Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since red cells transport and metabolize acetaldehyde in vivo, the effects of acetaldehyde on human red cell enzyme activities were studied. Incubation of intact red cells or undiluted red cell lysates at 37 degrees C for 4 h with 1-10 mmol/l acetaldehyde decreased only GOT, GPT and aldolase activities among the 26 enzymes tested. No inhibition occurred at 4 degrees C or when acetaldehyde was incubated with dilute hemolysates. Incubation of lysates with other reducing substrates or with acetate inhibited aldolase but not GOT or GPT. Preincubation of lysates with cyanate or fluoride markedly decreased acetaldehyde-mediated transaminase inhibition but not aldolase inhibition. Addition of pyridoxal phosphate, the vitamin B6 transaminase coenzyme, to GOT and GPT assay mixes did not reverse acetaldehyde-mediated transaminase inhibition. These findings suggest that acetaldehyde-mediated aldolase inhibition results from oxidation of acetaldehyde while transaminase inhibition results from nonoxidative acetaldehyde metabolism. When 100-200 mumol/l acetaldehyde is added to lysates at 2-h intervals and when lysates are incubated with ethanol, alcohol dehydrogenase and an NAD-regenerating system, enzyme inhibition occurs at acetaldehyde levels approaching those seen in vivo. Thus, the role of acetaldehyde-mediated enzyme inhibition in the toxicity of alcohol abuse warrants further study.
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PMID:Effects of acetaldehyde on human red cell metabolism: evidence for the formation of enzyme inhibitors. 341 86

Ethanol metabolism in rat hepatocytes isolated either from the periportal (pp) or the perivenous (pv) area by collagenase gradient perfusion was compared to reveal metabolic factors that could be associated with the development of perivenous alcoholic liver damage. Cells were also isolated from rats given ethanol (E) chronically by addition to the drinking fluid. One group (EM) received in addition the alcohol dehydrogenase inhibitor 4-methylpyrazole, which potentiated the ethanol treatment by causing sustained elevated diurnal blood ethanol levels. Fatty degeneration ensued in only one-third of the E rats but in all of the EM rats. The periportal/perivenous activity distributions of alanine aminotransferase (ALAT) and glutamate dehydrogenase (GLDH) were 2.2 and 0.75, respectively. Both ethanol treatments significantly decreased the ALAT and increased the GLDH activities, but did not change their pp/pv distributions. Ethanol treatment also increased ethanol and acetaldehyde oxidation, but to the same extent in pp and pv cells. The increase was more marked in cells from EM rats despite their more severe liver fatty degeneration. Ethanol incubation also increased the lactate/pyruvate ratio to the same extent in pp and pv cells both from control or ethanol-treated rats. Our results indicate that periportal and perivenous hepatocytes convert ethanol via acetaldehyde to acetate equally well and with similar effects even after chronic ethanol treatment. Consequently, preferential damage of the perivenous area after chronic ethanol intake is not caused by inherent or acquired differences in ethanol metabolism between perivenous and periportal hepatocytes. Rather, sinusoidal gradients only established in the intact liver may exaggerate the metabolic imbalance by ethanol in the perivenous area, thus explaining its greater vulnerability to damage by alcohol abuse.
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PMID:Comparison of ethanol metabolism in isolated periportal or perivenous hepatocytes: effects of chronic ethanol treatment. 390

Elevated serum alanine aminotransferase (ALT) for more than one year was found in 36 (28.8%) of 125 patients on maintenance haemodialysis. In 10 the ALT returned to normal spontaneously but in 26 it remained high. Liver tissue from 21 patients with high ALT and seven with normal ALT was examined. Statistically significant correlations were found between the mean ALT during the year prior to the biopsy and assessments of the lymphocytic infiltration (p less than 0.001), fibrosis (p less than 0.001) and amount of silicone particles in the liver (p less than 0.001). Epithelioid cell granulomata, lobular and portal macrophages and perivenular fibrosis were related to silicone particles. Lymphocytes were not spacially related to the particles; nevertheless, there was a significant correlation between amounts of silicone and lymphocytic infiltration (p less than 0.01). No associations were found between high ALT, hepatitis B serology, serum ferritin, parenchymal siderosis, propensity to fluid overload, alcohol abuse and HLA-B8.
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PMID:Chronic liver disease in haemodialysis patients. 687 29

An isoform of transferrin, carbohydrate-deficient transferrin (CDT) is increased in a high percentage of abusing alcoholics and has been found superior in its specificity compared with other biological markers. We used serum CDT as a screening parameter in 502 patients consecutively admitted to our medical department during a 4-week period. The intake of ethanol during the last 4 weeks was registrated by personal interviews and the mean daily consumption calculated. Serum CDT was measured at admission (CDTect) and compared with gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean corpuscular volume (MCV). Serum CDT detected 18 of 26 (69%) patients who consumed > 50 g ethanol daily. The clinical sensitivity of CDT of detection ethanol consumption > 50 g daily was 69%, compared with 73%, 50%, 35%, and 52% for increased values of GGT, AST, ALT, and MCV, respectively. Altogether, 38 of 476 patients (8%) with a daily ethanol consumption < 50 g also had increased serum CDT levels. The specificity of CDT was 92%, compared with 75%, 82%, 86%, and 85% for GGT, AST, ALT, and MCV, respectively. In the 60 patients who consumed > 10 g ethanol daily, we found a significantly positive correlation between CDT and ethanol consumption (r = 0.52, p < 0.001). A positive correlation was also found between serum transferrin and CDT (r = 0.51, p < 0.001). In conclusion, the specificity of CDT is much higher compared with GGT in detecting alcohol abuse. Some acute and chronic illnesses may increase the serum level of CDT. False-positive CDT levels may be caused by changes in serum transferrin concentration.
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PMID:Carbohydrate-deficient transferrin and other markers of high alcohol consumption: a study of 502 patients admitted consecutively to a medical department. 784 91

Carbohydrate-deficient transferrin (CDT) has previously been reported to be an excellent marker of male alcoholics. Less is known of its efficiency among women and especially of early-phase alcohol abuse in nonselected populations. The present population-based study examined the diagnostic value of CDT among consecutive women, including 13 teetotallers, 135 social drinkers (mean alcohol consumption 45 +/- 34 g/week), and 57 nonalcoholic heavy drinkers (197 +/- 97 g/week). Sixty-two women with a well-documented history of chronic alcoholism (942 +/- 191 g/week) were also studied, as well as 36 pregnant women used as a reference group. Two weeks of abstinence among 11 alcoholics was followed. The CDT (containing part of isotransferrin with pI = 5.7, 5.8, and 5.9) was separated by anion exchange chromatography and assayed by radioimmunoassay. In the whole material, CDT correlated significantly with alcohol consumption (r = 0.43, p < 0.001) but not with conventional markers (gamma-glutamyltransferase, AST, ALT, and mean corpuscular volume). The CDT values of alcoholics (34 +/- 20 units/liter) were significantly (p < 0.001) higher than those of teetotallers (19 +/- 6 units/liter), social drinkers (20 +/- 6 units/liter), or pregnant women (16 +/- 3 units/liter). Heavy drinkers also had higher values (25 +/- 13 units/liter), but the difference did not reach statistic significance. The specificity of CDT was on the level of conventional markers when the cut-off value was increased from 26 to 29 units/liter. At a specificity of 95%, CDT found 19% of the heavy drinkers and 52% of the alcoholics; the best traditional marker, AST, with a specificity of 97%, found 7% and 56%, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Carbohydrate-deficient transferrin as an alcohol marker among female heavy drinkers: a population-based study. 797 1

Data on the prevalence of chronic liver disease, derived from selected series of hospitalized patients or from mortality registers, underestimate the prevalence of chronic liver disease. The Dionysos Study is a cohort study that investigated for the first time the prevalence of chronic liver disease in a general population. All the citizens of two towns in northern Italy, Campogalliano and Cormons, aged 12 to 65 yr were contacted by letter. From March 1991 through March 1993, 6,917 of a total of 10,150 citizens were enrolled (compliance, 69%). The standardized protocol for each enrollee included (a) a color-illustrated food questionnaire on dietary habits and alcohol intake; (b) a detailed medical history, including questions on risk factors for chronic liver disease; (c) a physical examination; and (d) blood tests for AST, ALT, gamma-glutamyltranspeptidase, mean cell volume, platelet count and hepatitis B virus and hepatitis C virus markers. Signs suggestive of chronic liver disease were seen in 21.3% of the subjects, and who then underwent further liver function tests, upper abdominal ultrasonography and, when necessary, liver biopsy. Persistent signs of chronic liver disease were present in 17.5% of the subjects, including 1.1% with cirrhosis and 0.07% with hepatocellular carcinoma. The prevalence rates of hepatitis B virus and hepatitis C virus positivity (second-generation enzyme-linked immunosorbent assay) were 1.3% and 3.2%, respectively. Alcohol abuse was the etiological agent in 23%.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prevalence of chronic liver disease in the general population of northern Italy: the Dionysos Study. 798 43

Anorexia, weight loss, fatigue, symptoms of alcohol withdrawal and hepatomegaly are common early presenting signs and symptoms of alcohol abuse. The clinical diagnosis of alcoholic hepatitis can be made in alcoholics with associated fever, leukocytosis, jaundice and tender hepatomegaly. Associated laboratory abnormalities may include leukocytosis or leukopenia, anemia, a prolonged prothrombin time and elevated liver enzymes, including aspartate amino-transferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and bilirubin. An AST-to-ALT ratio greater than 2 is common in patients with alcoholic hepatitis. Liver biopsy may be required to establish the diagnosis and to identify other pathology, such as cirrhosis. Histologic diagnosis of alcoholic hepatitis requires the presence of liver cell damage, an inflammatory infiltrate and fibrosis. Biopsy-proven cirrhosis with alcoholic hepatitis or a significantly elevated total bilirubin level and prolonged prothrombin time are associated with a worse prognosis. Abstinence from alcohol, nutritional supplementation and corticosteroids are the mainstays of treatment for severe alcoholic hepatitis.
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PMID:Alcoholic hepatitis. 846 12

Two cases of alcoholic cerebellar degeneration with pyramidal sign were reported. Patient 1 with alcohol dependence syndrome was a 46-year-old woman. After the alcohol abuse of about eight years, she complained of gait disturbance. The gait disturbance progressively worsened in about two months and she could not ambulate freely by herself. Neurological examination revealed nystagmus, ataxic and spastic gait, slight weakness and spasticity of the lower extremities, hyperreflexia of the extremities, bilateral Babinski's signs, and incoordination of the lower extremities. Examination of liver function and serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis and dorsal part of the cerebellum. Though neurological signs slightly improved after the admission to our hospital and the abstinence from alcohol abuse, ataxic gait and hyperreflexia of the extremities have continued. Patient 2 was a 58-year-old man. He was a heavy drinker, but was not a patient with alcohol dependence syndrome. After the heavy drinking of about 40 years, he complained of gait disturbance. The gait disturbance had progressively worsened in about four months. Neurological examination revealed ataxic gait, hyperreflexia of the lower extremities, and bilateral Babinski's signs. Laboratory examination revealed slight liver dysfunction with minimal GPT and moderate gamma-GTP elevation. Examination of serum B12 was normal. Cranial CT scan and MRI revealed atrophy of the cerebellar vermis. Though bilateral Babinski's signs disappeared after the abstinence from heavy drinking, ataxic gait and hyperreflexia of the lower extremities have continued. Alcoholic myelopathy without hepatic cirrhosis was rarely reported. In the relation of alcoholic cerebellar degeneration to alcoholic myelopathy, our cases are interesting and important.
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PMID:[Alcoholic cerebellar degeneration with pyramidal sign--in relation to alcoholic myelopathy]. 847 68

We measured serum levels of carbohydrate deficient transferrin (CDT) in 420 subjects: 100 healthy blood donors, 82 healthy employees, 70 abstaining patients with different chronic nonalcoholic liver disease, 16 abstaining patients with alcoholic fatty liver, 50 abstaining patients with alcoholic liver cirrhosis, 25 abusing patients with alcoholic fatty liver, 41 abusing patients with alcoholic liver cirrhosis, and 36 patients with alcohol dependence syndrome with a daily ethanol consumption of 173 +/- 120 g the last 4 weeks before blood was drawn. In controls the serum level of CDT was significantly higher in females compared with males (17.7 +/- 5.1 and 13.7 +/- 3.8 units/liter, respectively), and the upper normal limit was defined as 27 and 20 units/liter. Sixty-two of 102 (60.8%) abusing patients with alcoholic liver disease had increased levels of CDT compared with 1 of 66 abstaining (1.5%) patients with alcoholic liver disease, and 10 of 70 (14.3%) abstaining patients with nonalcoholic liver disease among them 3 with primary biliary cirrhosis and 2 with chronic autoimmune hepatitis. No correlation was found between serum CDT and gamma-glutamyltranspeptidase (GGT), AST, ALT, and mean red cell volume (MCV). The sensitivity and specificity for serum CDT was 61 and 92%, respectively, compared with 85 and 18% for GGT and 70 and 66% for MCV. No advantage was gained by using the CDT/transferrin ratio. Our study confirms that CDT is a specific marker for chronic alcohol abuse, except in few patients with other chronic liver diseases. Serum CDT seems to be a better indicator of abstention than GGT; AST and MCV in patients with alcoholic liver disease. However, in our hands CDT is not so sensitive for alcohol abuse in patients with liver disease as reported earlier in unselected alcoholics.
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PMID:Serum carbohydrate-deficient transferrin as a marker of alcohol consumption in patients with chronic liver diseases. 848 62

Twenty-two South Asian men and 32 European men who had abused alcohol for at least 1.5 years were studied at the time of admission for detoxification to an Alcohol and Drug Dependency unit. The self-confessed average alcohol consumption during the preceding 3 months was similar in the South Asians (mean 383 g/day) and Europeans (mean 435 g/day) but the total duration of alcohol abuse was significantly shorter in South Asians (geometric mean 7.4 years) than Europeans (geometric mean 13.1 years). The geometric mean values for the concentration of carbohydrate-deficient transferrin in the serum were similar in the two ethnic groups. However, the red cell distribution width, the percentages of HbA1a+b, HbA1c and total HbA1 in red cell lysates and the activities of gamma-glutamyl transpeptidase, aspartate aminotransferase and alanine aminotransferase in the serum were all significantly higher in the South Asians than Europeans. The data suggest that South Asian men who abuse alcohol may be more susceptible to alcohol-related liver damage and acetaldehyde-mediated haemoglobin modification than European men who abuse alcohol to a similar extent for a considerably longer period.
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PMID:Ethnic differences in the biological consequences of alcohol abuse: a comparison between south Asian and European males. 855 53


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