pathway involving inter-organ transport of citrulline. The importance of intestinal glutamine metabolism for endogenous arginine synthesis in humans, however, has remained unaddressed. The aim of this study was to investigate the intestinal conversion of glutamine to citrulline and the effect of the liver on splanchnic citrulline metabolism in humans. Eight patients undergoing upper gastrointestinal surgery received a primed continuous intravenous infusion of [2-(15)N]glutamine and [ureido-(13)C-(2)H(2)]citrulline. Arterial, portal venous and hepatic venous blood were sampled and portal and hepatic blood flows were measured. Organ specific amino acid uptake (disposal), production and net balance, as well as whole body rates of plasma appearance were calculated according to established methods. The intestines consumed glutamine at a rate that was dependent on glutamine supply. Approximately 13% of glutamine taken up by the intestines was converted to citrulline. Quantitatively glutamine was the only important precursor for intestinal citrulline release. Both glutamine and citrulline were consumed and produced by the liver, but net hepatic flux of both amino acids was not significantly different from zero. Plasma glutamine was the precursor of 80% of plasma citrulline and plasma citrulline in turn was the precursor of 10% of plasma arginine. In conclusion, glutamine is an important precursor for the synthesis of arginine after intestinal conversion to citrulline in humans. Endogenous glutamine participates in various metabolic activities, including the formation of glutamate, and synthesis of proteins, nucleotides, and amino sugars. Exogenous glutamine is anticipated to undergo similar metabolism. Enterocytes, Hepatic The half life of elimination is 1 h. After an IV bolus dose in three subjects, the terminal half-life of glutamine was approximately 1 hour. Supplemental L-glutamine's possible immunomodulatory role may be accounted for in a number of ways. L-glutamine appears to play a major role in protecting the integrity of the gastrointestinal tract and, in particular, the large intestine. During catabolic states, the integrity of the intestinal mucosa may be compromised with consequent increased intestinal permeability and translocation of Gram-negative bacteria from the large intestine into the body. The demand for L-glutamine by the intestine, as well as by cells such as lymphocytes, appears to be much greater than that supplied by skeletal muscle, the major storage tissue for L-glutamine. L-glutamine is the preferred respiratory fuel for enterocytes, colonocytes and lymphocytes. Therefore, supplying supplemental L-glutamine under these conditions may do a number of things. For one, it may reverse the catabolic state by sparing skeletal muscle L-glutamine. It also may inhibit translocation of Gram-negative bacteria from the large intestine. L-glutamine helps maintain secretory IgA, which functions primarily by preventing the attachment of bacteria to mucosal cells. L-glutamine appears to be required to support the proliferation of mitogen-stimulated lymphocytes, as well as the production of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma). It is also required for the maintenance of lymphokine-activated killer cells (LAK). L-glutamine can enhance phagocytosis by neutrophils and monocytes. It can lead to an increased synthesis of glutathione in the intestine, which may also play a role in maintaining the integrity of the intestinal mucosa by ameliorating oxidative stress. The exact mechanism of the possible immunomodulatory action of supplemental L-glutamine, however, remains unclear. It is conceivable that the major effect of L-glutamine occurs at the level of the intestine. Perhaps enteral L-glutamine acts directly on intestine-associated lymphoid tissue and stimulates overall immune function by that mechanism, without passing beyond the splanchnic bed. The exact mechanism of L-glutamine's effect on NAD redox potential is unknown but is thought to involve increased amounts of reduced glutathione made available by glutamine supplementation. This improvement in redox potential reduces the amount of oxidative damage which sickle red blood cells are more susceptible to. The reduction in cellular damage is thought to reduce chronic hemolysis and vaso-occlusive events. L-glutamine has important functions in regulation of gastrointestinal cell growth, function, and regeneration. Under normal conditions, glutamine concentration is maintained in the body by dietary intake and synthesis from endogenous glutamate. Data from clinical studies indicate that the role of and nutritional requirements for glutamine during catabolic illness, trauma, and infection may differ significantly from the role of and nutritional requirements for glutamine in healthy individuals. Glutamine concentrations decrease and tissue glutamine metabolism increases during many catabolic disease states, and thus glutamine is often considered a "conditionally essential" amino acid.
| 300
| 2.17
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5961.sdf
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D00016
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Serine
|
C3H7NO3
| 5,951
| 105.09
| -3.1
| 83.6
| 72
| 3
| 4
|
C(C(C(=O)O)N)O
|
L-serine is the L-enantiomer of serine. It has a role as a human metabolite, an algal metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite and a mouse metabolite. It is a serine family amino acid, a proteinogenic amino acid, a L-alpha-amino acid and a serine. It is a conjugate base of a L-serinium. It is a conjugate acid of a L-serinate. It is an enantiomer of a D-serine. It is a tautomer of a L-serine zwitterion.
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L-Serine plays a role in cell growth and development (cellular proliferation). The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine. These bases when linked to the phosphate ester of pentose sugars are essential components of DNA and RNA and the end products of energy producing metabolic pathways, ATP and GTP. In addition, L-serine conversion to glycine via this same enzyme provides the one-carbon units necessary for production of the pyrimidine nucleotide, deoxythymidine monophosphate, also an essential component of DNA.
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Used as a natural moisturizing agent in some cosmetics and skin care products.
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Serine is classified as a nutritionally non-essential amino acid. Serine is critical for the production of the body's proteins, enzymes and muscle tissue. Serine is needed for the proper metabolism of fats and fatty acids. It also helps in the production of antibodies. Serine is used as a natural moisturizing agent in some cosmetics and skin care products. The main source of essential amino acids is from the diet, non-essential amino acids are normally synthesize by humans and other mammals from common intermediates. AMINO ACID CLASSED AS NONESSENTIAL FOR MAINTENANCE OF GROWTH IN RATS. SERINE WAS ESSENTIAL FOR OPTIMAL GROWTH OF EMBRYONIC RAT CELLS IN TISSUE CULTURE. SERINE CAN BE REPLACED BY GLYOXYLIC ACID BUT NOT BY GLYCINE OR GLYCOLIC ACID. IN PT AGE 2-9 YR, SERINE PRESENT IN ACID MUCOPOLYSACCHARIDES. EXCESSIVE ACCUMULATION & EXCRETION IN URINE OF MUCOPOLYSACCHARIDES MAY BE RELATED TO ABNORMAL BONDING BETWEEN MUCOPOLYSACCHARIDES & PROTEIN. IN PT AGE 2-9 YR, URINARY SERINE EXCRETION INCR FROM 0.059-0.162 UMOL/24 HR & PLASMA SERINE LEVELS INCR FROM 0.102-0.158 UMOL/ML. IN PT AGE 2-9 YR, SERINE IS PROBABLY NOT ESTERIFIED THROUGH ITS BETA-HYDROXYL GROUP TO ACID MUCOPOLYSACCHARIDES BUT IS LINKED BY CARBOXYL GROUP. DETERMINATION OF SERINE LEVELS IN 13 REGIONS OF THE RAT CEREBRAL CORTEX FAILED TO SHOW ANY MARKED DIFFERENCES IN THE AMINO ACID CONTENTS OF CORTEX AREAS OF DIVERSE FUNCTIONS. L-Serine plays a role in cell growth and development (cellular proliferation). The conversion of L-serine to glycine by serine hydroxymethyltransferase results in the formation of the one-carbon units necessary for the synthesis of the purine bases, adenine and guanine. These bases when linked to the phosphate ester of pentose sugars are essential components of DNA and RNA and the end products of energy producing metabolic pathways, ATP and GTP. In addition, L-serine conversion to glycine via this same enzyme provides the one-carbon units necessary for production of the pyrimidine nucleotide, deoxythymidine monophosphate, also an essential component of DNA.
| null | 2.21
|
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5951.sdf
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D00017
|
Formaldehyde
|
CH2O
| 712
| 30.026
| 1.2
| 17.1
| 2
| 0
| 1
|
C=O
|
At room temperature, formaldehyde is a colorless, flammable gas that has a distinct, pungent smell. It is also known as methanal, methylene oxide, oxymethyline, methylaldehyde, and oxomethane. Formaldehyde is naturally produced in small amounts in our bodies. It is used in the production of fertilizer, paper, plywood, and urea-formaldehyde resins. It is also used as a preservative in some foods and in many products used around the house, such as antiseptics, medicines, and cosmetics.
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IDENTIFICATION AND USE: Formaldehyde is a clear, water-white, very slightly acid, gas or liquid. It is registered for pesticide use in the U.S. but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. Formaldehyde is used primarily as a fumigant in agricultural premises such as poultry and swine farms and processing plants as well as in citrus packing and mushroom houses. It is used as a hard surface disinfectant in commercial premises, industrial premises and veterinary clinics. Formaldehyde is also registered as a materials preservative for consumer products such as laundry detergents, general purpose cleaners and wall paper adhesives. There are no inert ingredient uses for this chemical. It is also used as an antimicrobial in biologics, topicals, hepatitis B vaccine, sterilizer for kidney dialysis membranes. Additional uses of formaldehyde in medicine include disinfecting hospital wards, preserving specimens, and as a disinfectant against athlete's foot. HUMAN EXPOSURE AND TOXICITY: Acute effects of airborne formaldehyde exposure: Odor detection, 0.05-1.0 ppm; Eye irritation, 0.01-2 ppm; Upper respiratory tract irritation (e.g., irritation of the nose or throat), 0.10-11 ppm; Lower airway irritation (e.g., cough, chest tightness, and wheezing), 5-30 ppm; Pulmonary edema, inflammation, pneumonia, 50-100 ppm; Death >100 ppm. Formaldehyde can provoke skin reactions in sensitized subjects, not only by contact but also by inhalation. According to IARC, there is sufficient evidence in humans for the carcinogenicity of formaldehyde. Formaldehyde causes cancer of the nasopharynx and leukemia. Also, a positive association has been observed between exposure to formaldehyde and sinonasal cancer. An investigation of reproductive function in female workers exposed to formaldehyde in the garment industry revealed increased incidence of menstrual disorders, inflammatory disease of the reproductive tract, sterility, anemia, and low birth weights among offspring. The published studies suggest that inhalation of formaldehyde leads to increased micronuclei frequencies in nasal and/or buccal mucosa cells. ANIMAL STUDIES: Acute effects in rats to low (<1 ppm) or moderate (10-50 ppm) of vapor resulted in increased airway resistance, decreased sensitivity of nasopalatine nerve, irritation of eyes and of respiratory system, and changes in hypothalamus. Exposure to high doses (above 100 ppm) caused salivation, acute dyspnea, vomiting, cramps and death. Hair depigmentation was observed in black mice at site of sc injection of 100 ug formaldehyde. Mice treated with formaldehyde on skin developed severe liver damage. Groups of 25 mated female rats were exposed by inhalation to formaldehyde (0, 2, 5 or 10 ppm (2.5, 6.2 or 12.3 mg/cu m) for 6 hr per day on days 6-15 of gestation. At 10 ppm, there was a significant decrease in maternal food consumption and weight gain. None of the parameters of pregnancy, including numbers of corpora lutea, implantation sites, live fetuses, dead fetuses and resorptions or fetal weights, were affected by treatment. An increased incidence of reduced ossification was observed at 5 and 10 ppm in the absence of maternal toxicity (10 ppm). Formaldehyde caused nasal squamous cell carcinomas in the rat following 2 year inhalation exposure. The incidence of this tumor in a historical data base of 16,794 rats was nil, indicating that it is a rare spontaneous tumor. Male and female rats of different ages at the start of the experiments (12 day embryos, and 7 and 25 weeks old) were administered formaldehyde in drinking water at different doses (2,500 or 1,500, 1,000, 500, 100, 50, 10, 0 ppm). An increased incidence of leukemias and of gastro-intestinal tumors was observed in formaldehyde treated rats. Gastro-intestinal tumors are exceptionally rare in the rats of the colony used. Formaldehyde induces gene mutation in bacteria, fungi, yeast, and Drosophila larvae as well as in cultured rodent and human cells. In part, these mutations appear to be the consequence of DNA damage. A second mechanism by which formaldehyde may damage the genome is inhibition of DNA repair. ECOTOXICITY STUDIES: It was concluded from the study that formalin feeding to female quails at 2.5 mL/kg feed is without harmful effects, however, higher doses are not without health risks.
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Use for drying skin before or after surgical removal of warts or where dryness is required.
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Substances used on inanimate objects that destroy harmful microorganisms or inhibit their activity. Disinfectants are classed as complete, destroying SPORES as well as vegetative forms of microorganisms, or incomplete, destroying only vegetative forms of the organisms. They are distinguished from ANTISEPTICS, which are local anti-infective agents used on humans and other animals. (From Hawley's Condensed Chemical Dictionary, 11th ed) (See all compounds classified as Disinfectants.) Agents employed in the preparation of histologic or pathologic specimens for the purpose of maintaining the existing form and structure of all of the constituent elements. Great numbers of different agents are used; some are also decalcifying and hardening agents. They must quickly kill and coagulate living tissue. (See all compounds classified as Fixatives.) 1HG84L3525 FORMALDEHYDE Established Pharmacologic Class [EPC] - Standardized Chemical Allergen Physiologic Effects [PE] - Increased Histamine Release Physiologic Effects [PE] - Cell-mediated Immunity Chemical Structure [CS] - Allergens Formaldehyde is a Standardized Chemical Allergen. The physiologic effect of formaldehyde is by means of Increased Histamine Release, and Cell-mediated Immunity. FORMALDEHYDE Increased Histamine Release [PE]; Cell-mediated Immunity [PE]; Allergens [CS]; Standardized Chemical Allergen [EPC] Formaldehyde is absorbed readily from the respiratory and oral tracts and, to a much lesser degree, from the skin. It is the simplest aldehyde and reacts readily with macromolecules, such as proteins and nucleic acids. Inhalational exposure has been reported to result in almost complete absorption. Dermal absorption due to contact with formaldehyde-containing materials (e.g., textiles, permanent-press clothing, cosmetics, or other materials) is of low order of magnitude. ... Formaldehyde normally is converted and excreted as carbon dioxide in the air, as formic acid in the urine, or as one of many breakdown products from one-carbon pool metabolism. As a result of rapid absorption by both the oral and inhalational routes and its rapid metabolism, little or no formaldehyde is excreted unmetabolized. In rats exposed to (14)C-formaldehyde by inhalation, 40% of the radiolabel was excreted in the air and 20% in the urine and feces, whereas 40% remained in the carcass. In rats and mice administered (14)C-formaldehyde intragastrically, 40% of dose... /was/ expired as carbon dioxide, 10% /was/ excreted in urine and 1% in feces after 12 hr; carcasses contained 20% after 24 hr and 10% after 4 days. When female rats were administered (14)C-formaldehyde ip at dose level of 70 mg/kg, 82% of dose was expired as (14)C dioxide and 13-14% was excreted via kidneys... . Formaldehyde is absorbed rapidly and almost completely from the rodent intestinal tract. In rats, about 40% of an oral dose of (14)C-formaldehyde (7 mg/kg) was eliminated as (14)C-carbon dioxide within 12 hours, while 10% was excreted in the urine and 1% in the feces. A substantial portion of the radioactivity remained in the carcass as products of metabolic incorporation. Four men and two women were exposed to a 1.9 ppm air concentration of formaldehyde in a large walk-in chamber for 40 minutes. Shortly before and shortly after the exposure, venous blood samples were taken from each person (each person served as his/her own control) and the blood was analyzed for formaldehyde content. Mean venous blood formaldehyde concentrations in humans prior to exposure showed a blood concentration of 2.61 + or - 0.41 ug/g of blood. Individual variability was markedly present. Immediately after a 40-minute exposure, mean blood concentration of formaldehyde was 2.77 + or - 0.28 ug/g of blood. There was no significant difference between pre- and postexposure blood concentrations of formaldehyde at the formaldehyde air concentrations tested in this study. This result suggests that formaldehyde was absorbed only into the tissues of the respiratory tract. The absence of increased formaldehyde concentrations in the blood is likely due to its rapid metabolism in these tissues and/or fast reaction with cellular macromolecules. For more Absorption, Distribution and Excretion (Complete) data for FORMALDEHYDE (13 total), please visit the HSDB record page. When female rats were administered (14)C-formaldehyde ip at dose level of 70 mg/kg, 82% of dose was expired as (14)carbon dioxide and 13-14% was excreted via kidneys in form of methionine, serine, and formaldehyde-cysteine adduct. Rats injected ip with 0.26 mg/kg (14)C-labeled formaldehyde ... excreted approx 22% of this dose in the urine over 5 days. Formic acid and a thiazolidine-4-carboxylic acid derivative were identified in urine as formaldehyde metabolites. Several of the urinary excretion products of formaldehyde in rats have been identified after intraperitoneal administration of (14)C-formaldehyde. After injecting Wistar rats with 0.26 mg/kg body weight, ... formate and a sulfur-containing metabolite (thought to be a derivative of thiazolidine-4-carboxylic acid) and products presumed to result from one-carbon metabolism /were detected/. Thiazolidine-4-carboxylate, which is formed via the nonenzymatic condensation of formaldehyde with cysteine, was not detected in urine. Formaldehyde absorbed into the bloodstream is metabolized to formic acid, which is excreted in the urine as the sodium salt or oxidized further to carbon dioxide and water. This detoxification process can deal efficiently with low concentrations of formaldehyde, but high concentrations cause acidosis and tissue damage. For more Metabolism/Metabolites (Complete) data for FORMALDEHYDE (13 total), please visit the HSDB record page. Formaldehyde may be absorbed following inhalation, oral, or dermal exposure. It is an essential metabolic intermediate in all cells and is produced during the normal metabolism of serine, glycine, methionine, and choline and also by the demethylation of N-, S-, and O-methyl compounds. Exogenous formaldehyde is metabolized to formate by the enzyme formaldehyde dehydrogenase at the initial site of contact. After oxidation of formaldehyde to formate, the carbon atom is further oxidized to carbon dioxide or incorporated into purines, thymidine, and amino acids via tetrahydrofolatedependent one-carbon biosynthetic pathways. Formaldehyde is not stored in the body and is excreted in the urine (primarily as formic acid), incorporated into other cellular molecules, or exhaled as carbon dioxide. (L962) Urine (for formic acid): 80-90 minutes; [TDR, p. 713] ...In several species... formaldehyde has a half-life of only 1 min; but the half-life for formic acid is species dependent. Formaldehyde is rapidly metabolized with a half-life in the blood of approx 1.5 min. This half-life is based primarily on primate data although available human data are consistent with this observation of a very short half-life. Data from other species suggest that the half-life of formaldehyde is fairly similar in many species. Formaldehyde is thought to act via sensory nerve fibers that signal through the trigeminal nerve to reflexively induce bronchoconstriction through the vagus nerve. Exposure to formaldehyde, a known air toxic, is associated with cancer and lung disease. Despite the adverse health effects of formaldehyde, the mechanisms underlying formaldehyde-induced disease remain largely unknown. Research has uncovered microRNAs (miRNAs) as key posttranscriptional regulators of gene expression that may influence cellular disease state. Although studies have compared different miRNA expression patterns between diseased and healthy tissue, this is the first study to examine perturbations in global miRNA levels resulting from formaldehyde exposure. We investigated whether cellular miRNA expression profiles are modified by formaldehyde exposure to test the hypothesis that formaldehyde exposure disrupts miRNA expression levels within lung cells, representing a novel epigenetic mechanism through which formaldehyde may induce disease. Human lung epithelial cells were grown at air-liquid interface and exposed to gaseous formaldehyde at 1 ppm for 4 hr. Small RNAs and protein were collected and analyzed for miRNA expression using microarray analysis and for interleukin (IL-8) protein levels by enzyme-linked immunosorbent assay (ELISA). RESULTS: Gaseous formaldehyde exposure altered the miRNA expression profiles in human lung cells. Specifically, 89 miRNAs were significantly down-regulated in formaldehyde-exposed samples versus controls. Functional and molecular network analysis of the predicted miRNA transcript targets revealed that formaldehyde exposure potentially alters signaling pathways associated with cancer, inflammatory response, and endocrine system regulation. IL-8 release increased in cells exposed to formaldehyde, and results were confirmed by real-time polymerase chain reaction. Formaldehyde alters miRNA patterns that regulate gene expression, potentially leading to the initiation of a variety of diseases. Formaldehyde at high concentrations is a contributor to air pollution. It is also an endogenous metabolic product in cells, and when beyond physiological concentrations, has pathological effects on neurons. Formaldehyde induces mis-folding and aggregation of neuronal tau protein, hippocampal neuronal apoptosis, cognitive impairment and loss of memory functions, as well as excitation of peripheral nociceptive neurons in cancer pain models. Intracellular calcium ([Ca(2+)](i)) is an important intracellular messenger, and plays a key role in many pathological processes. The present study aimed to investigate the effect of formaldehyde on [Ca(2+)](i) and the possible involvement of N-methyl-D-aspartate receptors (NMDARs) and T-type Ca(2+) channels on the cell membrane. METHODS: Using primary cultured hippocampal neurons as a model, changes of [Ca(2+)](i) in the presence of formaldehyde at a low concentration were detected by confocal laser scanning microscopy. Formaldehyde at 1 mmol/L approximately doubled [Ca(2+)](i). (2R)-amino-5-phosphonopentanoate (AP5, 25 umol/L, an NMDAR antagonist) and mibefradil (MIB, 1 umol/L, a T-type Ca(2+) channel blocker), given 5 min after formaldehyde perfusion, each partly inhibited the formaldehyde-induced increase of [Ca(2+)](i), and this inhibitory effect was reinforced by combined application of AP5 and MIB. When applied 3 min before formaldehyde perfusion, AP5 (even at 50 umol/L) did not inhibit the formaldehyde-induced increase of [Ca(2+)](i), but MIB (1 umol/L) significantly inhibited this increase by 70%. These results suggest that formaldehyde at a low concentration increases [Ca(2+)](i) in cultured hippocampal neurons; NMDARs and T-type Ca(2+) channels may be involved in this process. /The purpose of this study was/ to study the role of poly (ADP-ribose) polymerase-l (PARP-1) in formaldehyde-induced DNA damage response in human bronchial epithelial (HBE) cells and to investigate the mechanism of formaldehyde carcinogenicity. The protein levels were measured by Western blot. The interaction between different proteins was determined by co-immunoprecipitation assay. The chemical inhibitor was used to confirm the relationship between PARP-1 and DNA damage repair. After being exposed to different concentrations of formaldehyde for 4 hr, HBE cells showed no significant changes in cell viability. Cell viability was significantly reduced after 24-hr exposure to 80 and 160 umol/L formaldehyde (P < 0.05). The 10 umol/L formaldehyde resulted in significant increases in the protein levels of PARP-1 and XRCC-1. However, 80 umol/L formaldehyde led to a significant decrease in the protein level of PARP-1 of 124 KD molecular weight but a significant increase in the protein level of PARP-1 of 89 KD molecular weight; there was no significant change in the protein level of XRCC-1. The co-immunoprecipitation assay showed that 10 umol/L formaldehyde induced increased binding between PARP-1 and XRCC-1, but 80 umol/L formaldehyde led to no significant change in binding between PARP-1 and XRCC-1. Here, we confirmed the role of 10 umol/L formaldehyde in strand breaks by comet assay which showed an increase in the tail DNA content of HBE cells after 4-h formaldehyde exposure. No significant difference was observed in tail DNA content between treated HBE cells and control cells at 2 h after formaldehyde was removed. Moreover, compared with control, inhibition of PARP-1 induced a significant increase in tail DNA content, and a significant difference was observed in tail DNA content between inhibited HBE cells and control cells at 2 h after formaldehyde was removed. Inhibition of PARP-1 significantly reduced DNA repair capacity. PARP-1 mediated the repair of DNA damage induced by low-concentration formaldehyde through recruiting XRCC-1 protein, and may be involved in the regulation of cell apoptosis induced by high-concentration formaldehyde. Peroxiredoxin 2 (Prx2), a member of the peroxiredoxin family, regulates numerous cellular processes through intracellular oxidative signal transduction pathways. Formaldehyde (FA)-induced toxic damage involves reactive oxygen species (ROS) that trigger subsequent toxic effects and inflammatory responses. The present study aimed to investigate the role of Prx2 in the development of bone marrow toxicity caused by FA and the mechanism underlying FA toxicity. According to the results of the preliminary investigations, the mice were divided into four groups (n=6 per group). One group was exposed to ambient air and the other three groups were exposed to different concentrations of FA (20, 40, 80 mg/cu m) for 15 days in the respective inhalation chambers, for 2 hr a day. At the end of the 15-day experimental period, all of the mice were sacrificed and bone marrow cells were obtained. Cell samples were used for the determination of pathology, glutathione peroxidase (GSH-Px) activity and myeloperoxidase (MPO) activity and protein expression; as well as for the determination of DNA damage and Prx2 expression. The results revealed an evident pathological change in the FA-treated groups, as compared with the controls. In the FA treatment group GSH-Px activity was decreased, while MPO activity and protein expression were increased. The rate of micronucleus and DNA damage in the FA-treated groups was also increased and was significantly different compared with the control, while the expression of Prx2 was decreased. The present study suggested that at certain concentrations, FA had a toxic effect on bone marrow cells and that changes in the Prx2 expression are involved in this process.
| null | 13.3
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/712.sdf
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D00019
|
Methionine
|
C5H11NO2S
| 6,137
| 149.21
| -1.9
| 88.6
| 97
| 2
| 4
|
CSCCC(C(=O)O)N
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Minute hexagonal plates from dilute alcohol. (NTP, 1992)
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The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability.
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Used for protein synthesis including the formation of SAMe, L-homocysteine, L-cysteine, taurine, and sulfate.
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L-Methionine is a principle supplier of sulfur which prevents disorders of the hair, skin and nails; helps lower cholesterol levels by increasing the liver's production of lecithin; reduces liver fat and protects the kidneys; a natural chelating agent for heavy metals; regulates the formation of ammonia and creates ammonia-free urine which reduces bladder irritation; influences hair follicles and promotes hair growth. L-methionine may protect against the toxic effects of hepatotoxins, such as acetaminophen. Methionine may have antioxidant activity. V - Various Plays an important role in biological methylation. Both l- and d-forms are effective in rat and man. D-form undergoes deamination, and the keto compound is then transaminated with the resultant inversion of the natural l-form. Methionine restriction (MR) limits age-related adiposity in Fischer 344 (F344) rats. To assess the mechanism of adiposity resistance, the effect of MR on adipose tissue (AT) 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1) was examined. MR induced 11beta-HSD1 activity in all ATs, correlating with increased tissue corticosterone. However, an inverse relationship between 11beta-HSD1 activity and adipocyte size was observed. Because dietary restriction controls lipogenic and lipolytic rates, MR's effects on lipogenic and lipolytic enzymes were evaluated. MR increased adipose triglyceride lipase and acetyl-coenzyme A carboxylase (ACC) protein levels but induced ACC phosphorylation at serine residues that render the enzyme inactive, suggesting alterations of basal lipolysis and lipogenesis. In contrast, no changes in basal or phosphorylated hormone-sensitive lipase levels were observed. ACC-phosphorylated sites were specific for AMP-activated protein kinase (AMPK); therefore, AMPK activation was evaluated. Significant differences in AMPKalpha protein, phosphorylation, and activity levels were observed only in retroperitoneal fat from MR rats. No differences in protein kinase A phosphorylation and intracellular cAMP levels were detected. In vitro studies revealed increased lipid degradation and a trend toward increased lipid synthesis, suggesting the presence of a futile cycle. In conclusion, MR disrupts the lipogenic/lipolytic balance, contributing importantly to adiposity resistance in F344 rats. The methionine choline-deficient (MCD) diet results in liver injury similar to human nonalcoholic steatohepatitis (NASH). The aims of this study were to define mechanisms of MCD-induced steatosis in insulin-resistant db/db and insulin-sensitive db/m mice. MCD-fed db/db mice developed more hepatic steatosis and retained more insulin resistance than MCD-fed db/m mice. Both subcutaneous and gonadal fat were reduced by MCD feeding: gonadal fat decreased by 23% in db/db mice and by 90% in db/m mice. Weight loss was attenuated in the db/db mice, being only 13% compared with 35% in MCD-fed db/db and db/m mice, respectively. Both strains had upregulation of hepatic fatty acid transport proteins as well as increased hepatic uptake of [14C]oleic acid: 3-fold in db/m mice (P < 0.001) and 2-fold in db/db mice (P < 0.01) after 4 weeks of MCD feeding. In both murine strains, the MCD diet reduced triglyceride secretion and downregulated genes involved in triglyceride synthesis. Therefore, increased fatty acid uptake and decreased VLDL secretion represent two important mechanisms by which the MCD diet promotes intrahepatic lipid accumulation in this model... In women whose average daily intake of methionine was above the lowest quartile of intake (greater than 1.34 g/day), a 30 to 40% reduction in neural tube defect-affected pregnancies was observed. These reductions were observed for both anencephaly and spina bifida. For more Bionecessity (Complete) data for (L)-Methionine (20 total), please visit the HSDB record page. Absorbed from the lumen of the small intestine into the enterocytes by an active transport process. ... Rats were fed diets containing [(14)C-methyl]l-methionine ... with 6% of sodium formate, and conversion of (14)C into [(14)C]formate was measured in urine and exhaled air (as (14)CO2) ... Total oxidation of [(14)C-methyl] into CO2, amounted to 60-87% for methionine ... Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. ... Although the plasma compartment is most easily sampled, the concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools. /Amino acids/ After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bond-specific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. /Amino acids/ Protein secretion into the intestine continues even under conditions of protein-free feeding, and fecal nitrogen losses (ie, nitrogen lost as bacteria in the feces) may account for 25% of the obligatory loss of nitrogen. Under this dietary circumstance, the amino acids secreted into the intestine as components of proteolytic enzymes and from sloughed mucosal cells are the only sources of amino acids for the maintenance of the intestinal bacterial biomass. ... Other routes of loss of intact amino acids are via the urine and through skin and hair loss. These losses are small by comparison with those described above, but nonetheless may have a significant impact on estimates of requirements, especially in disease states. /Amino acids/ For more Absorption, Distribution and Excretion (Complete) data for (L)-Methionine (11 total), please visit the HSDB record page. Hepatic Product of oxidative deamination or transamination--alpha-keto-gamma-methiolbutyric acid. /From table/ ... Oxidation of methionine (S-methyl-l-cysteine and sarcosine) methyl group in vivo proceeds primarily by way of free formate, and that conversion to formate is probably not catalysed by tetrahydrofolic acid. ... Methionine ... is catabolized to a large extent independently of initial activation to S-adenosyl-l-methionine. The system for catabolism ... appears analogous to one that catalyses oxidation of S-methyl-l-cysteine methyl group ... The methyl group of methionine ... /has been/ shown ... to yield formate in vitro and in vivo. Infants more rapidly metabolized methionine than adults. For more Metabolism/Metabolites (Complete) data for (L)-Methionine (7 total), please visit the HSDB record page. Hepatic The mechanism of the possible anti-hepatotoxic activity of L-methionine is not entirely clear. It is thought that metabolism of high doses of acetaminophen in the liver lead to decreased levels of hepatic glutathione and increased oxidative stress. L-methionine is a precursor to L-cysteine. L-cysteine itself may have antioxidant activity. L-cysteine is also a precursor to the antioxidant glutathione. Antioxidant activity of L-methionine and metabolites of L-methionine appear to account for its possible anti-hepatotoxic activity. Recent research suggests that methionine itself has free-radical scavenging activity by virtue of its sulfur, as well as its chelating ability. Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Protein synthesis/ The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. /Protein degradation/ Methionine dependence, the inability of cells to grow when the amino acid methionine is replaced in culture medium by its metabolic precursor homocysteine, is characteristic of many cancer cell lines and some tumors in situ. Most cell lines proliferate normally under these conditions. The methionine dependent tumorigenic human melanoma cell line MeWo-LC1 was derived from the methionine independent non-tumorigenic line, MeWo. MeWo-LC1 has a cellular phenotype identical to that of cells from patients with the cblC inborn error of cobalamin metabolism, with decreased synthesis of cobalamin coenzymes and decreased activity of the cobalamin-dependent enzymes methionine synthase and methylmalonylCoA mutase. Inability of cblC cells to complement the defect in MeWo-LC1 suggested that it was caused by decreased activity of the MMACHC gene. However, no potentially disease causing mutations were detected in the coding sequence of MMACHC in MeWo-LC1. No MMACHC expression was detected in MeWo-LC1 by quantitative or non-quantitative PCR. There was virtually complete methylation of a CpG island at the 5'-end of the MMACHC gene in MeWo-LC1, consistent with inactivation of the gene by methylation. The CpG island was partially methylated (30-45%) in MeWo and only lightly methylated (2-11%) in control fibroblasts. Infection of MeWo-LC1 with wild type MMACHC resulted in correction of the defect in cobalamin metabolism and restoration of the ability of cells to grow in medium containing homocysteine. /It was concluded/ that epigenetic inactivation of the MMACHC gene is responsible for methionine dependence in MeWo-LC1.
| null | 2.28
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/6137.sdf
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D00020
|
Tryptophan
|
C11H12N2O2
| 6,305
| 204.22
| -1.1
| 79.1
| 245
| 3
| 3
|
C1=CC=C2C(=C1)C(=CN2)CC(C(=O)O)N
|
L-tryptophan is a white powder with a flat taste. An essential amino acid; occurs in isomeric forms. (NTP, 1992)
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A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD<sup>+</sup> and NADP<sup>+</sup>.
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Tryptophan may be useful in increasing serotonin production, promoting healthy sleep, managing depression by enhancing mental and emotional well-being, managing pain tolerance, and managing weight.
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Tryptophan is critical for the production of the body's proteins, enzymes and muscle tissue. It is also essential for the production of niacin, the synthesis of the neurotransmitter serotonin and melatonin. Tryptophan supplements can be used as natural relaxants to help relieve insomnia. Tryptophan can also reduce anxiety and depression and has been shown to reduce the intensity of migraine headaches. Other promising indications include the relief of chronic pain, reduction of impulsivity or mania and the treatment of obsessive or compulsive disorders. Tryptophan also appears to help the immune system and can reduce the risk of cardiac spasms. Tryptophan deficiencies may lead to coronary artery spasms. Tryptophan is used as an essential nutrient in infant formulas and intravenous feeding. Tryptophan is marketed as a prescription drug (Tryptan) for those who do not seem to respond well to conventional antidepressants. It may also be used to treat those afflicted with seasonal affective disorder (a winter-onset depression). Tryptopan serves as the precursor for the synthesis of serotonin (5-hydroxytryptamine, 5-HT) and melatonin (N-acetyl-5-methoxytryptamine). A structurally and mechanistically diverse group of drugs that are not tricyclics or monoamine oxidase inhibitors. The most clinically important appear to act selectively on serotonergic systems, especially by inhibiting serotonin reuptake. (See all compounds classified as Antidepressive Agents, Second-Generation.) N - Nervous system ... Skin is an optically inhomogeneous medium; reflection, refraction, scattering, and absorption all modify the radiation that reaches deeper structures. Important UV absorbers within the epidermis incl melanin, which varies greatly in content and location between individuals and races; urocanic acid, a deamination product of histidine found in sweat; and for shorter wavelengths, proteins containing tryptophan and tyrosine. The net optical effect is that shorter wavelengths are selectively absorbed in the superficial layers, although a biologically significant amt of UV-B reaches the dermis ... . An essential amino acid for human development; precursor of serotonin. ...Tryptophan is a significant precursor of niacin for humans. It is for this reason that high corn diets result in clinical deficiency (pellagra) of niacin, corn being particularly deficient in tryptophan. Corn and cereal grains contain fairly adequate quantities of niacin, but the vitamin is in a bound and unavailable form. They are also low in tryptophan. The combination of low tryptophan and unavailable dietary niacin results in a niacin deficiency. In current feeding practice in intensive agriculture situations, niacin or tryptophan should be added to high-concentrate diets of poultry and pigs. For more Bionecessity (Complete) data for (L)-Tryptophan (30 total), please visit the HSDB record page. (L)-Tryptophan with plant oils in soft gelatin capsules permitted lower dosage than with usual dosage form. Max of free tryptophan in serum was achieved in 1st hr whereas 4-5 times as much would be required with tablets or hard gelatin capsules. Absorption and Fate. Tryptophan is readily absorbed from the gastro-intestinal tract. Tryptophan is extensively bound to serum albumin. It is metabolized to serotonin and other metabolites, incl kynurenine derivatives, and excreted in the urine. Pyridoxine and ascorbic acid appear to be concerned in its metabolism. Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. ... Although the plasma compartment is most easily sampled, the concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools. /Amino acids/ After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bond-specific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. /Amino acids/ For more Absorption, Distribution and Excretion (Complete) data for (L)-Tryptophan (9 total), please visit the HSDB record page. Hepatic. In Hartnup disease ... tryptophane appear/s/ in urine due to defective renal and intestinal absorption of tryptophane ... It is an intermediary metabolite in the synthesis of serotonin (5-hydroxytryptamine) and 5-hydroxyindole acetic acid (HIAA). Patients with bladder cancer excreted significantly more kynurenic acid, acetylkynurenine, kynurenine, and 3-hydroxykynurenine after ingesting a loading dose of L-tryptophan than did control subjects with no known disease. Tryptophan is metabolized in the liver by tryptophan pyrrolase and tryptophan hydroxylase. Metabolites include hydroxytryptophan, which is then converted to serotonin, and kynurenine derivatives. Some tryptophan is converted to nicotinic acid and nicotinamide. Pyridoxine and ascorbic acid are cofactors in the decarboxylation and hydroxylation, respectively, of tryptophan; pyridoxine apparently prevents the accumulation of the kynurenine metabolites. Yields indole-3-pyruvic acid in man ... and in rats; yields tryptamine in guinea pigs. /From table/ For more Metabolism/Metabolites (Complete) data for (L)-Tryptophan (21 total), please visit the HSDB record page. Hepatic. The biological half-life of tryptophan was reported to be 15.8 hr. A number of important side reactions occur during the catabolism of tryptophan on the pathway to acetoacetate. The first enzyme of the catabolic pathway is an iron porphyrin oxygenase that opens the indole ring. The latter enzyme is highly inducible, its concentration rising almost 10-fold on a diet high in tryptophan. Kynurenine is the first key branch point intermediate in the pathway. Kynurenine undergoes deamniation in a standard transamination reaction yielding kynurenic acid. Kynurenic acid and metabolites have been shown to act as antiexcitotoxics and anticonvulsives. A second side branch reaction produces anthranilic acid plus alanine. Another equivalent of alanine is produced further along the main catabolic pathway, and it is the production of these alanine residues that allows tryptophan to be classified among the glucogenic and ketogenic amino acids. The second important branch point converts kynurenine into 2-amino-3-carboxymuconic semialdehyde, which has two fates. The main flow of carbon elements from this intermediate is to glutarate. An important side reaction in liver is a transamination and several rearrangements to produce limited amounts of nicotinic acid, which leads to production of a small amount of NAD<sup>+</sup> and NADP<sup>+</sup>. Findings indicate that enhanced rates of serotonin turnover produced by (L)-tryptophan and physical restraint are associated with inhibition of thyroid-stimulating hormone (TSH) and stimulation of prolactin release from anterior pituitary in rats. L-Tryptophan, an indispensable amino acid, serves as a precursor for several small molecules of functional significance including the vitamin niacin, the neurotransmitter serotonin, the metabolite tryptamine, and the pineal hormone melatonin. Increases in tryptophan have been shown to increase synthesis of the neurotransmitters in brain, blood, and other body organs. Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Amino acids/ The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. For more Mechanism of Action (Complete) data for (L)-Tryptophan (7 total), please visit the HSDB record page.
| 5
| 2.36
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/6305.sdf
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D00021
|
Phenylalanine
|
C9H11NO2
| 6,140
| 165.19
| -1.5
| 63.3
| 153
| 2
| 3
|
C1=CC=C(C=C1)CC(C(=O)O)N
|
L-phenylalanine is an odorless white crystalline powder. Slightly bitter taste. pH (1% aqueous solution) 5.4 to 6. (NTP, 1992)
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Extremely high serum levels of phenylalanine are found in patients with the inborn error of metabolism (IEM) called Phenylketonuria (PKU). At pathological concentrations typical of PKU, phenylalanine self-assembles into fibrils with amyloid-like morphology and well-ordered electron diffraction. These fibrils and their resulting amyloid deposits that localize to the brain appear to be partially responsible for the neural tissue damage seen in PKU patients (A8160). It has also been suggested that very high plasma phenylalanine concentrations can increase phenylalanine entry into brain and thereby restrict the entry of other large neutral amino acids. The lack of large neutral amino acids may lead to disturbed cerebral protein synthesis, which is particularly important for young children (A8162). The mechanism of L-phenylalanine's putative antidepressant activity may be accounted for by its precursor role in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects. <br/>The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin.
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L-phenylalanine may be helpful in some with depression. It may also be useful in the treatment of vitiligo. There is some evidence that L-phenylalanine may exacerbate tardive dyskinesia in some schizophrenic patients and in some who have used neuroleptic drugs.
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Used by the brain to produce Norepinephrine, a chemical that transmits signals between nerve cells and the brain; keeps you awake and alert; reduces hunger pains; functions as an antidepressant and helps improve memory. Essential amino acid for human development. Older views of the nutritional classification of amino acids categorized them into two groups: indispensable (essential) and dispensable (nonessential). The nine indispensable amino acids /(histidine, isoleucine, leucine, lysine, methionine, phenylalanine, threonine, tryptophan, and valine)/ are those that have carbon skeletons that cannot be synthesized to meet body needs from simpler molecules in animals, and therefore must be provided in the diet. ...The definition of dispensable amino acids has become blurred as more information on the intermediary metabolism and nutritional characteristics of these compounds has accumulated. ... Dispensable amino acids /have been divided/ into two classes: truly dispensable and conditionally indispensable. Five amino acids /(alanine, aspartic acid, asparagine, glutamic acid, and serine)/ are termed dispensable as they can be synthesized in the body from either other amino acids or other complex nitrogenous metabolites. In addition, six other amino acids, including /arginine, cysteine, glutamine, glycine, proline, and tyrosine/, are conditionally indispensable as they are synthesized from other amino acids or their synthesis is limited under special pathophysiological conditions. This is even more of an issue in the neonate where it has been suggested that only alanine, aspartate, glutamate, serine, and probably asparagine are truly dietarily dispensable. The term conditionally indispensable recognizes the fact that under most normal conditions the body can synthesize these amino acids to meet metabolic needs. However, there may be certain physiological circumstances: prematurity in the young infant where there is an inadequate rate at which cysteine can be produced from methionine; the newborn, where enzymes that are involved in quite complex synthetic pathways may be present in inadequate amounts as in the case of arginine, which results in a dietary requirement for this amino acid; or pathological states, such as severe catabolic stress in an adult, where the limited tissue capacity to produce glutamine to meet increased needs and to balance increased catabolic rates makes a dietary source of these amino acids required to achieve body nitrogen homeostasis. The cells of the small intestine become important sites of conditionally indispensable amino acid, synthesis, with some amino acids (e.g., glutamine and arginine) becoming nutritionally indispensable under circumstances of intestinal metabolic dysfunction. /Amino acids/ When diets high or low in protein are given, there is a gain or loss of body protein over the first few days, before re-equilibration of protein intake with the rates of oxidation and excretion. This phenomenon has led to the concept of a "labile protein reserve," which can be gained or lost from the body as a short-term store for use in emergencies or to take account of day-to-day variations in dietary intake. Studies in animals have suggested that this immediate labile protein store is contained in the liver and visceral tissues, as their protein content decreases very rapidly during starvation or protein depletion (by as much as 40 percent), while skeletal muscle protein drops much more slowly. During this situation, protein breakdown becomes a source of indispensable amino acid needs for synthesis of proteins critical to maintaining essential body function. This labile protein reserve in humans is unlikely to account for more than about 1 percent of total body protein. Thus, the immediately accessible stores of protein (which serve as the source of indispensable amino acids and amino nitrogen) cannot be considered in the same light as the huge energy stores in the form of body fat; the labile protein reserve is similar in weight to the glycogen store. /Amino acids/ For more Bionecessity (Complete) data for (L)-Phenylalanine (19 total), please visit the HSDB record page. Absorbed from the small intestine by a sodium dependent active transport process. ... It diffuses across placental membrane reaching higher fetal than maternal levels. In rhesus monkey when serum maternal levels are 1-2 mg/100 mL near full term there is an approx 1.5:1 diffusion rate, but when maternal levels ... high (25 mg/100 mL) fetal serum ... reach 45 mg/100 mL to detriment of fetus. /Phenylalanine/ Although the free amino acids dissolved in the body fluids are only a very small proportion of the body's total mass of amino acids, they are very important for the nutritional and metabolic control of the body's proteins. ... Although the plasma compartment is most easily sampled, the concentration of most amino acids is higher in tissue intracellular pools. Typically, large neutral amino acids, such as leucine and phenylalanine, are essentially in equilibrium with the plasma. Others, notably glutamine, glutamic acid, and glycine, are 10- to 50-fold more concentrated in the intracellular pool. Dietary variations or pathological conditions can result in substantial changes in the concentrations of the individual free amino acids in both the plasma and tissue pools. Table: Comparison of the Pool Sizes of Free and Protein-Bound Amino Acids in Rat Muscle [Table#3668] After ingestion, proteins are denatured by the acid in the stomach, where they are also cleaved into smaller peptides by the enzyme pepsin, which is activated by the increase in stomach acidity that occurs on feeding. The proteins and peptides then pass into the small intestine, where the peptide bonds are hydrolyzed by a variety of enzymes. These bondspecific enzymes originate in the pancreas and include trypsin, chymotrypsins, elastase, and carboxypeptidases. The resultant mixture of free amino acids and small peptides is then transported into the mucosal cells by a number of carrier systems for specific amino acids and for di- and tri-peptides, each specific for a limited range of peptide substrates. After intracellular hydrolysis of the absorbed peptides, the free amino acids are then secreted into the portal blood by other specific carrier systems in the mucosal cell or are further metabolized within the cell itself. Absorbed amino acids pass into the liver, where a portion of the amino acids are taken up and used; the remainder pass through into the systemic circulation and are utilized by the peripheral tissues. /Amino acids/ For more Absorption, Distribution and Excretion (Complete) data for (L)-Phenylalanine (13 total), please visit the HSDB record page. Hepatic. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver. Pathways of amino acid metabolism- L-phenylalanine; product of oxidative deamination or transamination: phenylpyruvic acid. Product of decarboxylation: phenylethylamine. Phenylalanine to tyrosine. L-Phenylalanine yields in man: N-acetyl-L-phenylalanine; benzoic acid; probably in man, 2,5-dihydroxy-L-phenylalanine. /From table/ L-Phenylalanine yields in man: phenethylamine; phenylpyruvic acid; L-tyrosine. /From table/ L-Phenylalanine yields L-m-tyrosine in rat. /From table/ For more Metabolism/Metabolites (Complete) data for (L)-Phenylalanine (12 total), please visit the HSDB record page. Hepatic. L-phenylalanine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body, where it undergoes metabolic reactions similar to those that take place in the liver. The supposed antidepressant effects of L-phenylalanine may be due to its role as a precursor in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects. The mechanism of L-phenylalanine's possible antivitiligo activity is not well understood. It is thought that L-phenylalanine may stimulate the production of melanin in the affected skin Amino acids are selected for protein synthesis by binding with transfer RNA (tRNA) in the cell cytoplasm. The information on the amino acid sequence of each individual protein is contained in the sequence of nucleotides in the messenger RNA (mRNA) molecules, which are synthesized in the nucleus from regions of DNA by the process of transcription. The mRNA molecules then interact with various tRNA molecules attached to specific amino acids in the cytoplasm to synthesize the specific protein by linking together individual amino acids; this process, known as translation, is regulated by amino acids (e.g., leucine), and hormones. Which specific proteins are expressed in any particular cell and the relative rates at which the different cellular proteins are synthesized, are determined by the relative abundances of the different mRNAs and the availability of specific tRNA-amino acid combinations, and hence by the rate of transcription and the stability of the messages. From a nutritional and metabolic point of view, it is important to recognize that protein synthesis is a continuing process that takes place in most cells of the body. In a steady state, when neither net growth nor protein loss is occurring, protein synthesis is balanced by an equal amount of protein degradation. The major consequence of inadequate protein intakes, or diets low or lacking in specific indispensable amino acids relative to other amino acids (often termed limiting amino acids), is a shift in this balance so that rates of synthesis of some body proteins decrease while protein degradation continues, thus providing an endogenous source of those amino acids most in need. /Amino acids/ The mechanism of intracellular protein degradation, by which protein is hydrolyzed to free amino acids, is more complex and is not as well characterized at the mechanistic level as that of synthesis. A wide variety of different enzymes that are capable of splitting peptide bonds are present in cells. However, the bulk of cellular proteolysis seems to be shared between two multienzyme systems: the lysosomal and proteasomal systems. The lysosome is a membrane-enclosed vesicle inside the cell that contains a variety of proteolytic enzymes and operates mostly at acid pH. Volumes of the cytoplasm are engulfed (autophagy) and are then subjected to the action of the protease enzymes at high concentration. This system is thought to be relatively unselective in most cases, although it can also degrade specific intracellular proteins. The system is highly regulated by hormones such as insulin and glucocorticoids, and by amino acids. The second system is the ATP-dependent ubiquitin-proteasome system, which is present in the cytoplasm. The first step is to join molecules of ubiquitin, a basic 76-amino acid peptide, to lysine residues in the target protein. Several enzymes are involved in this process, which selectively targets proteins for degradation by a second component, the proteasome. /Amino acids/
| 50
| 2.2
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C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/6140.sdf
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D00022
|
Tyrosine
|
C9H11NO3
| 6,057
| 181.19
| -2.3
| 83.6
| 176
| 3
| 4
|
C1=CC(=CC=C1CC(C(=O)O)N)O
|
L-tyrosine is an optically active form of tyrosine having L-configuration. It has a role as an EC 1.3.1.43 (arogenate dehydrogenase) inhibitor, a nutraceutical, a micronutrient and a fundamental metabolite. It is an erythrose 4-phosphate/phosphoenolpyruvate family amino acid, a proteinogenic amino acid, a tyrosine and a L-alpha-amino acid. It is functionally related to a L-tyrosinal. It is a conjugate base of a L-tyrosinium. It is a conjugate acid of a L-tyrosinate(1-). It is an enantiomer of a D-tyrosine. It is a tautomer of a L-tyrosine zwitterion.
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Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine. This relationship is much like that between cysteine and methionine. Half of the phenylalanine required goes into the production of tyrosine; if the diet is rich in tyrosine itself, the requirements for phenylalanine are reduced by about 50%. The mechanism of L-tyrosine's antidepressant activity can be accounted for by the precursor role of L-tyrosine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
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Tyrosine is claimed to act as an effective antidepressant, however results are mixed. Tyrosine has also been claimed to reduce stress and combat narcolepsy and chronic fatigue, however these claims have been refuted by some studies.
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Tyrosine is a nonessential amino acid synthesized in the body from phenylalanine. Tyrosine is critical for the production of the body's proteins, enzymes and muscle tissue. Tyrosine is a precursor to the neurotransmitters norepinephrine and dopamine. It can act as a mood elevator and an anti-depressant. It may improve memory and increase mental alertness. Tyrosine aids in the production of melanin and plays a critical role in the production of thyroxin (thyroid hormones). Tyrosine deficiencies are manifested by hypothyroidism, low blood pressure and low body temperature. Supplemental tyrosine has been used to reduce stress and combat narcolepsy and chronic fatigue. Experiments were conducted with immature Beagle dogs to determine the dietary requirement for phenylalanine. With purified L-amino acid diets the requirement for this aromatic amino acid to optimize growth, feed efficiency and nitrogen balance was found to be 0.8%. Dietary limitations in the quantity of phenylalanine resulted in an increase in plasma and urinary urea. Breakpoint analysis of plasma phenylalanine concentrations also indicated a dietary requirement of 0.8%. The present data indicate that the dietary requirement for phenylalanine can be met by supplying approximately 195 mg per 100 kcal metabolizable energy or 518 mg/kg body weight per day. In a separate study, tyrosine was found to meet approximately 46% of the phenylalanine requirement of the immature dog. Consumption of diets containing tyrosine in the presence of optimal phenylalanine did not further stimulate growth, feed efficiency or nitrogen balance. L-tyrosine is absorbed from the small intestine by a sodium-dependent active transport process. Semi-chronic exposure of ICR male Mice to Aflatoxin B1 in non-toxic doses results in elevated lung tryptophan levels without change in serotonin or 5-hydroxyindole-3-acetic acid levels. This change is organ specific in that tryptophan levels are not altered in spleen, duodenum, heart or central nervous system. Acute (48 hr) flunixin treatment decreases lung tryptophan levels and reverses the Aflatoxin B1 mediated increase in lung tryptophan levels. On the other hand, flunixin treatment decreases central nervous system tryptophan levels in control mice but not in Aflatoxin B1 treated mice. Aflatoxin B1 treated mice have an increase in splenic serotonin content. Acute (48 hr) treatment of mice with E. coli lipopolysaccharide also increases splenic serotonin, and Aflatoxin B1 treatment followed by lipopolysaccharide have a slightly additive effect on spleen serotonin content. Treatment of mice with lipopolysaccharide increases heart serotonin, an effect which is not altered in Aflatoxin B1 pretreated mice. Both lipopolysaccharide and Aflatoxin B1 per se increases lung tyrosine levels although the combination of treatments is not significantly different from the control value. Flunixin treatment increases lung tyrosine levels, an effect which is not altered by Aflatoxin B1 pretreatment. Acute treatment with either lipopolysaccharide or flunixin decreases the central nervous system tryptophan/tyrosine ratio; pretreatment with Aflatoxin B1 prevents those changes in the central nervous system tryptophan/tyrosine ratio. Central nervous system catecholamines are reduced in Aflatoxin B1 pretreated mice. However, central nervous system catecholamine changes in Aflatoxin B1 treated mice are normalized by vitamin E supplementation during the treatment period. Male Wistar rats were divided in free choice conditions into heavy-drinkers consuming greater than 3.5 g/kg of ethanol daily, and light-drinkers consuming less than 2.0 g/kg/day. Subsequent 30 day intragastric administration of 25% ethanol (8-11 g/kg/day) caused an increase in permeability of the blood brain barrier to 14(C)-tyrosine, 14(C)-tryptophan and 14(C)-DOPA at all the stages of alcoholization. All the changes were more pronounced in light-drinkers than in heavy- drinker rats. Disulfiram, and to a lesser extent phenazepam and diazepam, when repeatedly injected (for 16-30 days) together with ethanol aggravated its effects. Effects of mercury chloride (100 uM) para-chloromercuribenzene sulfonate (1 uM), and oxophenylarsine (250 uM) were determined on (a) the rate of sodium pump activity in intact winter flounder intestine; (b) activity of sodium potassium ATPase in tissue homogenates; and (c) sodium-dependent and sodium independent uptake of tyrosine in brush border membrane vesicles. All three agents decreased cell potassium, although effects on cell potassium lagged behind those for inhibition of the ATPase. At the concentrations used in the Ussing chamber (or at one-tenth concentration), all agents completely inhibited sodium potassium ATPase activity in enzyme assays performed with tissue homogenates. In contrast, only mercury chloride decreased sodium dependent uptake of tyrosine by brush border membrane vesicles. These results suggest that mercurial and arsenical effects on tyrosine absorption are due to inhibition of the sodium potassium ATPase thus decreasing the driving force for the cellular uptake by the sodium tyrosine cotransport system. Direct effects on sodium tyrosine cotransport may play a role in the inhibition observed with mercury chloride, but not for para-chloromercuribenzene sulfonate or oxophenylarsine. Female Sprague-Dawley rats were treated acutely (12-hr) with aflatoxin B1 (100 ug/kg ip) or vehicle (10% acetone in 0.9% sodium chloride) and regional brain levels of tryptophan, serotonin and tyrosine were assayed. Brainstem but not cerebellar or cortical tyrosine levels were decreased in aflatoxin B1-treated rats. Brain tryptophan was increased in all 3 brain regions by acute aflatoxin B1 treatment, while serotonin levels were unaltered in the cerebellum and cortex and decreased in the brainstem. These experiments indicate that acute aflatoxin B1 treatment differentially alters brain amino acids and serotonin and that changes in brain tryptophan, the serotonin precursor, do not parallel changes in brain serotonin. For more Absorption, Distribution and Excretion (Complete) data for L-TYROSINE (10 total), please visit the HSDB record page. In the liver, L-tyrosine is involved in a number of biochemical reactions, including protein synthesis and oxidative catabolic reactions. L-tyrosine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body. /METABOLIC PATHWAY FOR L-TYROSINE:/ /TYROSINE GIVES/ P-HYDROXYPHENYLPYRUVIC ACID GIVES CO2 + HOMOGENTISIC ACID GIVES MALEYLACETOACETIC ACID GIVES FUMARYLACETOACETIC ACID GIVES FUMARATE + ACETOACETATE; TYROSINE GIVES 3,4-DIHYDROXYPHENYLALANINE GIVES CO2 + 3,4-DIHYDROXYPHENYLETHYLAMINE GIVES NORADRENALIN GIVES ADRENALIN. L-TYROSINE GIVES N-ACETYL-L-TYROSINE IN MAN; GIVES 3-CARBOXY-L-TYROSINE IN RESEDA; GIVES P-COUMARIC ACID IN SUGAR CANE, L-TYROSINE GIVES PARA-CRESOL IN PROTEUS; GIVES 3,4-DIHYDROXY-L-PHENYLALANINE IN HAMSTER; GIVES 3,4-DIHYDROXYSTILBENE-2-CARBOXYLIC ACID IN HYDRANGEA, L-TYROSINE GIVES 2,7-DIMETHYLNAPHTHOQUINONE IN CHIMAPHILA; GIVES L-DITYROSINE IN BEEF; GIVES PARA-HYDROXYMANDELONITRILE IN SORGHUM, L-TYROSINE GIVES PARA-HYDROXYPHENYLACETALDOXIME IN AUBRETIA; GIVES PARA-HYDROXYPHENYLPYRUVIC ACID IN RAT; GIVES 3-IODO-L-TYROSINE IN BEEF; L-TYROSINE GIVES LACHNANTHOSIDE IN LACHNANTHES; LOPHOCERINE IN LOPHOCERUS; MESEMBRINE IN SCELETIUM; NARWEDINE IN DAFFODIL, L-TYROSINE GIVES NOVOBIOCIN IN STREPTOMYCES; PHENOL IN RAT; BETA-TOCOPHEROL IN ANABAENA; TYLOPHORINE IN TYLOPHORA, L-TYROSINE GIVES TYRAMINE IN RAT; GIVES BETA-TYROSINE IN BACILLUS; GIVES L-TYROSINE HYDROXAMATE IN BEEF. L-TYROSINE GIVES L-TYROSINE-4-PHOSPHATE IN FLY; GIVES XANTHOCILLIN IN PENICILLIUM. /FROM TABLE/ Metabolism of tyrosine was impaired after chronic alcoholization of rats with 10% ethanol within 10 months. Within the first 3-4 months activation of tyrosine aminotransferase and a decrease in phenylalanine hydroxylase activity were found in liver tissue. Activity of tyrosine aminotransferase was not increased during the long term alcohol intoxication. At the same time, activity of tyrosine aminotransferase was decreased within 5-6 months simultaneously with activation of phenylalanine hydroxylase. An increase in the alcohol dehydrogenase activity was also observed in rat liver tissue during the initial period of intoxication. The enzymatic activity was decreased beginning from the 3-4 months of the alcoholization and maintained at the low level. Hyperthermia augmented these alterations observed in chronic alcoholization of rats. Spontaneous behavior subsequent to acute oral administration of high doses of aspartame, phenylalanine, or tyrosine was analyzed using a computer pattern recognition system. Spraque Dawley male rats (250-300 g) were dosed orally with aspartame (500 or 100 mg/kg), phenylalanine (281 or 562 mg/kg), or tyrosine (309 or 618 mg/kg), and their behavior was analyzed 1 hr after dosing. The computer pattern recognition system recorded and classifed 13 different behavioral acts performed by the animals during the first 15-min exploration of a novel environment. These doses of aspartame, phenylalanine, and tyrosine did not induce any significant changes in spontaneous behavior. Unlike low doses of amphetamine and despite high plasma concentrations of phenylalanine and tyrosine, no behavioral alteration was detected by the computer pattern recognition system. For more Metabolism/Metabolites (Complete) data for L-TYROSINE (7 total), please visit the HSDB record page. In the liver, L-tyrosine is involved in a number of biochemical reactions, including protein synthesis and oxidative catabolic reactions. L-tyrosine that is not metabolized in the liver is distributed via the systemic circulation to the various tissues of the body. Tyrosine is produced in cells by hydroxylating the essential amino acid phenylalanine. This relationship is much like that between cysteine and methionine. Half of the phenylalanine required goes into the production of tyrosine; if the diet is rich in tyrosine itself, the requirements for phenylalanine are reduced by about 50%. The mechanism of L-tyrosine's antidepressant activity can be accounted for by the precursor role of L-tyrosine in the synthesis of the neurotransmitters norepinephrine and dopamine. Elevated brain norepinephrine and dopamine levels are thought to be associated with antidepressant effects.
| 0.453
| 2.06
|
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/6057.sdf
|
D00023
|
Urea
|
CH4N2O
| 1,176
| 60.056
| -1.4
| 69.1
| 29
| 2
| 1
|
C(=O)(N)N
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Urea appears as solid odorless white crystals or pellets. Density 1.335 g /cc. Noncombustible.
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Urea
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Urea is used topically for debridement and promotion of normal healing of hyperkeratotic surface lesions, particularly where healing is retarded by local infection, necrotic tissue, fibrinous or purulent debris or eschar. Urea is useful for the treatment of hyperkeratotic conditions such as dry, rough skin, dermatitis, psoriasis, xerosis, ichthyosis, eczema, keratosis, keratoderma, corns and calluses, as well as damaged, devitalized and ingrown nails.
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Urea is a keratolytic emollient that works to treat or prevent dry, rough, scaly, itchy skin. B - Blood and blood forming organs D - Dermatologicals D02AE01 SOME SMALL, WATER SOL, BUT NONIONIZABLE COMPD SUCH AS UREA READILY TRAVERSE MAMMALIAN MEMBRANES, PROBABLY ALONG WITH WATER, BY WAY OF THE PORES. THIS FILTRATION PROCESS IS PARTICULARLY RAPID BETWEEN CAPILLARIES & EXTRACELLULAR FLUID. ... UREA ... PENETRATES OTHER CELLS RAPIDLY, ENTERS THE BRAIN ONLY VERY SLOWLY ... ... DISTRIBUTED APPROX IN TOTAL BODY WATER ... HAVE BEEN USED FOR MEASUREMENT OF TOTAL BODY WATER. EXCRETION OF UREA DURING SWEATING IN MAN: 1.84 SWEAT/PLASMA RATIO WITH PKA @ 13.8. /FROM TABLE/ For more Absorption, Distribution and Excretion (Complete) data for UREA (6 total), please visit the HSDB record page. ... The primary mechanism of ammonia toxicosis appears to be inhibition of the citric acid cycle. There is an increase in anaerobic glycolysis, blood glucose, and blood lactate ... . Acidosis is manifested. The exact means by which ammonia blocks the citric acid cycle is not known. It is postulated that ammonia saturation of the glutamine-synthesizing system causes a backing-up in the citrate cycle, a decrease in its intermediates, and a decrease in energy production and cellular respiration, which leads to convulsions ... . The decrease of citrate cycle intermediates is postulated to result from reamination of pyruvic, ketoglutaric, and oxaloacetic acids.
| null | 0.1
|
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/1176.sdf
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D00025
|
Sucrose
|
C12H22O11
| 5,988
| 342.3
| -3.7
| 190
| 395
| 8
| 11
|
C(C1C(C(C(C(O1)OC2(C(C(C(O2)CO)O)O)CO)O)O)O)O
|
Sucrose appears as white odorless crystalline or powdery solid. Denser than water.
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A4: Not classifiable as a human carcinogen.
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No drug information available
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Substances that sweeten food, beverages, medications, etc., such as sugar, saccharine or other low-calorie synthetic products. (From Random House Unabridged Dictionary, 2d ed) (See all compounds classified as Sweetening Agents.)
| 100
| 12.6
|
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5988.sdf
|
D00026
|
L-Cysteine
|
C3H7NO2S
| 5,862
| 121.16
| -2.5
| 64.3
| 75
| 3
| 4
|
C(C(C(=O)O)N)S
|
L-cysteine is an optically active form of cysteine having L-configuration. It has a role as a flour treatment agent, a human metabolite and an EC 4.3.1.3 (histidine ammonia-lyase) inhibitor. It is a serine family amino acid, a proteinogenic amino acid, a cysteine and a L-alpha-amino acid. It is a conjugate base of a L-cysteinium. It is a conjugate acid of a L-cysteinate(1-). It is an enantiomer of a D-cysteine. It is a tautomer of a L-cysteine zwitterion.
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IDENTIFICATION AND USE: Cysteine forms white or colorless crystals. It is used in biochemical and nutrition research, as a reducing agent in bread doughs (up to 90 ppm). It is also used as flavor enhancer and medication, including veterinary medication. HUMAN EXPOSURE AND TOXICITY: Cysteine solution (3%) was not irritating for human eyes. ANIMAL STUDIES: A single ocular application of L-cysteine to rabbits at a dose of 0.1 g produced slight irritant effects, which were fully reversible within 48 hours. The single dermal application of L-cysteine to three rabbits at a dose of 0.5 g showed neither irritant nor corrosive effects. Decreased litter size observed in rats receiving high-dose cysteine, which was related to the degeneration and/or death of ovulated unfertilized oocytes and embryos with changes in the zona pellucida, which was already affected in the ovary. Pregnant mice and rats were treated s.c. with 1.2 mg per g on the last day of pregnancy and brain degeneration was observed one day later in the fetus. L-Cysteine is considered to be non-mutagenic in the HPRT locus using V79 cells of the Chinese Hamster. L-Cysteine did not induce structural chromosomal aberrations in the V79 Chinese hamster cell line. ECOTOXICITY STUDIES: The objective of the study was to determine the effects of cysteine on postthaw sperm motility, duration of sperm motility, DNA damage, and fertility in the common carp (Cyprinus carpio). Supplementation with cysteine increased the fertilization and hatching rate and decreased DNA damage.
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For the prevention of liver damage and kidney damage associated with overdoses of acetaminophen
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Due to this ability to undergo redox reactions, cysteine has antioxidant properties. Cysteine is an important source of sulfur in human metabolism, and although it is classified as a non-essential amino acid, cysteine may be essential for infants, the elderly, and individuals with certain metabolic disease or who suffer from malabsorption syndromes. Cysteine may at some point be recognized as an essential or conditionally essential amino acid. L-Cysteine is the central compound in sulfur metabolism in the human body. In proteins the formation of disulfide bonds between the thiol groups of cysteine plays an important role for tertiary structure and enzymatic activity ... . Amino acid catabolism is essential for adjusting pool sizes of free amino acids and takes part in energy production as well as nutrient remobilization. The carbon skeletons are generally converted to precursors or intermediates of the tricarboxylic acid cycle. In the case of cysteine, the reduced sulfur derived from the thiol group also has to be oxidized in order to prevent accumulation to toxic concentrations. ... L-Cysteine is the central compound in sulfur metabolism in the human body. In proteins the formation of disulfide bonds between the thiol groups of cysteine plays an important role for tertiary structure and enzymatic activity; cysteine is however always incorporated in the polypeptide chain as cysteine. L-Cysteine is degraded to pyruvate in two steps: one is removal of sulfur and the other is a transamination. Cysteine can be metabolized to form taurine and carbon dioxide through the cysteinsulfinate pathway, where the initial step is oxidation of cysteine to cysteine sulfinate. This step is catalyzed by cysteine dioxygenase. Cysteine sulfinate may then be decarboxylated to form taurine or it may be metabolized via the putative intermediate beta-sulfinylpyruvate to pyruvate and sulfite and then to carbon dioxide and sulfate. Amino acid catabolism is essential for adjusting pool sizes of free amino acids and takes part in energy production as well as nutrient remobilization. The carbon skeletons are generally converted to precursors or intermediates of the tricarboxylic acid cycle. In the case of cysteine, the reduced sulfur derived from the thiol group also has to be oxidized in order to prevent accumulation to toxic concentrations. Here we present a mitochondrial sulfur catabolic pathway catalyzing the complete oxidation of L-cysteine to pyruvate and thiosulfate. After transamination to 3-mercaptopyruvate the sulfhydryl group from L-cysteine is transferred to glutathione by sulfurtransferase 1 and oxidized to sulfite by the sulfur dioxygenase ETHE1. Sulfite is then converted to thiosulfate by addition of a second persulfide group by sulfurtransferase 1. This pathway is most relevant during early embryo development and for vegetative growth under light limiting conditions. Characterization of a double mutant produced from Arabidopsis thaliana T-DNA insertion lines for ETHE1 and sulfurtransferase 1 revealed that an intermediate of the ETHE1 dependent pathway, most likely a persulfide, interferes with amino acid catabolism and induces early senescence. Uremic toxins tend to accumulate in the blood either through dietary excess or through poor filtration by the kidneys. Most uremic toxins are metabolic waste products and are normally excreted in the urine or feces. Cysteine can usually be synthesized by the human body under normal physiological conditions if a sufficient quantity of methionine is available. Cysteine is typically synthesized in the human body when there is sufficient methionine available. Cysteine exhibits antioxidant properties and participates in redox reactions. Cysteine's antioxidant properties are typically expressed in the tripeptide glutathione, which occurs in humans as well as other organisms. Glutathione (GSH) typically requires biosynthesis from its constituent amino acids, cysteine, glycine, and glutamic acid, due to its limited systemic availability. Glutamic acid and glycine are readily available in the diets of most industrialized countries, but the availability of cysteine can be the limiting substrate. In human metabolism, cysteine is also involved in the generation of sulfide present in iron-sulfur clusters and nitrogenase by acting as a precursor. In a 1994 report released by five top cigarette companies, cysteine is one of the 599 additives to cigarettes. Its use or purpose, however, is unknown, like most cigarette additives. Its inclusion in cigarettes could offer two benefits: Acting as an expectorant, since smoking increases mucus production in the lungs; and increasing the beneficial antioxidant glutathione (which is diminished in smokers).
| null | 1.71
|
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/5862.sdf
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D00027
|
Uracil
|
C4H4N2O2
| 1,174
| 112.09
| -1.1
| 58.2
| 161
| 2
| 2
|
C1=CNC(=O)NC1=O
|
Uracil is a common and naturally occurring pyrimidine nucleobase in which the pyrimidine ring is substituted with two oxo groups at positions 2 and 4. Found in RNA, it base pairs with adenine and replaces thymine during DNA transcription. It has a role as a prodrug, a human metabolite, a Daphnia magna metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite, a mouse metabolite and an allergen. It is a pyrimidine nucleobase and a pyrimidone. It is a tautomer of a (4S)-4-hydroxy-3,4-dihydropyrimidin-2(1H)-one.
| null |
No drug information available
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No pharmacodynamics information available
| 3.6
| 9.45
|
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/1174.sdf
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D00028
|
Glycerin
|
C3H8O3
| 753
| 92.09
| -1.8
| 60.7
| 25
| 3
| 3
|
C(C(CO)O)O
|
Glycerine appears as a colorless to brown colored liquid. Combustible but may require some effort to ignite.
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No indication of carcinogenicity to humans (not listed by IARC).
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It is used as a solvent, emollient, pharmaceutical agent, and sweetening agent.
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Glycerin is commonly classified as an osmotic laxative but may act additionally or alternatively through its local irritant effects; it may also have lubricating and fecal softening actions. Glycerin suppositories usually work within 15 to 30 minutes. Liquids that dissolve other substances (solutes), generally solids, without any change in chemical composition, as, water containing sugar. (Grant and Hackh's Chemical Dictionary, 5th ed) (See all compounds classified as Solvents.) Substances that provide protection against the harmful effects of freezing temperatures. (See all compounds classified as Cryoprotective Agents.) PDC6A3C0OX GLYCERIN Established Pharmacologic Class [EPC] - Non-Standardized Chemical Allergen Physiologic Effects [PE] - Increased Histamine Release Physiologic Effects [PE] - Cell-mediated Immunity Physiologic Effects [PE] - Increased IgG Production Chemical Structure [CS] - Allergens Chemical Structure [CS] - Glycerol Glycerin is a Non-Standardized Chemical Allergen. The physiologic effect of glycerin is by means of Increased Histamine Release, and Cell-mediated Immunity, and Increased IgG Production. GLYCERIN Glycerol [CS]; Allergens [CS]; Non-Standardized Chemical Allergen [EPC]; Increased IgG Production [PE]; Cell-mediated Immunity [PE]; Increased Histamine Release [PE] GLYCERIN SUPPOSITORY Non-Standardized Chemical Allergen [EPC]; Increased IgG Production [PE]; Glycerol [CS]; Allergens [CS]; Increased Histamine Release [PE]; Cell-mediated Immunity [PE] GLYCERINE Increased Histamine Release [PE]; Cell-mediated Immunity [PE]; Non-Standardized Chemical Allergen [EPC]; Increased IgG Production [PE]; Glycerol [CS]; Allergens [CS] GLYCERINUM Glycerol [CS]; Allergens [CS]; Non-Standardized Chemical Allergen [EPC]; Increased IgG Production [PE]; Cell-mediated Immunity [PE]; Increased Histamine Release [PE] REGENER-EYES Cell-mediated Immunity [PE]; Increased Histamine Release [PE]; Allergens [CS]; Glycerol [CS]; Increased IgG Production [PE]; Non-Standardized Chemical Allergen [EPC] VITAMIN C SERUM Cell-mediated Immunity [PE]; Increased Histamine Release [PE]; Allergens [CS]; Glycerol [CS]; Increased IgG Production [PE]; Non-Standardized Chemical Allergen [EPC] GLYCEROL-SALINE DILUENT Allergens [CS]; Glycerol [CS]; Increased IgG Production [PE]; Non-Standardized Chemical Allergen [EPC]; Cell-mediated Immunity [PE]; Increased Histamine Release [PE] A - Alimentary tract and metabolism A - Alimentary tract and metabolism Well absorbed orally, poorly absorbed rectally. Studies in humans and animals indicate glycerol is rapidly absorbed in the intestine and the stomach Approx 7-14% of dose is excreted unchanged in the urine within 2.5 hr. Glycerin is distributed throughout the blood. Although glycerin generally does not appear in ocular fluids, it may enter the orbital sac when the eye is inflamed, with a consequent decrease in osmotic effect. Data from studies in humans and animals indicate glycerol is rapidly absorbed in the intestine and the stomach, distributed over the extracellular space and excreted. After hydrolysis of glycerol esters in the intestine, glycerol is readily absorbed. Following rectal administration, glycerin and sorbitol are poorly absorbed; colonic evacuation of glycerin rectal suppositories or enemas occurs within 15-60 minutes, while colonic evacuation of oral sorbitol occurs within 24-48 hours. Following absorbption from GI tract, glycerin is distributed throughout the blood. Although glycerin glycerin generally does not appear in ocular fluids, it may enter the orbital sac when the eye is inflamed, with a consequent decrease in osmotic effect. For more Absorption, Distribution and Excretion (Complete) data for GLYCERIN (7 total), please visit the HSDB record page. Glycerin is a substrate for synthesis of triacylglycerols and of phospholipids in the liver and adipose tissue. When fat metabolized as a source of energy, glycerol and fatty acids are released into the bloodstream. Circulating glycerin does not glycate proteins and does not lead to the formation of advanced glycation endproducts (AGEs). In some organisms, the glycerin component can enter the glycolysis pathway directly to provide a substrate for energy or glucose production. Glycerol must be converted to their intermediate glyceraldehyde 3-phosphate before being used in glycolysis or gluconeogenesis. Glycerol metabolism is regulated by the enzymes glycerol kinase, (cytosolic) NAD+-dependent G3P dehydrogenase and (mitochondrial) FAD-linked G3P dehydrogenase. Glycerol is phosphorylated to alpha-glycerophosphate by glycerol kinase predominantly in the liver (80-90%) and kidneys (10-20%) and incorporated in the standard metabolic pathways to form glucose and glycogen. Glycerol kinase is also found in intestinal mucosa, brown adipose tissue, lymphatic tissue, lung and pancreas. Glycerol may also be combined with free fatty acids in the liver to form triglycerides (lipogenesis) which are distributed to the adipose tissues. The turnover rate is directly proportional to plasma glycerol levels. Glycerol is endogenous in the human body. It enters the glycolytic pathway after its conversion in the liver to glycerol-3-phosphate by glycerol kinase. Glycerol-3-phosphate is then oxidized by glycerol-3-phosphate dehydrogenase to yield dihydroxyacetone phosphate, which is then isomerized to glyceral-dehyde-3-phosphate, eventually yielding pyruvic acid. Glycerol esters are hydrolyzed to glycerol and the corresponding carboxylic acids. The hydrolysis is catalysed by intestinal lipase, which attacks the ester bonds at carbons 1 and 3. The ester bond at carbon 2 is more resistant to hydrolysis, possibly because of its stereochemistry and steric hindrance. The beta-monoglyceride can, however, spontaneously isomerise to the alpha-form (3-acylglycerol), permitting further hydrolysis to yield glycerol. Glycerol, pyruvic acid, and lactic acid are endogenous in humans. Glycerol and pyruvic acid are metabolized completely and are not excreted. ... Glycerol is metabolized via the glycolytic pathway after it has been converted in the liver to glycerol-3-phosphate. For more Metabolism/Metabolites (Complete) data for GLYCERIN (6 total), please visit the HSDB record page. 30 - 45 minutes Elimination half-life of glycerin is about 30-40 min. When administered rectally, glycerin exerts a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexively stimulating evacuation. Glycerin decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. Glycerin (glycerol) and sorbitol are hyperosmotic laxatives. When administered rectally, glycerin and sorbitol exert a hygroscopic and/or local irritant action, drawing water from the tissues into the feces and reflexly stimulating evacuation. The extent to which the simple physical distention of the rectum and the hygroscopic and/or local irritant actions are responsible for the laxative effects of some of these drugs is not known. Only extremely high oral doses of sorbitol (25 g daily) or glycerin exert laxative action. /Glycerin/ decreases intraocular pressure by creating an osmotic gradient between the blood and intraocular fluid, causing fluid to move out of the aqueous and vitreous humors into the bloodstream. The physicochemical effects of a series of alkanols, alkanediols and glycerol on erythrocyte shape and hemolysis at 4 and 20 degrees C were examined. We calculated the dielectric constant of the incubation medium, Ds, and the dielectric constant of the erythrocyte membrane Dm in the presence of organic solutes. The ratio Ds/Dm = -38.48 at 20 degrees C defines the normal biconcave shape in a medium without hemolytic agents. A decrease in Ds/Dm favors externalization or internalization with consequent hemolysis. Alkanols and alkanediols convert biconcave erythrocytes into echinocytes, which is accompanied by an increase in the projected surface area. Glycerol converts biconcave erythrocytes into stomatocytes, which was accompanied by a marginal decrease in the projected surface area. Progressive externalization in alkanols and alkanediols or internalization in glycerol resulted in a decrease in the projected surface area and the formation of smooth spheres. The degree of shape change induced was related to the degree of hemolysis and the ratio Ds/Dm. A decrease in temperature reduced both the degree of shape change and hemolysis. .../Thus/ physicochemical toxicity may be a result of a temperature dependent hydrophobic interaction between the organic solutes and the membrane and is best interpreted by the ability of the solutes to change Ds and Dm.
| 100
| 14.4
|
C:/Users/user/Desktop/Sem 9/DDP/Dataset_creation/SampleData/753.sdf
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D00029
|
Biotin
|
C10H16N2O3S
| 171,548
| 244.31
| 0.3
| 104
| 298
| 3
| 4
|
C1C2C(C(S1)CCCCC(=O)O)NC(=O)N2
|
Biotin is an organic heterobicyclic compound that consists of 2-oxohexahydro-1H-thieno[3,4-d]imidazole having a valeric acid substituent attached to the tetrahydrothiophene ring. The parent of the class of biotins. It has a role as a prosthetic group, a coenzyme, a nutraceutical, a human metabolite, a Saccharomyces cerevisiae metabolite, an Escherichia coli metabolite, a mouse metabolite, a cofactor and a fundamental metabolite. It is a member of biotins and a vitamin B7. It is a conjugate acid of a biotinate.
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Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids.
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For nutritional supplementation, also for treating dietary shortage or imbalance. Treatment of multiple sclerosis
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Biotin is a water-soluble B-complex vitamin which is composed of an ureido ring fused with a tetrahydrothiophene ring, which attaches a valeric acid substituent at one of its carbon atoms. Biotin is used in cell growth, the production of fatty acids, metabolism of fats, and amino acids. It plays a role in the Kreb cycle, which is the process in which energy is released from food. Biotin not only assists in various metabolic chemical conversions, but also helps with the transfer of carbon dioxide. Biotin is also helpful in maintaining a steady blood sugar level. Biotin is often recommended for strengthening hair and nails. Consequenty, it is found in many cosmetic and health products for the hair and skin. Biotin deficiency is a rare nutritional disorder caused by a deficiency of biotin. Initial symptoms of biotin deficiency include: Dry skin, Seborrheic dermatitis, Fungal infections, rashes including erythematous periorofacial macular rash, fine and brittle hair, and hair loss or total alopecia. If left untreated, neurological symptoms can develop, including mild depression, which may progress to profound lassitude and, eventually, to somnolence; changes in mental status, generalized muscular pains (myalgias), hyperesthesias and paresthesias. The treatment for biotin deficiency is to simply start taking some biotin supplements. A lack of biotin in infants will lead to a condition called seborrheic dermatitis or "cradle cap". Biotin deficiencies are extremely rare in adults but if it does occur, it will lead to anemia, depression, hair loss, high blood sugar levels, muscle pain, nausea, loss of appetite and inflamed mucous membranes. A group of water-soluble vitamins, some of which are COENZYMES. (See all compounds classified as Vitamin B Complex.) A - Alimentary tract and metabolism ... /BIOTIN/ IS ESSENTIAL IN SYNTHESIS OF FATTY ACIDS, PROTEINS, PURINES, CARBAMYLS, & DICARBOXYLIC ACID ... /IN/ POTASSIUM METAB ... /IN/ SKIN, NERVOUS SYSTEM, ADRENAL, THYROID, REPRODUCTIVE FUNCTIONS, & IN NUMEROUS VIT (B5, B6, C & FOLIC ACID) INTERRELATIONSHIPS. BIOTIN ... IS ... PRESUMED TO BE A DIETARY ESSENTIAL IN ABSENCE OF ADEQUATE MICROBIAL SYNTHESIS IN INTESTINE. Biotin deficiency may lead to dermatitis, alopecia, hypercholesterolemia, and cardiac abnormalities. Requirements may be increased and/or supplementation may be necessary in the following conditions (based on documented biotin deficiency): Biotinidase deficiency, gastrectomy, or seborrheic dermatitis of infancy For more Bionecessity (Complete) data for BIOTIN (31 total), please visit the HSDB record page. Systemic - approximately 50% The intestine is exposed to biotin from a few sources: the diet, biotin supplements and biotin synthesized by bacteria in the large intestine. Dietary biotin exists in free and protein-bound forms. Protein-bound biotin is digested by proteases and peptidases to biotin-containing oligopeptides and biocytin (epsilon-N-biotinyl-L-lysine). Biocytin and the biotin-containing oligopeptides are converted to biotin via the enzyme biotinidase. Biotin - both dietary-derived biotin and supplementary biotin - is efficiently absorbed from the small intestine. At doses of biotin derived from food, biotin appears to be transported into enterocytes by a sodium -dependent carrier. At higher doses of biotin,absorption appears to occur by passive diffusion. Absorption of the biotin produced by the colonic microflora, appears to occur by a carrier mediated process in the proximal large intestine. Elimination: Primarily in urine. Protein binding: Primarily to plasma proteins. Absorption: approximately 50%. For more Absorption, Distribution and Excretion (Complete) data for BIOTIN (32 total), please visit the HSDB record page. Biotin is excreted in the urine as biotin, bisnorbiotin, biotin sulfoxide, biotin sulfone, bisnorbiotin methyl ketone and tetranobiotin-1-sulfoxide. Biotin is catabolized to a number of different metabolites, including bisnorbiotin, biotin sulfoxide, biotin sulfone, bisonorbiotin methylketone and tetranorbiotin-1-sulfoxide. More than 95% of the biotin is free in the skim fraction of human milk. The concentration of biotin varies substantially in some women and exceeds that in serum by one to two order of magnitude, suggesting that there is a transport system into milk. The biotin metabolite bisnorbiotin accounts for approximately 50%. In early and transitional human milk, the biotin metabolite biotin sulfoxide accounts for about 10% of the total biotin plus metabolites. With postpartum maturation, the biotin concentration increases, but the bisnorbiotin and biotin sulfoxide concentrations still account for 25% and 8% at 5 weeks postpartum. Current studies provide no evidence for a soluble biotin-binding protein or any other mechanism that traps biotin in human milk. On a molar basis, biotin accounts for approximately half of the total avidin-binding substances in human serum and urine. Biocytin, bisnorbiotin, bisnorbiotin methylketone, biotin sulfoxide, and biotin sulfone form most of the balance. Biotin metabolism is accelerated in some individuals by anticonvulsants and during pregnancy, thereby increasing the ratio of biotin metabolites to biotin excreted in urine. An alternate fate to being incorporated into carboxylases or unchanged excretion is catabolism to an inactive metabolite before excretion in urine. About half of biotin undergoes metabolism before excretion. Two principal pathways of biotin catabolism have been identified in mammals. In the first pathway, the valeric acid side chain of biotin is degraded by beta oxidation. This leads to the formation of bisnorbiotin, tetranorbiotin, and related intermediates that are known to result from beta-oxidation of fatty acids. The cellular site of this beta-oxidation of biotin is uncertain. Nonenzymatic decarboxylation of the unstable beta-ketobiotin and beta-keto-bisnorbiotin leads to formation of bisnorbiotin methylketone and tetranorbiotin methylketone, which appear in urine. In the second pathway, the sulfur in the thiophane ring of biotin is oxidized, leading to the formation of biotin L-sulfoxide, biotin D-sulfoxide, and biotin sulfone. Combined oxidation of the ring sulfur and beta-oxidation of the side chain lead to metabolites such as bisnorbiotin sulfone. In mammals, degradation of the biotin ring to release carbon dioxide and urea is quantitatively minor. Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids. In human tissues biotin is a cofactor for the enzymatic carboxylation of four substrates: pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA. As such, it plays an important role in both carbohydrate and fat metabolism. Carbon dioxide fixation occurs in a two-step reaction, the first involving binding of carbon dioxide to the biotin moiety of the holoenzyme, and the second involving transfer of the biotin-bound carbon dioxide to an appropriate acceptor. Biotin functions in carbon dioxide fixation reactions in intermediate metabolism, transferring the carboxyl group to acceptor molecules. It acts similarly in decarboxylation reactions. Biotin is essential in human metabolism for its part in the previously described enzymatic steps, in catalyzing deamination of amino acids, and in oleic acid synthesis. Biotin is a cofactor for the enzymatic carboxylation of pyruvate, acetyl coenzyme A (CoA), propionyl CoA, and beta-methylcrotonyl CoA, and, therefore, plays an important role in carbohydrate and fat metabolism. Protein folding in the endoplasmic reticulum (ER) depends on Ca2+; uptake of Ca2+ into the ER is mediated by sarco/endoplasmic reticulum Ca2+-ATPase 3 (SERCA3). The 5'-flanking region of the SERCA3 gene (ATP2A3) contains numerous binding sites for the transcription factors Sp1 and Sp3. Biotin affects the nuclear abundance of Sp1 and Sp3, which may act as transcriptional activators or repressors. Here we determined whether biotin affects the expression of the SERCA3 gene and, thus, protein folding in human lymphoid cells. Jurkat cells were cultured in media containing 0.025 nmol/L biotin (denoted "deficient") or 10 nmol/L biotin ("supplemented"). The transcriptional activity of the full-length human SERCA3 promoter was 50% lower in biotin-supplemented cells compared to biotin-deficient cells. Biotin-dependent repressors bind to elements located 731 to 1312 bp upstream from the transcription start site in the SERCA3 gene. The following suggest that low expression of SERCA3 in biotin-supplemented cells impaired folding of secretory proteins in the ER, triggering unfolded protein response: (i) sequestration of Ca2+ in the ER decreased by 14 to 24% in response to biotin supplementation; (ii) secretion of interleukin-2 into the extracellular space decreased by 75% in response to biotin supplementation; (iii) the nuclear abundance of stress-induced transcription factors increased in response to biotin supplementation; and (iv) the abundance of stress-related proteins such ubiquitin activating enzyme 1, growth arrest and DNA damage 153 gene, X-box binding protein 1 and phosphorylated eukaryotic translation initiation factor 2alpha increased in response to biotin supplementation. Collectively, this study suggests that supplements containing pharmacological doses of biotin may cause cell stress by impairing protein folding in the ER. Evidence is emerging that biotin participates in processes other than classical carboxylation reactions. Specifically, novel roles for biotin in cell signaling, gene expression, and chromatin structure have been identified in recent years. Human cells accumulate biotin by using both the sodium-dependent multivitamin transporter and monocarboxylate transporter 1. These transporters and other biotin-binding proteins partition biotin to compartments involved in biotin signaling: cytoplasm, mitochondria, and nuclei. The activity of cell signals such as biotinyl-AMP, Sp1 and Sp3, nuclear factor (NF)-kappaB, and receptor tyrosine kinases depends on biotin supply. Consistent with a role for biotin and its catabolites in modulating these cell signals, greater than 2000 biotin-dependent genes have been identified in various human tissues. Many biotin-dependent gene products play roles in signal transduction and localize to the cell nucleus, consistent with a role for biotin in cell signaling. Posttranscriptional events related to ribosomal activity and protein folding may further contribute to effects of biotin on gene expression. Finally, research has shown that biotinidase and holocarboxylase synthetase mediate covalent binding of biotin to histones (DNA-binding proteins), affecting chromatin structure; at least seven biotinylation sites have been identified in human histones. Biotinylation of histones appears to play a role in cell proliferation, gene silencing, and the cellular response to DNA repair. Roles for biotin in cell signaling and chromatin structure are consistent with the notion that biotin has a unique significance in cell biology.
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