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)

The effects on metabolism of the fluorinated dicarboxylic acid, perfluorosuccinate, were examined in hepatocytes from fasted rats. Perfluorosuccinate (5 mM) inhibited gluconeogenesis from lactate by 80% and from pyruvate by 40%. Significant inhibition (up to 30%) occurred at a concentration of perfluorosuccinate of 50 microM. Cellular ATP levels were not affected by perfluorosuccinate, nor was the rate of formation of ketone bodies from palmitate, although the ratio [3-hydroxybutyrate]/[acetoacetate] was increased up to 5-fold relative to the control. An increased concentration of cellular L-malate was measured in the presence of perfluorosuccinate but this did not reflect inhibition of malate transport between the mitochondrial and cytoplasmic compartments. In addition, ethanol oxidation by hepatocytes was inhibited 25% by 1 mM perfluorosuccinate. Ureogenesis from ammonia was relatively insensitive to inhibition by perfluorosuccinate. In cytoplasmic extracts of rat liver, the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase were inhibited 40-50% and 23%, respectively, by 1 mM perfluorosuccinate. The observed metabolic effects of perfluorosuccinate are consistent with inhibition of the activities of phosphoenolpyruvate carboxykinase and aspartate aminotransferase within the cytoplasm.
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PMID:The characterization of perfluorosuccinate as an inhibitor of gluconeogenesis in isolated rat hepatocytes. 277 10

To better define the significance and mechanism of acetaldehyde-mediated transaminase inhibition, acetaldehyde metabolism was studied in rat liver homogenates and cytosols. When either preparation was incubated at 37 degrees with 1.5 mM acetaldehyde for 4 hr, acetaldehyde levels fell rapidly in the first 30 min and little inhibition of aspartate aminotransferase (GOT) or alanine aminotransferase (GPT) resulted. In contrast, incubation with 50 mM ethanol also resulted in a peak acetaldehyde level of 1.0 to 1.5 mM by 2 hr, but this level was then maintained for the next 2 hr and transaminases were inhibited by 20-35%. Sequential addition of low dose (125-250 microM) pulses of acetaldehyde to rat liver preparations resulted in a progressive decrease in the rate of acetaldehyde disappearance. When the pulsing schedule was adjusted accordingly to maintain acetaldehyde levels between 50 and 250 microM for 8 hr, transaminases were again inhibited by 20-40%. Finally, addition of 1-5 mM pyridoxal and pyridoxal 5'-phosphate, aldehydic B6 vitamers, to cytosols 2-4 hr after pulsing with acetaldehyde was begun, almost completely prevented further transaminase inhibition. In contrast, the non-aldehydic B6 vitamers, pyridoxine, pyridoxamine and pyridoxamine 5'-phosphate, did not affect acetaldehyde-mediated transaminase inhibition. These findings suggest that (1) prolonged exposure to low levels of acetaldehyde impairs acetaldehyde metabolism in rat liver homogenates and cytosols; (2) acetaldehyde toxicity may be more dependent on sustained exposure to acetaldehyde than on the peak level of acetaldehyde attained; and (3) aldehydic B6 vitamers can modify on-going acetaldehyde-mediated transaminase inhibition.
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PMID:Inhibition of rat liver transaminases by low levels of acetaldehyde and the pharmacologic effects of B6 vitamers. 281 34

Serum mitochondrial aspartate aminotransferase (mAST) and gamma-glutamyl transpeptidase activities were measured in 303 outpatients upon visits to their general practitioner. Alcohol consumption was evaluated by interview, using a standard questionnaire. Thirty-four patients drank more than 80 g of alcohol per day but none complained of an alcohol-related disease. These 34 heavy drinkers presented a mean serum mAST value which was significantly higher than that of the 269 normal drinkers; however, only 14 out of the 34 (41%) exhibited an increased mAST value. The sensitivity, specificity and predictive positive value of the mAST/tAST ratio were 0.29, 0.77 and 0.13, respectively; the corresponding figures for GGT were 0.5, 0.81 and 0.23, respectively. These results are in sharp contrast with those obtained for mAST activity in a population of hospitalized alcoholics. The explanation may lie in differences in alcohol consumption, in nutritional status and in the frequency of alcohol-related diseases in inpatients as compared to outpatients.
Alcohol Alcohol 1989
PMID:Evaluation of mAST/tAST ratio as a marker of alcohol misuse in a non-selected population. 281 50

Plasma-HDL-cholesterol levels were determined in 104 patients (92 males and 12 females) with a mean age of 43 years (range 20-70 years). All were admitted to a clinic for alcoholics and had a mean drinking history of 13 years with a mean consumption of 48.2 l of pure ethanol per year. There was no correlation between HDL-cholesterol level and the total ethanol consumption in the year before admission or in the month before admission. However, weak negative correlations between HDL-cholesterol and smoking habits (r= -0.26, P less than 0.001) and body weight (r= -0.34, P less than 0.001) were found. In 40 patients the mean HDL-cholesterol level decreased from 1.94 +/- 0.75 mmol/l (SD) at admission to 1.29 +/- 0.36 mmol/l after 16 days of abstinence. Altogether, 33 (31.6%) of 104 patients had a HDL-cholesterol level above our reference value of 2 mmol/l while alanine aminotransferase (ALAT), aspartate aminotransferase (ASAT) and gamma-glutamyltranspeptidase (GGT) were increased in 49, 52.9 and 70.3%, of the cases respectively. Although screening programmes have shown an association between plasma-HDL-cholesterol and the number of drinks consumed per day, no such association could be found in a sample of alcoholics. Decrease of HDL-cholesterol during abstinence, however, seems to be a marker in alcoholics.
Alcohol Alcohol 1985
PMID:Plasma-HDL-cholesterol and estimated ethanol consumption in 104 patients with alcohol dependence syndrome. 286 25

Alcoholic liver cirrhosis is a leading cause of morbidity and mortality in alcohol dependence. A common precursor to cirrhosis is alcoholic hepatotoxicity evident clinically by elevated serum liver enzymes. In this study 50 male patients with significant (greater than two times upper limits of normal) elevation of liver enzymes attending a veterans inpatient alcohol treatment center were matched by age and time since last drink to 50 male veterans without elevated liver enzymes. Patients with elevated liver enzymes were found to be more likely to be daily drinkers, less likely to indulge in binge drinking patterns or have alcoholic blackouts, and showed a trend towards a less severe pattern of alcoholism. Significant gamma glutamyl transferase (GGT) elevations were found in patients consuming an average of 7 beers/day for 5 years, and significant aspartate aminotransferase (AST) elevations were found in patients consuming a threshold of 12 beers/day for 10 years. These findings are consistent with current research suggesting alcoholic cirrhosis is a result of a threshold exposure to alcohol in alcoholics with an additional environmental or genetic risk factor.
Drug Alcohol Depend 1987 Nov
PMID:Risk factors for alcohol hepatotoxicity among male alcoholics. 289 May 7

A study of excessive alcohol consumption was carried out on 2,114 adult somatic outpatients. All patients were evaluated by the following methods: Blood-chemical tests (serum gamma-glutamyltransferase (S-GT), serum aspartate aminotransferase (S-ASAT) and ethanol), patient's and doctor's questionnaires, and analysis of data from psychiatric records, social welfare registers and alcohol ambulatory services. Records from psychiatric clinics detected 48% of the patients. Forty per cent of the alcohol patients had S-GT levels greater than 0.9 mu kat/l. S-ASAT and blood ethanol levels were of little informative value. The doctors recognized excessive consumption (greater than 280 g of ethanol/week). The combination of S-GT and questionnaires to patients and doctors detected 63% of the alcohol patients. Both in epidemiological studies and in clinical practice it seems appropriate to use combinations of different methods to detect patients with underlying alcohol problems.
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PMID:Comparison between different methods of detecting patients with excessive consumption of alcohol. 289 48

Excessive alcohol intake causes bone loss. Alcohol abuse is a commonly associated disorder in femoral neck fractures in men, but little attention is given to such an association in women. Using serum biochemical and haematological markers (mean red cell volume MCV, gamma-glutamyl transpeptidase GGT, aspartate transaminase AST, uric acid UA and triglyceride TG) alcohol abuse was assessed in 14 men and 93 women with non-violent fractures of the hip. Abnormal elevations in one or more of the five test pairs known to correlate with increasing alcohol consumption (GGT/MCV, GGT/AST, AST/MCV, MCV/UA) were found in 7.1% of men, and 11.8% of women. When abnormal results in other test pairs were included the prevalence rose to 14.3% in men and 20.4% in women. These figures are higher than those reported for the general population of elderly people.
Alcohol Alcohol 1988
PMID:Serum biochemical and haematological markers of alcohol abuse in patients with femoral neck and intertrochanteric fractures. 289 45

Twenty-nine patients with active rheumatoid arthritis receiving long-term oral weekly methotrexate (MTX) therapy were studied to determine the extent of their hepatic architectural changes. Liver biopsies (n = 101) were performed in all patients before the initiation of MTX therapy, after 2 years, and annually thereafter (mean duration of therapy 53 months). The hepatic histologic grade (5-point scale) in 25 patients increased (worsened) (mean +/- SEM change 0.84 +/- 1.02; P = 0.001). Fibrosis, confirmed by trichrome staining, developed in 14 of 27 patients (52%). A history of alcohol consumption prior to starting MTX correlated significantly with subsequent worsening of the liver biopsy grade (r = 0.55, P = 0.0054). Alcohol intake prior to study entry, elevated weight at MTX initiation, and dose and duration of MTX were significantly associated with the development of fibrosis. Elevations in serum aspartate aminotransferase levels at 29-53 months of therapy correlated with the increase in hepatic histologic grade at the 3-year biopsy (r = 0.50, P = 0.04) and 4-year biopsy (r = 0.58, P = 0.03). We conclude that long-term MTX therapy in rheumatoid arthritis patients results in a statistically significant worsening in hepatic histologic grade, with common development of mild fibrosis. We do not consider these changes to be clinically significant at present.
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PMID:Liver histology in rheumatoid arthritis patients receiving long-term methotrexate therapy. A prospective study with baseline and sequential biopsy samples. 292 47

Serum activity of angiotensin converting enzyme (ACE) was serially measured in 47 hospitalized chronic alcoholics with liver disease. Compared to healthy controls, ACE activity, on admission, in the serum of alcoholics was significantly elevated (42.5 +/- 16.6 U/ml vs. 32.4 +/- 9.6 U/ml; p less than 0.005). About 36% of the patients had an elevated ACE level exceeding an upper normal value of 42 U/ml (mean +/- SD). In contrast to the rapid normalization of such enzymes as aspartate transaminase (AST), alanine transaminase (ALT) and lactic dehydrogenase (LDH) which represent parenchymal liver cell injury, the activity of ACE remained elevated over a period of 4 weeks even with abstinence. The serum level of ACE was significantly correlated with levels of alkaline phosphatase, gamma-glutamyltranspeptidase and monoamine oxidase, but not with those of AST, ALT and LDH. These data suggest increased ACE activity in alcoholics may be related to the influence of chronic consumption of alcohol on hepatic nonparenchymal systems.
Alcohol
PMID:Mild but prolonged elevation of serum angiotensin converting enzyme (ACE) activity in alcoholics. 302 46

This study examines the hypothesis that there may be a clinically important association between alcohol intake and stroke. Alcohol consumption and the haematological and biochemical markers of alcohol intake were studied in hospital admissions for stroke and compared with community based control subjects from an occupational screening survey. In males, moderate to heavy alcohol consumption (greater than 30 units per week) was associated with an increased relative risk of stroke. Light drinking (less than 30 units per week) was associated with reduced relative risk when compared to teetotallers. The relative risk of stroke in moderate and heavy consumers of alcohol compared with teetotallers was elevated 1.8 times. Similar patterns of risk were present for increasing levels of aspartate transaminase and uric acid. Relative risk was increased for all levels of gamma-glutamyl transferase above the lowest. There was a decrease in relative risk associated with increasing levels of mean erythrocyte cell volume though this did not achieve statistical significance. There were few heavy drinkers among the female cases or controls. We conclude that high alcohol intake may be a significant preventable risk factor particularly among male strokes.
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PMID:A community case-control study of alcohol consumption in stroke. 320 34


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