Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P17174 (aspartate aminotransferase)
 14,872 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

[3H]Glutamate uptake into astrocytes in primary culture was potently inhibited by the aspartate analogues L- and D-aspartic acid, DL-threo-beta-hydroxy-aspartic acid-beta-hydroxymate (IC50's: 136, 259, 168, and 560 microM, respectively) and by beta-DL-methylene-aspartate, a suicide inhibitor of aspartate aminotransferase (IC50: 524 microM), and by the endogenous sulphur-containing amino acid L-cysteinesulfinic acid (IC50: 114 microM), [3H]Glutamate uptake was not significantly affected by either N-methyl-D-aspartate or DL-homocysteine thiolactone. These results demonstrate that other excitatory amino acids including aspartate and L-cysteinesulfinic acid (but excluding L-homocysteic acid) interact with the glutamate transport system of astrocytes. Inhibition of glutamate uptake may significantly increase the level of neuronal excitability.
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PMID:Beta-DL-methylene-aspartate, an inhibitor of aspartate aminotransferase, potently inhibits L-glutamate uptake into astrocytes. 257 Oct 95

S-(2-Hydroxy-2-carboxyethyl)homocysteine, S-(3-hydroxy-3-carboxy-n-propyl)-cysteine, N-acylated S-(beta-carboxyethyl)cysteine, and N-acylated S-(3-hydroxy-3-carboxy-n-propyl) cysteine were excreted in the urine after DL-propargylglycine treatment. Cystathionine was also accumulated in several tissues of DL-propargylglycine-treated rats. N-Monoacetylcystathione was found in the liver of rats and was also detected in the kidney and serum. Cystathionine gamma-lyase activity in liver decreased to about 4% of that of control rats 24 h after the DL-propargylglycine injection, and alanine aminotransferase activity decreased to about 35% of that of control rats. On the other hand, aspartate aminotransferase and cystathionine beta-synthese activity did not show significant changes from those of control rats. The ability of normal tissues to synthesize cystathionine utilizing cystathionine beta-synthase was 1.98 +/- 0.40 mumol/min/g in liver, 0.61 +/- 0.13 in kidney, and 0.18 +/- 0.015 in brain. The maximal contents of cystathionine in rat tissues and the administered amounts of DL-propargylglycine agreed well with the ability to synthesize cystathionine in each tissue.
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PMID:Unusual metabolism of sulfur-containing amino acids in rats treated with DL-propargylglycine. 661 21

Normal serum concentrations of methionine, leucine, isoleucine and valine have been found in 10 anaesthetists using nitrous oxide under their regular working conditions without scavenging of patients' exhaled gas. Mean inhaled concentrations of nitrous oxide ranged from 150 to 400 p.p.m. The results indicate either that there was no significant inhibition of methionine synthase (attributable to oxidation of vitamin B12 by nitrous oxide) or that methionine concentrations were maintained by dietary intake or by the alternative betaine pathway of methylation of homocysteine. In either case, anaesthetists working under these conditions should not be at risk from reduced methionine concentrations. We also report normal serum activities of aspartate transaminase and gamma glutamyl transpeptidase.
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PMID:Serum methionine and hepatic enzyme activity in anaesthetists exposed to nitrous oxide. 708 22

We showed previously that supplementation for 30 d with 800 IU (727 mg) vitamin E/d did not adversely affect healthy elderly persons. We have now assessed the effects of 4 mo of supplementation with 60, 200, or 800 IU (55, 182, or 727 mg) all-rac-alpha-tocopherol/d on general health, nutrient status, liver enzyme function, thyroid hormone concentrations, creatinine concentrations, serum autoantibodies, killing of Candida albicans by neutrophils, and bleeding time in 88 healthy subjects aged >65 y participating in a double-blind, placebo-controlled trial. No side effects were reported by the subjects. Vitamin E supplementation had no effect on body weight, plasma total proteins, albumin, glucose, plasma lipids or the lipoprotein profile, total bilirubin, alkaline phosphatase, serum aspartate aminotransferase, serum alanine aminotransferase, lactate dehydrogenase, serum urea nitrogen, total red blood cells, white blood cells or white blood cell differential counts, platelet number, bleeding time, hemoglobin, hematocrit, thyroid hormones, or urinary or serum creatinine concentrations. Values from all supplemented groups were within normal ranges for older adults and were not significantly different from values in the placebo group. Vitamin E supplementation had no significant effects on plasma concentrations of other antioxidant vitamins and minerals, glutathione peroxidase, superoxide dismutase, or total homocysteine. There was no significant effect of vitamin E on serum nonspecific immunoglobulin concentrations or anti-DNA and anti-thyroglobulin antibodies. The cytotoxic ability of neutrophils against Candida albicans was not compromised. Thus, 4 mo of supplementation with 60-800 IU vitamin E/d had no adverse effects. These results are relevant for determining risk-to-benefit ratios for vitamin E supplementation.
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PMID:Assessment of the safety of supplementation with different amounts of vitamin E in healthy older adults. 970 Nov 88

Reference intervals for long-term status measures of folate, riboflavin, thiamine, and vitamin B-6 were determined in a select group of adults. Reference subjects had no adverse medical history and did not use tobacco, alcohol, or nutritional supplements, and their diets met > or =70% of the Australian recommended dietary intake for nutrients. Red blood cell concentrations of thiamine and folate were measured by microbiological methods. Vitamin B-6 and riboflavin status were measured on the basis of the erythrocyte aspartate transaminase activity coefficient and erythrocyte glutathione reductase activity coefficient, respectively. A survey of first-time blood donors, which was conducted in Australia in 1995, revealed a significant prevalence of low red blood cell thiamine concentrations (13%) when compared with the calculated normal reference intervals. However, the most important finding in the survey was that the group of healthy, nonanemic adults (first-time blood donors) was found to have a median red blood cell folate concentration 24% below the median concentration of the carefully selected (nonsupplemented) reference group. Plasma total homocysteine concentrations indicated folate deficiency in the reference group. Therefore, the 2.5th percentile cutoff for reference group red blood cell folate concentrations may have underestimated the prevalence of folate deficiency in the survey group. These data, coupled with the lack of Australian food-composition data for folate in particular, reinforce the need for monitoring nutritional status by both dietary and biochemical means. We recommend consideration of mandatory fortification of the Australian food supply with folic acid.
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PMID:Folic acid, riboflavin, thiamine, and vitamin B-6 status of a group of first-time blood donors. 980 25

Cholestatic jaundice is the major complication of total parenteral nutrition (TPN) in infancy. We have previously shown that the TPN solution is directly toxic to the liver, and that this toxicity appears to be mediated by one or more amino acids. Elevated serum methionine levels, without corresponding increases in its metabolites, suggest that accumulation of this toxic amino acid may cause TPN cholestasis. Nine-week-old rabbits (n = 28) were divided into three groups. The FED group was fed standard rabbit chow ad libitum. The TPN group was not fed and received only i.v. TPN (including methionine 121 mg.kg-1.d-1), and lipids. The EXP group was fed chow ad libitum and received i.v. methionine (121 mg.kg-1.d-1). After 14 d, we evaluated bile flow, bromosulfophthalein excretion, serum liver enzymes, liver histology, and serum amino acid levels. Bile flow was significantly depressed in the TPN and EXP groups compared with FED controls (32.9 +/- 9.4 and 45.7 +/- 14.4 versus 82.9 +/- 13.8). Excretion of the bilirubin analog bromosulfophthalein tended to be delayed by methionine infusion (p = 0.15). Serum liver enzymes (aspartate transaminase, alanine aminotransferase, gamma-glutamyltransferase, and alkaline phosphatase) were normal in all groups. Histologic liver injury in the EXP group was similar to that caused by TPN. Balloon degeneration, and portal inflammation were seen in both groups. Homocysteine, an early metabolite of methionine, was elevated in the TPN and EXP groups compared with FED controls. Intravenous methionine is hepatotoxic. Despite full oral feeding, it produces a depression of bile flow and histologic liver injury similar to that seen with TPN. Elevated homocysteine levels suggests an enzymatic block early in the pathway of methionine metabolism. We believe that methionine may be an important factor in the pathogenesis of TPN cholestasis.
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PMID:Methionine infusion reproduces liver injury of parenteral nutrition cholestasis. 1023 61

Hyperhomocysteinemia in chronic alcoholics has been reported, but it remains unclear whether relatively low alcohol intake compared with the previous reports affects the plasma homocysteine level. To investigate this issue, we performed two studies, a population-based study and an alcohol withdrawal study. An analysis of plasma homocysteine levels in a population of 236 healthy males showed no significant association between alcohol consumption and other tested parameters. In the withdrawal study, the subjects with a history of daily alcohol consumption (81.8 +/- 33.0 g/d, mean +/- SD, 40-150g/d, range) abstained from alcohol for 4 wk. After withdrawal, the levels of serum gamma-glutamyl transpeptidase, aspartate aminotransferase, triglycerides, and high-density lipoprotein cholesterol significantly decreased, but the plasma homocysteine level did not change. These results suggest that alcohol intake, at least as far as the amount of beverages our study subjects consumed, has no effect on the plasma homocysteine level in healthy males.
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PMID:Effect of alcohol intake on the levels of plasma homocysteine in healthy males. 1118 53

Alcoholic liver disease is associated with abnormal hepatic methionine metabolism and folate deficiency. Because folate is integral to the methionine cycle, its deficiency could promote alcoholic liver disease by enhancing ethanol-induced perturbations of hepatic methionine metabolism and DNA damage. We grouped 24 juvenile micropigs to receive folate-sufficient (FS) or folate-depleted (FD) diets or the same diets containing 40% of energy as ethanol (FSE and FDE) for 14 wk, and the significance of differences among the groups was determined by ANOVA. Plasma homocysteine levels were increased in all experimental groups from 6 wk onward and were greatest in FDE. Ethanol feeding reduced liver methionine synthase activity, S-adenosylmethionine (SAM), and glutathione, and elevated plasma malondialdehyde (MDA) and alanine transaminase. Folate deficiency decreased liver folate levels and increased global DNA hypomethylation. Ethanol feeding and folate deficiency acted together to decrease the liver SAM/S-adenosylhomocysteine (SAH) ratio and to increase liver SAH, DNA strand breaks, urinary 8-oxo-2'-deoxyguanosine [oxo(8)dG]/mg of creatinine, plasma homocysteine, and aspartate transaminase by more than 8-fold. Liver SAM correlated positively with glutathione, which correlated negatively with plasma MDA and urinary oxo(8)dG. Liver SAM/SAH correlated negatively with DNA strand breaks, which correlated with urinary oxo(8)dG. Livers from ethanol-fed animals showed increased centrilobular CYP2E1 and protein adducts with acetaldehyde and MDA. Steatohepatitis occurred in five of six pigs in FDE but not in the other groups. In summary, folate deficiency enhances perturbations in hepatic methionine metabolism and DNA damage while promoting alcoholic liver injury.
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PMID:Folate deficiency disturbs hepatic methionine metabolism and promotes liver injury in the ethanol-fed micropig. 1212 4

Methionine metabolism is regulated by folate, and both folate deficiency and abnormal hepatic methionine metabolism are recognized features of alcoholic liver disease (ALD). Previously, histological features of ALD were induced in castrated male micropigs fed diets containing ethanol at 40% of kilocalories for 12 months, whereas in male micropigs fed the same diets for 12 months abnormal methionine metabolism and hepatocellular apoptosis developed. Folate deficiency may promote the development of ALD by accentuating abnormal methionine metabolism. Intact male micropigs received eucaloric diets that were folate sufficient, folate deficient, or each containing 40% of kilocalories as ethanol for 14 weeks. Folate deficiency alone reduced hepatic folates by one half, and ethanol feeding alone reduced methionine synthase, S-adenosylmethionine (SAM), and glutathione (GSH) levels and elevated plasma malondialdehyde (MDA) levels. The combined regimen elevated plasma homocysteine, hepatic S-adenosylhomocysteine (SAH), urinary 8-hydroxy-2-deoxyguanosine (oxy(8)dG), an index of DNA oxidation, and serum aspartate aminotransferase (AST) levels. Terminal hepatic histopathologic characteristics included typical features of steatonecrosis and focal inflammation in pigs fed the combined diet, with no changes in the other groups. Hepatic SAM levels correlated with those of GSH, whereas urinary oxy(8)dG and plasma MDA levels correlated with the SAM:SAH ratio and to hepatic GSH. The results demonstrate the linkage of abnormal methionine metabolism to products of DNA and lipid oxidation and to liver injury. The finding of steatonecrosis and focal inflammation only in the combined diet group supports the suggestion that folate deficiency promotes and folate sufficiency protects against the early onset of methionine cycle-mediated ALD.
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PMID:Folate deficiency, methionine metabolism, and alcoholic liver disease. 1216 45

Trisomy 21 (Down's syndrome) is the most common genetic cause of human mental retardation. In Down's syndrome (DS) patients, deteriorated glucose, lipid, purine, folate and methionine/homocysteine metabolism has been reported. In our study, we used a proteomic approach to evaluate protein expression of enzyme proteins of intermediary metabolism in the brain of Down's syndrome fetuses. In fetal DS brain, we detected increased protein levels of mitochondrial aconitase as well as NADP-linked isocitrate dehydrogenase, decreased protein expression of citrate synthase and cytosolic aspartate aminotransferase. From two spots that corresponded to either pyruvate kinase M1 or M2 isozymes, significant elevation was observed only in one, while the second spot as well as the sum of the spots showed no differences between DS and controls. These results suggest derangement of intermediary metabolism during prenatal development of DS individuals.
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PMID:Proteomic evaluation of intermediary metabolism enzyme proteins in fetal Down's syndrome cerebral cortex. 1244 54


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