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)

In order to establish evidence of serum enzyme activities in toxicological long-term experiments alterations of alanine aminotransferase (ALAT) and aspartate aminotransferase (ASAT) in the serum of rats were investigated after subchronic ethanol pretreatment and following trichloroethylene exposure. Somewhat lower enzyme activities were found in ethanol treated animals than in those who only got water in nearly all cases. Significant ALAT and ASAT decreases occurred after giving higher ethanol concentrations (5% and 10%, v/v) for 30 weeks. It is possible that this fact among other things could be responsible for the only slight enzyme elevations after trichloroethylene in long-term ethanol pretreated rats.
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PMID:Serum enzymes in toxicity of trichloroethylene after subchronic ethanol pretreatment. 386 70

Blood acetate concentration of 51 intoxicated patients was measured and compared to conventional laboratory markers of chronic alcoholism. Mean blood acetate concentration of 23 chronic alcoholics and 17 heavy drinkers was significantly (p less than 0.0005) higher than that of 53 nonalcoholic volunteers or 11 occasional drinkers. Blood acetate level was completely independent of blood ethanol concentration ranging from 0.20 to 2.90 promille. Blood acetate was elevated in 65% of both chronic alcoholics and heavy drinkers. Gammaglutamyltransferase was abnormal only in 35%, aspartate aminotransferase in 21% and mean corpuscular volume in 12% of heavy drinkers. Combination (acetate + gammaglutamyltransferase) correctly detected 87% of alcoholics and 71% of heavy drinkers. During ethanol oxidation the upper normal limit of blood acetate is 0.75 mM. The specificity of increased blood acetate is as high as 92%. Increased blood acetate is indicative for metabolic tolerance to alcohol and it may be so far the most sensitive and specific laboratory marker of chronic alcoholism and heavy drinking.
Alcohol Clin Exp Res
PMID:Increased blood acetate: a new laboratory marker of alcoholism and heavy drinking. 390 14

A self administered questionnaire, the health survey questionnaire, was designed to detect excessive alcohol consumption and mailed to patients who were registered with two general practices. Replies were received from 2572(75%) of 3452 patients. Excessive consumption was taken as 42 units of alcohol per week or more for men and 21 units per week or more for women: 1 unit = approximately 10 g ethanol and is equivalent to a half pint of beer, one glass of wine, or one standard measure of spirits. One hundred and twenty men (11%) and 68 women (5%) were identified by their responses to the questionnaire as excessive drinkers. According to their responses, roughly half of these expressed some concern about their drinking. In the practice where a disease register was kept 18 patients had been recorded as heavy drinkers before the study, and an additional 74 were detected by the questionnaire. Within 12 months after the questionnaire survey three groups of respondents were reviewed: (a) the excessive drinkers, (b) those who indicated concern about drinking but did not exceed the limits for excessive consumption, and (c) a random sample of those who were in neither of these two categories. Patients in these three groups were interviewed in a standard fashion to determine their alcohol consumption. Breath alcohol measurement was also carried out and a blood sample taken for the estimation of mean cell volume, gamma glutamyltranspeptidase activity, and serum aspartate transaminase activity. There were highly significant correlations between estimates of consumption obtained by the questionnaire and those obtained at interview except among the women who were excessive consumers, whose responses to the questionnaire indicated levels of consumption that were much higher than those to which they admitted at interview. Stated weekly consumption at interview that was above the limits set for the study was used as the standard measure for comparing the questionnaire with the other indicators of excessive drinking. The questionnaire had a considerably greater estimated sensitivity in detecting male excessive consumers than any of the blood tests. Among the women it apparently performed less well, although the numbers stating excessive consumption at interview were small. Breath alcohol measurement was positive in only a few of the excessive drinkers. The use of this simple and inexpensive instrument is likely to prove widely acceptable to patients in general practice and should result in a considerable increase in the recognition by general practitioners of patients with excessive alcohol consumption.
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PMID:Use of a questionnaire in general practice to increase the recognition of patients with excessive alcohol consumption. 392 23

Weanling, male Sprague-Dawley rats given 10% ethanol in the drinking water and food ad lib. for up to 8 weeks consumed 17% of their calories as ethanol. The alanine aminotransferase (ALT), aspartate aminotransferase (AST), and liver histology by light microscopy were unaffected by this treatment. Similarly, hepatic microsomal NADPH-cytochrome c reductase, ethylmorphine N-demethylase and benzphetamine N-demethylase activities were also not affected by ethanol consumption. On the other hand, cytochrome P-450 content, aniline hydroxylase activity and acetaminophen metabolism as measured by both the cysteine conjugate and the [3H]acetaminophen covalently-bound to microsomal protein were increased significantly by ethanol consumption. The maximal effect was seen by 6 weeks. The 2- to 3-fold increase in aniline and acetaminophen metabolism, the absence of liver damage, and the similarity in weight gains and caloric intakes for controls and treated animals suggest that the rat on 10% ethanol in the drinking water is a reasonable model for studies of the effect of moderate alcohol consumption on specific biochemical pathways.
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PMID:Studies on the effect of chronic consumption of moderate amounts of ethanol on male rat hepatic microsomal drug-metabolizing activity. 393 44

Male squirrel monkeys fed ethanol (ETOH) at variable doses were used to determine whether alcohol modifies levels of plasma low density lipoproteins (LDL) in addition to increasing high density lipoproteins (HDL). Because we earlier showed that high alcohol consumption enhances lipoprotein cholesterol synthesis, experiments were also performed to further assess whether ETOH alters lipoprotein clearance and plasma transfer processes in vivo. Monkeys were divided into three groups: Controls fed isocaloric liquid diet; and Low and High ETOH animals fed liquid diet with vodka substituted isocalorically for carbohydrate at 12 and 24 of the calories, respectively. High ETOH primates had significantly more LDL lipid and protein while serum glutamate oxaloacetate transaminase was similar for the three groups. Although removal of 3H LDL cholesteryl ester (CE) from the plasma compartment was not affected by dietary ETOH, transfer of LDL CE to HDL was impaired in the High ETOH group suggesting a mechanism for the enlarged circulating pool of LDL. Transfer of 14C HDL CE to lower density lipoproteins was similar for the three groups. However, ETOH at both doses delayed clearance of radiolabeled HDL CE from circulation. Thus besides enhancing synthesis of lipoproteins, ETOH at a moderately high dose (24% of calories) influences lipoprotein levels in primates by modifying lipid transfer processes (LDL) as well as by altering clearance (HDL) without adversely affecting liver function.
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PMID:Ethanol induced alterations in low and high density lipoproteins. 397 32

The level of alanine aminotransferase (ALT) in blood donors has been related to the frequency of posttransfusion hepatitis in recipients. Sixty-seven donors with elevated ALT levels were evaluated to define the duration and significance of the elevation. The ALT level remained elevated in 41 donors (61%) for a mean interval of 9 months. The ALT level was greater than the aspartate aminotransferase in all of the donors. Alcohol intake did not correlate with ALT level. Donors with persistently elevated ALT levels had a significantly higher mean percent ideal body weight (128 +/- 3.9) than donors whose ALT level became normal (116 +/- 3.1). Nine donors with elevated ALT levels for at least 6 months had needle biopsies of the liver. Seven had prominent fatty vacuolization of hepatocytes without evidence of alcoholic hepatitis. One biopsy demonstrated chronic persistent hepatitis. No other cause for the elevated ALT levels could be identified. An overweight male donor with an isolated ALT elevation may need no further investigation unless clinical evaluation suggests a source of liver injury.
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PMID:The persistence and significance of elevated alanine aminotransferase levels in blood donors. 398 3

The effect of variable doses of ethanol on plasma lecithin: cholesterol acyltransferase (LCAT) activity was examined in male, atherosclerosis-susceptible squirrel monkeys over a 12-month period. Primates were divided into three groups: 1) Controls fed isocaloric liquid diet; 2) Low Ethanol monkeys given 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. There were no significant differences between the treatments in serum glutamate oxaloacetate transaminase (SGOT), a measure of liver function. However, plasma LCAT activity (% esterification/min) measured in vitro was significantly reduced in High Ethanol monkeys while cholesterol esterification was elevated in the Low Ethanol group and intermediate in Controls. Similarly, the in vivo appearance of radiolabeled cholesteryl ester in high density lipoproteins (HDL) following the intravenous injection of 3H mevalonolactone was highest in the Low Ethanol primates, intermediate in Controls and significantly lower in monkeys fed the high alcohol diet. In vitro measurement of LCAT enzyme efficiency was similar for the three groups while substrate efficiency was lower in the High Ethanol treatment. Although LCAT activator (apoprotein A-I) was not markedly altered by dietary ethanol and the concentration of LCAT substrates (HDL free cholesterol and phosphatidyl choline) was significantly elevated in the High Ethanol group, subtle modifications in substrate-product composition may account for the observed reduction in cholesterol esterification. These include potential substrate and/or product LCAT inhibition resulting from increased concentrations of plasma free cholesterol, HDL lysophosphatidyl choline, and higher HDL2/HDL3 subfraction ratios, as well as alterations in HDL phospholipid fatty acid profiles in the High Ethanol group. Results from this study provide the first evidence of an anomalous enhancement in LCAT activity in nonhuman primates fed ethanol at 12% of calories and a marked depression in cholesterol esterification at the 24% dose which may be due to substrate alterations and product inhibition prior to overt biochemical evidence of liver dysfunction.
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PMID:Effect of ethanol on lecithin:cholesterol acyltransferase (LCAT) activity. 399 6

1. Incubation of isolated liver cells in a medium containing bicarbonate raises malate concentrations almost sixfold compared with values obtained in a bicarbonate-free phosphate medium. The malate concentration of about 0.3mm in bicarbonate medium is of the same order as the K(m) for malate dehydrogenase. 2. The utilization of ethanol, glyercol and sorbitol was increased by 20-35% in bicarbonate medium. 3. Fluoromalate, a specific inhibitor of malate dehydrogenase and the malate carrier, inhibited or ethanol oxidation by 23%, glycerol uptake by 20% and sorbitol uptake by 42% in bicarbonate medium, but had a much smaller inhibitory action in phosphate medium. In consequence fluoromalate almost abolished the stimulatory effects of bicarbonate on substrate utilization. 4. Difluoro-oxaloacetate, a specific inhibitor of aspartate aminotransferase, had about one-half the inhibitory activity of fluoromalate. The two inhibitors in combination were less effective than fluoromalate by itself. 5. It is concluded that bicarbonate stimulates the utilization of reduced substrates, which are oxidized in the cytoplasmic compartment of the liver cell, by increasing the activity of rate-limiting malate dehydrogenase-dependent intercompartmental hydrogen shuttles. Both malate-oxaloacetate and malate-aspartate systems are involved in these hydrogen-translocation processes.
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PMID:Effects of bicarbonate on intercompartmental reducing-equivalent translocation in isolated parenchymal cells from rat liver. 444 23

31 healthy Thai males, 22 Thai male regular drinkers not suffering from any clinical signs or symptoms of alcoholism, and 52 patients from a neurological hospital in Bangkok suffering from the effects of chronic alcohol consumption were investigated. Alcohol consumption in asymptomatic drinkers ranged from 7 to 134 (median 44) g/d ethanol, and for the patients 22 to 517 (median 197) g/d ethanol, as assessed by questionnaires. The symptomatic alcohol drinkers had consumed alcohol for 2 to 35 years and the hospitalized patients for 5 to 40 years. Only the median levels of serum triglycerides and serum glutamyl transferase (gamma-G) were significantly increased and vitamin B1 deficiency was found with higher frequency in the group of alcohol drinkers without clinical signs compared with the healthy non-alcohol drinkers. Statistically significant correlations were demonstrated in the group of asymptomatic alcohol drinkers only, between alcohol consumption and the Quetelet's index, gamma-G, and alkaline phosphatase levels. Alkaline phosphatase also correlated significantly with gamma-G. In the group of hospitalized patients, compared with healthy males statistically significantly higher median values of systolic and diastolic blood pressure, serum triglyceride, gamma-G, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), alkaline phosphatase, haemoglobin, hematocrit, folate and total protein were found. The median levels of cholesterol, bilirubin, vitamin B2, B6 and B12 in the hospitalized group were lower than, but not significantly different from the other two groups.
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PMID:Alcohol consumption, liver function tests and nutritional status in Thai males. 612 Jan 45

A prospective randomized double-blind trial of (+)-cyanidanol-3 at a dose of 2 g daily (500 mg qds) for six months versus placebo has failed to demonstrate statistically significant clinical, biochemical or histological benefit in patients with biopsy-proven alcoholic liver disease although certain trends were identified. The group receiving the active drug tended to drink more both before and during the trial and had mean serum aspartate aminotransferase (AsT) and gamma-glutamyltranspeptidase (gamma-GT) levels which were higher on admission to the trial. After the fourth week of treatment, the mean serum levels of these enzymes remained consistently lower in the group receiving the active drug. In order to reproduce the beneficial effects of the drug observed in the rat, it is suggested that further trials be conducted with the dosage so far used in man (ca. 20-40 mg/kg daily) increased toward that successfully employed in animal experiments (200 mg/kg daily).
Alcohol Alcohol 1984
PMID:(+)-Cyanidanol-3 for alcoholic liver disease: results of a six-month clinical trial. 614 58


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