Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.1.1.1 (alcohol dehydrogenase)
 9,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Human and rat O6-methylguanine transferase (O6MeGT) are inhibited in vitro by ethanol at concentrations of 10 to 50 mM and by acetaldehyde, the first metabolite of ethanol, at concentrations as low as 0.01 microM. Several other enzymes, including glyceraldehyde-3-phosphate dehydrogenase and yeast alcohol dehydrogenase, which like O6MeGT have cysteines in their active sites, were not inhibited by acetaldehyde at the levels that inhibited O6MeGT. Disulfiram, an acetaldehyde dehydrogenase inhibitor, enhanced the inhibitory effect of ethanol in vivo. These results indicate that the inhibitory effect of ethanol on O6MeGT activity is mediated primarily via its metabolite, acetaldehyde.
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PMID:In vitro and in vivo inhibitory effect of ethanol and acetaldehyde on O6-methylguanine transferase. 336 37

Rates of reduction of acetaldehyde and pyruvate catalyzed by alcohol dehydrogenase and lactate dehydrogenase have been estimated in isolated hepatocytes from rats metabolizing ethanol and [2-3H]lactate. The concentration of the substrates of the two dehydrogenases were varied by addition of fructose and cyanamide. Calculation of the rates are based on the detritiation pattern of lactate and the labelling pattern of ethanol and glucose. The rate of acetaldehyde reduction increased with the concentration of acetaldehyde and ranged from 1-20 mumol/min ml cells. Net ethanol oxidation was decreased only under conditions with a high rate of reduction of acetaldehyde. The results suggest that the rate of net ethanol oxidation is determined by the activity of acetaldehyde dehydrogenase relative to that of alcohol dehydrogenase.
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PMID:Rate determining factors of ethanol oxidation in hepatocytes from starved and fed rats: effect of acetaldehyde concentration on the rate of NADH oxidation catalyzed by alcohol dehydrogenase. 342 94

Mutants of Escherichia coli resistant to chloroethanol or to chloroacetaldehyde were selected. Such mutants were found to lack the fermentative coenzyme A (CoA) linked acetaldehyde dehydrogenase activity. Most also lacked the associated fermentative enzyme alcohol dehydrogenase. Both types of mutants, those lacking acetaldehyde dehydrogenase alone or lacking both enzymes, mapped close to the regulatory adhC gene at 27 min on the E. coli genetic map. The previously described acd mutants which lack acetaldehyde dehydrogenase and which map at 63 min were shown to be pleiotropic, affecting respiration and growth on a variety of substrates. It therefore seems likely that the structural genes for both the acetaldehyde and alcohol dehydrogenases lie in the adhCE operon. This interpretation was confirmed by the isolation of temperature sensitive chloracetaldehyde-resistant mutants, some of which produced thermolabile acetaldehyde dehydrogenase and alcohol dehydrogenase and were also found to map at the adh locus. Reversion analysis indicated that mutants lacking one or both enzymes carried single mutations. The gene order in the adh region was determined by three point crosses to be trp-zch::Tn10-adh-galU-bglY-tyrT-chlC.
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PMID:The use of suicide substrates to select mutants of Escherichia coli lacking enzymes of alcohol fermentation. 355 Mar 85

The existence of three different proteins exhibiting NAD-dependent acetaldehyde dehydrogenase activity was confirmed in Alicaligenes eutrophus. The fermentative alcohol dehydrogenase, which also exhibits acetaldehyde dehydrogenase activity, is one of these proteins. The other two proteins were purified from A. eutrophus N9A mutant AS4 grown on ethanol applying chromatography on DEAE-Sephacel and triazine-dye affinity media. Acetaldehyde dehydrogenase II, which amounts to about 14% of the total soluble protein in cells grown on ethanol, was purified to homogeneity. The relative molecular masses of the native enzyme and of the subunits were 195,000 or 56,000, respectively. This enzyme exhibits a high affinity for acetaldehyde (Km = 4 microM). Acetaldehyde dehydrogenase I amounts only to less than 1% of the total soluble protein. The relative molecular masses of the native enzyme and of the subunits were 185,000 and 52,000, respectively. This enzyme exhibits a low affinity for acetaldehyde (Km = 2.6 mM). Antibodies raised against acetaldehyde dehydrogenase II did not react with acetaldehyde dehydrogenase I. Two different strains, A. eutrophus N9A mutant AS1, which represents a different mutant type and can utilize both ethanol or 2,3-butanediol, and the type strain of A. eutrophus (TF93), which can utilize ethanol, form two acetaldehyde dehydrogenases during growth on ethanol, too. As in AS4, one of these enzymes from each strain amounted to a substantial portion of the total soluble protein in the cells. These major acetaldehyde dehydrogenases were purified from both strains; they resemble acetaldehyde dehydrogenase II isolated from AS4 in all relevant properties. Antibodies against the enzyme isolated from AS4 gave identical cross-reactions with the enzymes isolated from AS1 and TF93.
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PMID:Three different proteins exhibiting NAD-dependent acetaldehyde dehydrogenase activity from Alcaligenes eutrophus. 365 4

Individual and racial differences in response to alcohol and with respect to alcoholism have strong genetic predispositions. Most studies on the actual genetic determinants have concentrated on the isozymes of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ALDH), the two enzymes of the primary pathway of alcohol metabolism. Although few "activity" variants (associated with mutations in the structural genes) of the two enzymes are known to exist in susceptible groups, these observations do not offer an adequate explanation for the observed variability in response to alcohols in the population. Some recent studies have reported alterations in the specific activity of the two enzymes following exposure to alcohol for different lengths of time in man, rat, and mice. The induction-repression so observed is hypothesized to be regulated by one or more inducibility genetic elements (IGE) associated with the structural loci of the two enzymes. Variability in IGE will permit a genotype (individual) specific response in ADH and ALDH specific activity when challenged with a given level of alcohol. Considering the relative toxicity of acetaldehyde, the primary metabolite of this pathway, the resistant individuals would be expected to show ALDH induction. Conversely, the susceptible individuals should respond to alcohol by ALDH repression. The ability of an individual to show induction or repression following alcohol ingestion will depend on his or her IGE genotype(s) associated with specific enzyme loci. Also, the degree of polymorphism at these loci would be expected to be extensive and yet population and race specific. Once experimentally established, this approach could have important implications in screening, counselling, prevention, and in novel approaches to treatment.
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PMID:Variability in the effect of alcohol on alcohol metabolizing enzymes may determine relative sensitivity to alcohols: a new hypothesis. 380 71

In alcoholic patients with fatty liver the activity of cytosolic, but not of mitochondrial, acetaldehyde dehydrogenase was lower than in controls. Sequential studies in abstaining alcoholics showed that the cytosolic acetaldehyde dehydrogenase activity remained low, although the previously low activity of alcohol dehydrogenase returned to normal values. It is suggested that reduced cytosolic acetaldehyde dehydrogenase activity may represent a primary defect in alcoholism and is, in part, the cause of the abnormal acetaldehyde metabolism in alcoholic patients. Isoelectric focusing showed distinct isoenzymes of acetaldehyde dehydrogenase in the liver cytosolic and mitochondrial fractions. A survey of eight control subjects and twenty alcoholic patients showed no evidence of a missing or abnormal enzyme in the alcoholic group.
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PMID:Role of hepatic acetaldehyde dehydrogenase in alcoholism: demonstration of persistent reduction of cytosolic activity in abstaining patients. 612 41

Effects of acute and chronic alcohol intoxication on activities of arginase, alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (AcDH) were studied in rat liver, brain and kidney tissues. Alcohol intoxication altered both ureotelic (liver) and non-ureothelic (brain, kidney) arginase activity. The arginase activity in all the tissues studied was increased in chronic alcohol intoxication. Elevation in the arginase activity in liver tissue indicates that the urea cycle is activated as well as that hyperproduction of glutamic acid in brain may occur. Specific inhibitory effects of ethanol and acetaldehyde might be responsible for alterations of the arginase activity in all the tissues studied in acute alcohol intoxication. In vitro acetaldehyde at 5 X 10(-6) M concentration inhibited the arginase activity in partially purified preparations of brain and kidney tissues by 40-50% and of liver tissue--by 10-15%; 10% ethanol inhibited the liver enzyme by 90% and affected only slightly the activity of brain arginase.
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PMID:[Arginase activity in various tissues of rats in alcohol intoxication]. 635 55

In chronic alcohol intoxication activity of alcohol-oxidizing systems in liver tissue was not distinctly altered as shown by estimation of alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (AcDH) activities, whereas the arginase activity was increased 1.5-2-fold. At the same time, the activities ADH, AcDH and arginase tended to decrease in acute alcohol intoxication of slight and middle degree. These alterations in the enzymatic activity were more pronounced in acute intoxication occurring simultaneously with chronic alcoholization. Lethal doses of alcohol caused a decrease in ADH and AcDH activities but did not affect the arginase activity.
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PMID:[Effect of alcohol intoxication on activity of enzymes in ethanol oxidation and on arginase activity in rat liver]. 635 53

Acute alcoholic hepatitis is characterized by infiltration of the liver parenchyma with polymorphonuclear leukocytes. As a possible explanation for this phenomenon, we have found that ethanol stimulates cultured rat hepatocytes to generate potent chemotactic activity. Hepatocytes (greater than 99% pure), isolated from the livers of Sprague-Dawley rats, responded to incubation with ethanol (2.0-10 mM) by releasing chemotactic activity for human polymorphonuclear leukocytes into culture supernatants in a time- and concentration-dependent fashion. Chemotactic activity was maximal after incubation of hepatocytes with 10 mM ethanol for 6 h. It was undetectable in the absence of ethanol and was reduced in the presence of either the alcohol dehydrogenase inhibitor, 4-methylpyrazole, or the acetaldehyde dehydrogenase inhibitor, cyanamide. Ethanol failed to stimulate generation of chemotactic activity by either rat dermal fibroblasts, hepatic sinusoidal endothelial cells, or Kupffer cells. The chemotactic activity generated by ethanol-treated rat hepatocytes was recovered from culture supernatants in the lipid phase after extraction with chloroform/methanol. Thin-layer chromatography and high performance liquid chromatography of chloroform/methanol extracts demonstrated that the chemotactic factor probably is a polar lipid. This chemotactic lipid may account, in part, for the leukocytic infiltration of the liver parenchyma that is observed during the course of acute alcoholic hepatitis.
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PMID:Production of chemotactic activity for polymorphonuclear leukocytes by cultured rat hepatocytes exposed to ethanol. 643 93

Mutants of Escherichia coli resistant to allyl alcohol were selected. Such mutants were found to lack alcohol dehydrogenase. In addition, mutants with temperature-sensitive alcohol dehydrogenase activity were obtained. These mutations, designated adhE, are all located at the previously described adh regulatory locus. Most adhE mutants were also defective in acetaldehyde dehydrogenase activity.
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PMID:Escherichia coli mutants with a temperature-sensitive alcohol dehydrogenase. 675 27


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