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)

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.
Alcohol Clin Exp Res
PMID:Erythrocyte aldehyde dehydrogenase activity in alcoholism. 639 4

Plasma, whole blood, and red blood cell selenium levels were determined by spectrofluorometry in 30 patients with chronic heavy ethanol ingestion (group I) and 20 normal controls (group II). Nutritional and general medical evaluations were also performed. The mean plasma selenium level was 0.065 microgram/ml +/- 0.012 (SD) for group I versus 0.100 +/- 0.016 for group II (p less than 0.0001). Whole blood levels were 0.076 microgram/ml +/- 0.011 versus 0.114 +/- 0.015 (p less than 0.0001), and red blood cell levels were 0.092 microgram/ml +/- 0.016 compared with 0.130 +/- 0.025 (p less than 0.0001), respectively. Mean triceps skin fold was 8.2 mm +/- 3.5 for group I males versus 12.3 mm +/- 5.0 (p less than 0.005) for group II males but was not well correlated with whole blood selenium status (r = 0.33). Nutritional parameters of percentage of ideal body weight, midarm muscle circumference, serum albumin, and total lymphocyte count revealed no differences. Mildly elevated serum aspartate aminotransferase and/or alkaline phosphatase values occurred in 53% of alcoholics, but selenium levels in these patients were no different from those with normal liver tests. We conclude that depressed blood selenium levels occur frequently in patients with chronic heavy ethanol ingestion even in the absence of overt malnutrition. Since selenium deficiency can produce a spectrum of organ injury which resembles that associated with chronic alcoholism, the relationship of selenium deficiency to alcohol-induced organ injury deserves further study.
Alcohol Clin Exp Res
PMID:Diminished blood selenium levels in alcoholics. 639 3

Male squirrel monkeys fed ethanol at variable doses were used to assess whether alcohol enhances de novo synthesis of high density lipoprotein (HDL) cholesterol in vivo. Monkeys were divided into three groups: 1) Controls fed isocaloric liquid diet; 2) Low Ethanol monkeys fed liquid diet with vodka substituted isocalorically for carbohydrate at 12% of calories; and 3) High Ethanol animals fed diet plus vodka at 24% of calories. High Ethanol primates had significantly higher levels of HDL nonesterified cholesterol than Control and Low Ethanol animals while serum glutamate oxaloacetate transaminase was similar for the three treatments. There were no significant differences between the groups in HDL cholesteryl ester mass or specific activity following intravenous injection of labeled mevalonolactone. By contrast, High Ethanol monkeys had significantly greater HDL nonesterified cholesterol specific activity with approximately 60% of the radioactivity distributed in the HDL3 subfraction. This report provides the first experimental evidence that ethanol at 24% of calories induces elevations in HDL cholesterol in primates through enhanced de novo synthesis without adverse effects on liver function.
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PMID:Ethanol enhances de novo synthesis of high density lipoprotein cholesterol. 646 61

Lactate dehydrogenase (LDH), succinate dehydrogenase (SDH), aspartate aminotransferase (AAT), glutamate dehydrogenase (GDH), AMP deaminase, ornithine transcarbamylase (OTC), arginase and glutamine synthetase (GS) activities were increased in the kidney of the rat during repeated ethanol loading. The significance of these findings is discussed.
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PMID:Renal ammonia metabolic response in the rat to repeated ethanol loading. 648 7

After prolonged application of ethanol the liver and brain of rats show an appreciable increase in lactate dehydrogenase activity, noticeable lowering of cytoplasmic aspartate and alanine aminotransferase activity, elevation of liver arginine succinate lyase activity with unchanged activities of other enzymes of the ornithine cycle (ornithine carbamoyltransferase and arginase), reduction of glutamate and malate dehydrogenase and mitochondrial aspartate aminotransferase activity in brain tissue. Concurrent application of ethanol and pyridoxine normalizes the effect of ethanol on liver arginine succinate lyase and on brain tissue lactate and malate dehydrogenase, mitochondrial and cytoplasmic aspartate aminotransferase and alanine aminotransferase.
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PMID:[Enzyme activity changes in chronic alcoholic intoxication and the simultaneous administration of pyridoxine]. 689 33

The subcellular distribution of metabolites involved in the transfer of reducing equivalents across the mitochondrial membrane was studied in perfused livers from fed rats. A tenfold increase in the flux rate of the malate-aspartate shuttle and the inhibition of the citrate cycle due to ethanol oxidation, were reflected by characteristic changes in the cytosolic and mitochondrial concentrations of malate, 2-oxoglutarate, aspartate, glutamate and citrate. The data suggest that the malate-aspartate shuttle is triggered by a decrease in the cytosolic oxaloacetate concentration which, due to the cytosolic aspartate aminotransferase equilibrium, leads to an increased efflux of 2-oxoglutarate and aspartate from the mitochondria in exchange for malate and glutamate, respectively. The first site at which the citrate cycle is inhibited appears to be the level of 2-oxoglutarate oxidation.
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PMID:Changes in the subcellular distribution of metabolites due to ethanol oxidation in the perfused rat liver. 722 78

Hepatic injury in alcoholics due to intake of acetaminophen (APAP or acetylparaaminophenol) with therapeutic intent has been reported, but the extent of the phenomenon is not clear, pertinent details of the association remain insufficiently clarified, and the importance of the phenomenon is not widely appreciated. The present report describes 67 patients who developed hepatic injury after ingestion of APAP with therapeutic intent. All were regular users of alcohol. Sixty-four percent of the patients were considered to be "alcoholic" or reported intakes greater than 80 g/d, 35% took 60 g/d or less, and the remainder were vague in their reporting. Doses of APAP were in the "nontoxic" range ( < 6 g/d) in 60% of the group, within the recommended range ( < 4 g/d) in 40%, and at 4.1 to 6 g/d in 20%. Characteristic feature was the towering level reached by aspartate transaminase (AST) with figures ranging from 3,000 to 48,000 IU in more than 90% of cases. Almost 20% of the patients died. The data on these patients were similar to 94 cases of injury from APAP taken with therapeutic intent reported in the literature. This study provides further evidence of hepatic injury in regular uses of alcohol, especially chronic alcoholics, who take APAP with therapeutic intent. Susceptibility is presumably caused by induction of cytochrome P-4502EI by ethanol and by depletion of glutathione (GSH) because of the effects of alcohol, the malnutrition often associated with alcoholism, and the depletion associated with chronic use of APAP and impaired glucuronidation caused by fasting perhaps as well. The syndrome of liver injury is distinctive, marked by uniquely elevated levels of AST, and poses a significant threat.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure. 765 81

We investigated whether bile salts (BS) with different hydrophobic-hydrophilic properties interact with ethanol on bile secretion, enzyme (aspartate transaminase [AST], lactate dehydrogenase [LDH]) release in the perfusate, liver ultrastructure, and vesicular exocytosis in the isolated perfused rat liver. Ethanol (0.1 or 1%) promoted a rapid decrease of bile flow and BS secretion in livers perfused with taurocholate (TCA), the physiologic BS in the rat (-28% decrease of baseline values with 0.1% and -34% with 1% ethanol). The inhibitory effect of ethanol on bile flow and BS secretion was significantly (P < .02) attenuated by perfusing liver with the hydrophilic BS, tauroursodeoxycholate (TUDCA), and it was exacerbated (P < .02) by perfusion with the hydrophobic BS, taurodeoxycholate (TDCA). The release of AST and LDH in the perfusate was unaffected by 0.1% ethanol, but increased threefold to fivefold by 1% ethanol in TCA-perfused livers. This cytolitic effect of ethanol was not observed in TUDCA-perfused livers, but it was enhanced (P < .03) by perfusion with TDCA. No ultrastructural abnormalities were found in either TCA- or TUDCA-perfused livers, with or without 1% ethanol. Only minimal changes were found in livers perfused with TDCA alone, but, in the presence of TDCA, 1% ethanol induces marked mitochondrial damage. The biliary excretion of the fluid phase marker horseradish peroxidase was inhibited by ethanol, an effect reversed by TUDCA (P < .02) and exacerbated by TDCA (P < .04). In conclusion, this study demonstrates that hydrophilic BS such as TUDCA counteract the inhibitory effect of ethanol on bile secretion and vesicular exocytosis as well as the ethanol-induced cytolitic effect in the isolated perfused rat liver. In the presence of hydrophobic BS such as TDCA, the exposure to ethanol promotes a marked inhibition of bile secretion and vesicular exocytosis as well as prominent mitochondrial damage.
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PMID:Functional and ultrastructural features of ethanol/bile salts interaction in the isolated perfused rat liver. 770 87

We investigated the effects of the hapten trinitrobenzenesulfonic acid instilled into the rat biliary tree. The study included three groups of animals that received a single intracholedochal injection of either saline, 10% ethanol or 10 mg trinitrobenzenesulfonic acid dissolved in 10% ethanol. A fourth group of rats was subjected to common bile duct ligation and was used as control for biliary obstruction. Liver and biliary tract dysfunction was assessed 1, 10, 20 and 30 days after treatment by serum aspartate aminotransferase, alkaline phosphatase and bilirubin, and by histopathological examination of liver slices. By day 10, saline- or ethanol-treated rats did not show changes in the biochemical parameters, and light microscopy revealed no alterations. In contrast, rats treated with trinitrobenzenesulfonic acid showed significant increases in all serum markers throughout the study period. Inflammatory cell infiltrates were seen in portal areas and around bile ducts, indicating pericholangitis. Some rats presented with dilatation of extrahepatic biliary ducts; ductal proliferation and thin porto-portal fibrotic septa were observed in these cases. Bile duct ligation also induced ductal proliferation and fibrosis in all cases, but pericholangitis was not prominent. Retrograde cholangiograms in trinitrobenzenesulfonic acid rats showed distortion of the intra- and extrahepatic biliary tree. In conclusion, chronic cholangitis may be consistently induced in rats by a single intracholedochal administration of trinitrobenzenesulfonic acid.
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PMID:Induction of chronic cholangitis in the rat by trinitrobenzenesulfonic acid. 779 Jul 10

The use of herbal and other "natural" health products by healthy and ill people is more common than is appreciated by many health care providers. Since most of these substances are not categorized as medicines, they are exempt from U.S. Government approval processes, and are essentially uncontrolled. In this article we describe a patient who developed painless jaundice, fatigue, and pruritus after taking chaparral tablets, 160 mg/day, for approximately 2 months. Serial liver biopsies and serum chemistries documented severe cholestasis and hepatocellular injury, i.e., a severe cholangiolitic hepatitis. Serum enzyme levels were markedly elevated: alk. phos. to four-fold, alanine aminotransferase and aspartate aminotransferase to 25-fold, total bilirubin to 30-fold, and gamma-glutamyl transpeptidase to 35-fold. Endoscopic retrograde cholangiopancreatography showed smooth, but severely narrowed biliary ducts without sclerosing cholangitis, distal obstruction, tumor, or stenosis. The diagnosis remained in doubt until the publication of two cases of chaparral hepatotoxicity. Because of the similarity of our patient's illness to those cases we concluded that chaparral was almost certainly the cause. Chaparral, also known as creosote or greasewood, is used by some practitioners to treat a diverse group of ailments including ethanol withdrawal. This report should heighten the awareness by primary care physicians and gastroenterologists that any chaparral herbal preparation is a potential hepatotoxin that can lead to serious illness.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cholestatic hepatitis after ingestion of chaparral leaf: confirmation by endoscopic retrograde cholangiopancreatography and liver biopsy. 780 38


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