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)

Since ethanol consumption decreases hepatic aminotransferase activities in vivo, mechanisms of ethanol-mediated transaminase inhibition were explored in vitro using mitochondria-depleted rat liver homogenates. When homogenates were incubated at 37 degrees with 50 mM ethanol for 1 hr, alanine aminotransferase decreased by 20%, while aspartate aminotransferase was unchanged. After 2 hr, aspartate aminotransferase decreased by 20% and by 3 hr, alanine and aspartate aminotransferases were decreased by 31 and 23%, respectively. Levels of acetaldehyde generated during ethanol oxidation were 525 +/- 47 microM at 1 hr, 855 +/- 14 microM at 2 hr, and 1293 +/- 140 microM at 3 hr. Although inhibition of alcohol oxidation with methylpyrazole or cyanide markedly decreased ethanol-mediated transaminase inhibition, neither incubation with acetate nor generation of reducing equivalents by oxidation of lactate, malate, xylitol, or sorbitol altered the activity of either enzyme. However, semicarbazide, an aldehyde scavenger, prevented inhibition of both aminotransferases by ethanol. Moreover, incubation with 5 mM acetaldehyde for 1 hr inhibited alanine and aspartate aminotransferases by 36 and 26%, respectively. Cyanamide, an aldehyde dehydrogenase inhibitor, had little effect on ethanol-mediated transaminase inhibition. Thus, metabolism of ethanol by rat liver homogenates produces transaminase inhibition similar to that described in vivo and this effect requires acetaldehyde generation but not acetaldehyde oxidation. Since addition of pyridoxal 5'-phosphate to assay mixes did not reverse ethanol effects, aminotransferase inhibition does not result from displacement of vitamin B6 coenzymes.
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PMID:Evidence for the generation of transaminase inhibitor(s) during ethanol metabolism by rat liver homogenates: a potential mechanism for alcohol toxicity. 366 1

Erythrocyte aldehyde dehydrogenase activity was determined in 44 chronic alcoholic patients within 18-36 hr after discontinuation of chronic alcohol intake and in 20 nonalcoholic controls. The enzyme activity was decreased to 4.98 +/- 0.52 mlU/mg of protein in the alcoholics as compared with a value of 8.25 +/- 1.29 mlU/mg of protein in the controls (p less than 0.05). The level of the enzyme activity did not correlate significantly with the daily quantity of alcohol consumption or the degree of liver injury reflected in elevations of serum aspartate aminotransferase. Repeat determination in 23 of the alcoholics after 2 weeks of supervised abstinence in an inpatient unit resulted in an increase in the enzyme activity to control levels. These findings show that the decreased activity of erythrocyte aldehyde dehydrogenase which occurs in association with alcohol ingestion is not an inherent characteristic of alcoholism.
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PMID:Erythrocyte aldehyde dehydrogenase activity in alcoholism. 639 4

The development of reliable diagnostic tools for assessing alcoholism and harmful alcohol consumption is an utmost necessity for the success of efforts to prevent and treat alcohol-induced damage to both individuals and to society. A multinational study is underway to aid in the development of biological screening tools (state markers) which can, with good sensitivity and specificity, identify problem drinkers. To attain this goal information needs to be available on an individuals's drinking history and habits and related factors. A detailed instrument has been developed to obtain this information. The second goal of the study was to begin to develop diagnostic 'trait markers' which provide biological information on genetically determined predisposing and protective factors in the development of alcoholism. The developed questionnaire also provides background information on subject characteristics necessary for the development of trait markers. Centres will assay the obtained biological samples for 'traditional' and newly identified state markers of excessive alcohol consumption. These will include methanol measurements, gamma-glutamyltransferase, aspartate aminotransferase, carbohydrate-deficient transferrin, serotonin metabolite ratios, and erythrocyte aldehyde dehydrogenase. DNA obtained from the lymphocytes of subjects will be assayed for polymorphisms of alcohol- and aldehyde-metabolizing enzymes and dopamine receptor polymorphisms which can provide insights into protective and predisposing factors in alcoholism. The platelet enzymes, monoamine oxidase and adenylyl cyclase, will be assayed to assess the relationships between these putative trait markers and the genetic and environmental factors contributing to the aetiology of alcoholism. The current report is meant to introduce the study design and present a portion of the preliminary data gathered in the process of establishing this research programme.
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PMID:Biochemical markers of alcohol use and abuse: experiences from the Pilot Study of the WHO/ISBRA Collaborative Project on state and trait markers of alcohol. International Society for Biomedical Research on Alcoholism. 910 7

In Asians from the Pacific rim countries, alcohol sensitivity has been attributed mainly to a highly prevalent polymorphism in low Km aldehyde dehydrogenase (ALDH2). Chronic alcohol abuse may accelerate or aggravate the liver injury in chronic hepatitis C virus (HCV)-infected subjects. In this study, we examined the relationships among alcohol intake, ALDH2 genotypes, and liver injury in a high HCV-prevalent Japanese native island population. The ALDH2 genotypes are significantly associated with drinking habits. In HCV RNA positive subjects, serum alanine aminotransferase (ALT), as well as aspartate transaminase (AST) and gamma-glutamyl transpeptidase (GGT), were significantly higher in habitual drinkers than in nonhabitual drinkers. In male habitual drinkers, the ALDH2*1/*1 subjects had higher liver necroinflammatory scores than the ALDH2*1/*2 subjects in all groups classified as: I, anti-HCV-seronegative; II, anti-HCV-seropositive with negative HCV RNA; and III, HCV RNA positive, although scores for the latter two groups were not statistically significant because of limited sample size. It was suggested that the liver function might be affected by the interaction between the ALDH2 genotypes and alcohol intake. These findings indicate that HCV-infected ALDH2*1/*1 habitual drinkers are the major target for the prevention of alcoholic liver diseases.
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PMID:Effects of alcohol intake and low Km aldehyde dehydrogenase on hepatic function in a high hepatitis C virus-prevalent Japanese island population. 1023 13

A highly prevalent, atypical genotype in low Km aldehyde dehydrogenase (ALDH2) may influence alcohol-induced liver injury because of higher production of acetaldehyde in the liver. In the present study, we examined relationships between the ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers. Study subjects were 385 male workers in a metal plant in Japan, who were free from hepatic viruses and did not have higher aminotransferase activities (<100). The subjects completed a questionnaire on alcohol drinking habits and other lifestyles. The ALDH2 genotype was determined by the PCR method followed by restriction-enzyme digestion. In the moderately and heavily drinking groups, those with ALDH2*1/*2 exhibited significantly lower levels than those with ALDH2*1/*1 for all three parameters of liver function, whereas no such differences were observed in the least-drinking group. Multiple linear-regression analysis, adjusting for age, obesity, and smoking habits, revealed that aspartate aminotransferase activity was positively associated with alcohol intake only in those with ALDH2*1/*1. On the other hand, alanine transferase activity was negatively associated with alcohol intake only in those with ALDH2*1/*2. The present study indicates that effects of alcohol intake on liver-function biomarkers are likely to be modified by the ALDH2 genotype in adult males.
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PMID:The ALDH2 genotype, alcohol intake, and liver-function biomarkers among Japanese male workers. 1094 5

Groups of patients suffering alcoholism and narcomania were examined for the effect of intoxication on the blood serum enzymes of mainly liver origin: alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), aspartate aminotransferase (AST), alanine aminotransferase (ALT), as well as on thymol test. It has been shown that in patients with the first stage of alcoholism one could observe only functional disturbances in the liver: the increase of ADH activity which evidences for the induction of its synthesis. In patients with the first stage of opium narcomania one can record total hyperenzymenia, decrease of de-Rimis coefficient at the expense of more considerable increase of ALT activity than that of AST, as well as the sharp increase of thymol test--these are the signs of destructive and metabolic disturbances in the liver. In patients with the second stage of alcoholism one can observe the decrease of ALDH activity under the increase of ADH, AST, ALT activity and high thymol test-these are the signs of toxical hepatitis. Destructive and metabolic changes increase in the liver in the patients with the second stage of narcomania.
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PMID:[Comparative analysis of the effects of alcoholism and opium addiction on liver function]. 1139 20

A genetic approach was cited for species detection of the ameba genus Naegleria using allozyme electrophoresis to characterize the trophozoite stage of three strains of Naegleria fowleri isolated from patients with primary amebic meningoencephalitis, five thermophilic (45 degrees C) Naegleria spp isolated from natural water sources in the Taling Chan district, and a reference control strain, Naegleria fowleri CDC VO 3081. Isoenzymes of ameba whole-cell extracts were analyzed by vertical polyacrylamide slab gel electrophoresis to determine whether there was any correlation between different strains of the ameba. The results showed that five out of fifteen enzymes; aldehyde oxidase (ALDOX), aldolase (ALD), a-glycerophosphate dehydrogenase (a-GPDH), xanthine dehydrogenase (XDH), and glutamate oxaloacetate transaminase (GOT), were undetectable in the pathogenic strains, while the other enzymes; esterase (EST), fumerase (FUM), glucose-6-phosphate dehydrogenase (G-6-PDH), glucose phosphate isomerase (GPI), isocitate dehydrogenase (IDH), lactate dehydrogenase (LDH), leucine aminopeptidase (LAP), malic enzyme (ME), glucose phosphomutase (GPM), and malate dehydrogenase (MDH), were detected. Naegleria fowleri strains were biochemically the most homogeneous. They showed intraspecific isoenzyme variation that allowed them to be grouped. In contrast, the allozyme patterns (EST 1-7, IDH) of Naegleria spp isolated from the environment showed interspecific isoenzyme variations from the pathogenic Naegleria strain. In conclusion, this study recognized the zymograms of the Naegleria fowleri strains were heterogenically different from the thermophilic 45 degrees C Naegleria spp isolated from the environment.
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PMID:Zymogram patterns of Naegleria spp isolated from natural water sources in Taling Chan district, Bangkok. 1569 Nov 24

Deficiencies in mitochondrial low-Km aldehyde dehydrogenase (ALDH2) activity, and consequently high blood acetaldehyde levels, have been suggested to relate to various diseases in Japanese, including esophageal cancer. In the present study, 200 men aged 35-59 years randomly selected from an occupational population were analyzed for the association of ALDH2 genotypes and cytochrome P450-2E1 (CYP2E1) genotypes with the urinary excretion of acetaldehyde (which is bound to some chemicals in the urine) and with common alcohol-related health consequences. Urinary acetaldehyde excretion was increased, reflecting increased alcohol consumption even in this moderate alcohol-consuming population. Neither the ALDH2 nor the CYP2E1 genotypes showed significant influence on the elevation of urinary acetaldehyde excretion. Neither these genotypes nor urinary acetaldehyde concentration significantly affected blood pressure, serum aspartate aminotransferase and gamma-glutamyl transferase activities, or serum HDL-cholesterol and lipid peroxide concentrations. It was concluded that acetaldehyde accumulates in moderate alcohol consumers irrespective of ALDH2 and CYP2E1 genotype, and that the implications of these genotypes and acetaldehyde accumulation in terms of common alcohol-related health consequences were obscure. The results also suggest that the carcinogenicity of acetaldehyde on esophageal mucosa depends greatly upon repeated exposure to high blood acetaldehyde, even through transient rather than chronic exposure.
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PMID:ALDH2 and CYP2E1 genotypes, urinary acetaldehyde excretion and the health consequences in moderate alcohol consumers. 1636 83

The present study investigates the hepatoprotective effect of fenugreek seed polyphenolic extract (FPEt) against ethanol-induced hepatic injury and apoptosis in rats. Chronic ethanol administration (6 g/kg/day x 60 days) caused liver damage that was manifested by the elevation of markers of liver dysfunction--aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), lactate dehydrogenase (LDH), bilirubin and gamma-glutamyl transferase (GGT) in plasma and reduction in liver glycogen. The effects on alcohol metabolizing enzymes such as alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) were studied and found to be altered in the alcohol-treated group. Ethanol administration resulted in adaptive induction of the activities of cytochrome p450 (cyt-p-450) and cytochrome-b5 (cyt-b5) and reduction in cytochrome-c-reductase (cyt-c-red) and glutathione-S-tranferase (GST), a phase II enzyme. Further, ethanol reduced the viability of isolated hepatocytes (ex vivo) as assessed by the trypan blue exclusion test and increased hepatocyte apoptosis as assessed by propidium iodide staining (PI). Treatment with FPEt restored the levels of markers of liver injury and mitigated the alterations in alcohol metabolizing and detoxification enzymes and the electron transport component cytochrome-c reductase. Increased hepatocyte viability and reduced apoptotic nuclei were observed in FPEt-treated rats. These findings demonstrate that FPEt acts as a protective agent against ethanol-induced abnormalities in the liver. The effects of FPEt are comparable with those of a known hepatoprotective agent, silymarin.
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PMID:Fenugreek (Trigonella foenum graecum) seed polyphenols protect liver from alcohol toxicity: a role on hepatic detoxification system and apoptosis. 1748 88

Molybdenum is an essential trace micronutrient element that plays an important role in animal and plant physiology. Molybdenum is a constituent of at least three mammalian metalloflavoproteins: xanthine oxidase, aldehyde oxidase and sulphite oxidase. In the present study, the hepatoprotective potential of sodium molybdate was investigated against carbon tetrachloride (CCl(4))-induced liver damage in rats. Administration of CCl(4) increased the serum alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase levels in rats and reduced levels of the antioxidant enzymes superoxide dismutase and catalase in the liver. Treatment with sodium molybdate significantly attenuated these changes to nearly undetectable levels. The histopathological changes induced by CCl(4) were also significantly attenuated by sodium molybdate treatment. Therefore, the results of this study suggest that sodium molybdate can protect the liver against CCl(4)-induced oxidative damage in rats, and this hepatoprotective effect might be attributable to its modulation of detoxification enzymes and/or its antioxidant and free radical scavenger effects.
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PMID:Protective effects of sodium molybdate on carbon tetrachloride-induced hepatotoxicity in rats. 2127 81


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