Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

A liver protein with molecular weight of 37,000 can form adducts with acetaldehyde in vivo when rats are fed alcohol chronically. This 37KD protein is not directly involved in the hepatic metabolism of ethanol but it requires alcohol dehydrogenase activity to form adducts with acetaldehyde. The 37KD protein-AA is located in cytosol of the liver. However, under certain circumstances e.g. when fed an alcohol-containing liquid diet supplemented with cyanamide (an aldehyde dehydrogenase inhibitor that raises blood acetaldehyde concentrations), this 37KD protein-acetaldehyde adduct (protein-AA) becomes incorporated into liver plasma membranes. The same 37KD protein-AA can also form in vitro with cultured rat hepatocytes treated with ethanol. The formation of the 37KD protein-AA in the cultured liver cells increased with time and was dependent on concentrations of ethanol in the culture medium. Thus, protein-AAs can form in vivo and in liver cell culture upon chronic alcohol exposure, and a 37KD protein in liver is highly susceptible to chemical modification by acetaldehyde.
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PMID:Formation of the 37KD liver protein-acetaldehyde adduct in vivo and in vitro. 184 47

The effects of gossypol on ethanol-elicited responses pertaining to liver ethanol, acetaldehyde-metabolizing enzymes and alcohol preference were studied in rodents. Intraperitoneal injection of a single dose of gossypol, 100 mg/kg, inhibited hepatic alcohol dehydrogenase for 50 h in mice from both sexes. The acute gossypol treatment produced earlier inhibition of mouse liver cytoplasmic aldehyde dehydrogenase in male than female mice. Acute gossypol administration initially inhibited mouse liver subcellular mitochondrial aldehyde dehydrogenase in both sexes which was not evident 50 h later. Administration of gossypol, 10 mg/kg i.p., to male rats with preference for ethanol caused aversion for ethanol drinking. The enzymatic determinations indicate gender sensitivity of subcellular mouse liver aldehyde dehydrogenase to gossypol. The behavioral study suggests adverse metabolic interaction between gossypol and alcohol which may underlie the rat aversion to voluntary ethanol drinking.
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PMID:Behavioral and metabolic interaction between gossypol and ethanol. 185 62

Metadoxine (pyridoxine-pyrrolidone carboxylate) has been reported to accelerate ethanol metabolism. In the present work we have investigated the effect of metadoxine on the activities of isolated alcohol and aldehyde dehydrogenases from rat and man, and on the activity of these enzymes in chronic ethanol-fed rats. Our results indicate that in vitro metadoxine does not activate any of the enzymatic forms of alcohol dehydrogenase (classes I and II) or aldehyde dehydrogenase (low-Km and high-Km, cytosolic and mitochondrial). At concentrations higher than 0.1 mM, metadoxine inhibits rat class II alcohol dehydrogenase, although this would probably not affect the physiological ethanol metabolism. Chronic ethanol intake for 5 weeks results in a 25% decrease of rat hepatic alcohol dehydrogenase (class I) activity as compared with the pair-fed controls. The simultaneous treatment with metadoxine prevents activity loss, suggesting that the positive effect of metadoxine on ethanol metabolism can be explained by the maintenance of normal levels of alcohol dehydrogenase during chronic ethanol intake. No specific effect of chronic exposure to ethanol or to metadoxine was detected on rat aldehyde dehydrogenase activity.
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PMID:Action of metadoxine on isolated human and rat alcohol and aldehyde dehydrogenases. Effect on enzymes in chronic ethanol-fed rats. 187 Mar 55

Effect of ethanol administration on the severity of myocardial infarction induced by isoproterenol in rats was studied. Even though serum CPK and GOT levels as well as the extent of myocardial damage as revealed by histopathological studies, were similar, the survival rate was higher in rats administered ethanol. Concentration of cholesterol and triglycerides in the serum and heart in rats given ethanol and isoproterenol seems to be the additive effect caused individually by ethanol and isoproterenol. Myocardial alcohol dehydrogenase and aldehyde dehydrogenase both showed increased activity in rats treated with ethanol. The rate of recovery from myocardial infarction however, was slower in rats treated with ethanol as judged from the serum CPK value.
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PMID:Effect of ethanol administration on metabolism of lipids in heart and aorta in isoproterenol induced myocardial infarction in rats. 187 39

Alcohol (ethanol) use during pregnancy can produce a wide spectrum of effects in the developing embryo/fetus that are dependent on the maternal drinking pattern. The effects of chronic ethanol exposure on the developing conceptus are reviewed with primary focus on ethanol teratogenesis, manifesting in the human as the fetal alcohol syndrome or fetal alcohol effects. The effects of acute ethanol exposure on the near-term fetus are described, including suppressed fetal breathing movements, electrocorticographic (ECoG) activity and electrooculographic (EOG) activity. The ethanol-induced suppression of fetal breathing movements is a very sensitive index of acute exposure of the near-term fetus to ethanol, and appears to involve a direct mechanism of action rather than an indirect mechanism involving suppression of electrocortical activity. The disposition of ethanol and its pharmacologically active proximate metabolite, acetaldehyde, and the activity of alcohol dehydrogenase and aldehyde dehydrogenase in the near-term maternal-fetal unit are described, and a pharmacokinetic model is proposed. The effects of short-term ethanol exposure on the near-term fetus include the development of tolerance to the ethanol-induced suppression of fetal breathing movements, low-voltage ECoG activity and EOG activity. The development of tolerance occurs more rapidly to the latter two fetal biophysical activities. The mechanism of tolerance development appears to be pharmacodynamic (functional) in nature, as there is no increase in the rate of ethanol elimination from the maternal-fetal unit. The role of prostaglandins (PGs) in the mechanism of the ethanol-induced suppression of fetal breathing movements is described. In the near-term fetus, there is a direct relationship between fetal blood ethanol concentration and fetal plasma PGE2 concentration, and an inverse relationship between the incidence of fetal breathing movements and each of fetal plasma and fetal cerebrospinal fluid (CSF) PGE2 concentrations. Indomethacin, a PG synthetase inhibitor, selectively blocks and reverses the ethanol-induced suppression of fetal breathing movements. These data support the postulates that the ethanol-induced suppression of fetal breathing movements is mediated by increased PGE2 concentration in the near-term fetus and that the ability of indomethacin to antagonize the ethanol-induced suppression of fetal breathing movements is due to its biochemical action to decrease fetal PGE2 concentration.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Effects of alcohol (ethanol) on the fetus. 187 37

We used titration with the inhibitors tetramethylene sulphoxide and isobutyramide to assess quantitatively the importance of alcohol dehydrogenase in regulation of ethanol oxidation in rat hepatocytes. In hepatocytes isolated from starved rats the apparent Flux Control Coefficient (calculated assuming a single-substrate irreversible reaction with non-competitive inhibition) of alcohol dehydrogenase is 0.3-0.5. Adjustment of this coefficient to allow for alcohol dehydrogenase being a two-substrate reversible enzyme increases the value by 1.3-1.4-fold. The final value of the Flux Control Coefficient of 0.5-0.7 indicates that alcohol dehydrogenase is a major rate-determining enzyme, but that other factors also have a regulatory role. In hepatocytes from fed rats the Flux Control Coefficient for alcohol dehydrogenase decreases with increasing acetaldehyde concentration. This suggests that, as acetaldehyde concentrations rise, control of the pathway shifts from alcohol dehydrogenase to other enzymes, particularly aldehyde dehydrogenase. There is not a single rate-determining step for the ethanol metabolism pathway and control is shared among several steps.
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PMID:The importance of alcohol dehydrogenase in regulation of ethanol metabolism in rat liver cells. 189 55

In this study we have examined the roles of alcohol dehydrogenase, aldehyde oxidase, and aldehyde dehydrogenase in the adaptation of Drosophila melanogaster to alcohol environments. Fifteen strains were characterized for genetic variation at the above loci by protein electrophoresis. Levels of in vitro enzyme activity were also determined. The strains examined showed considerable variation in enzyme activity for all three gene-enzyme systems. Each enzyme was also characterized for coenzyme requirements, effect of inhibitors, subcellular location, and tissue specific expression. A subset of the strains was chosen to assess the physiological role of each gene-enzyme system in alcohol and aldehyde metabolism. These strains were characterized for both the ability to utilize alcohols and aldehydes as carbon sources as well as the capacity to detoxify such substrates. The results of the above analyses demonstrate the importance of both alcohol dehydrogenase and aldehyde dehydrogenase in the in vivo metabolism of alcohols and aldehydes.
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PMID:The involvement of alcohol dehydrogenase and aldehyde dehydrogenase in alcohol/aldehyde metabolism in Drosophila melanogaster. 190 6

Methylazoxymethanol (MAM) is the short-lived toxic and carcinogenic aglycone of cycasin, a natural component of the cycad plant. In the present study, the stable acetate ester of MAM, MAM acetate, was tested in combination with porcine liver esterase and Salmonella typhimurium His G46 to study the comparative mutagenicity of this compound in the presence of rat hepatic alcohol dehydrogenase (ADH), aldehyde dehydrogenase (ALDH), and rat liver microsomes. In the presence of rat liver microsomes and an NADPH-generating system, mutagenicity of MAM acetate was not significantly altered. However, addition of rat liver 105,000g supernatant fraction and/or NAD+ significantly increased the number of his+ revertants above control. A concentration-dependent increase in mutagenicity of MAM acetate was observed for NAD+ from 50 to 200 microM, while NADP+ caused a decrease in mutagenicity of MAM acetate in this same concentration range. Pyrazole (100-500 microM) had no significant effect on mutagenicity of MAM acetate in the presence of rat liver 105,000g supernatant, while disulfiram at 500 microM resulted in a significant decrease in mutagenicity of MAM acetate. The results of this study implicate ALDH as essential in activation of MAM acetate to a mutagenic species in this system, while the role of ADH and microsomes appears to be minimal.
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PMID:Mutagenicity of methylazoxymethanol acetate in the presence of alcohol dehydrogenase, aldehyde dehydrogenase, and rat liver microsomes in Salmonella typhimurium His G46. 191 9

1. Gossypol, an antifertility ingredient of the cotton plant, altered specific activity of mouse liver alcohol dehydrogenase (L-ADH) and subcellular aldehyde dehydrogenase (L-ALDH) in mice of both sexes. 2. Intraperitoneal injection of a single gossypol dose, 50 mg/kg, inhibited both male and female L-ADH and cytoplasmic L-ALDH from saline controls 21 hr after drug treatment. 3. Gossypol inhibited female but not male mouse mitochondrial L-ALDH isoenzymes. 4. Gossypol-produced enzyme inhibition was determined as noncompetitive. 5. The results suggest gender-dependent sensitivity of mitochondrial L-ALDH to the gossypol inhibition. A toxic metabolic interaction between ethanol and gossypol has been indicated which suggests the contraindication of alcoholic beverages during gossypol use.
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PMID:Effect of gossypol on kinetics of mouse liver alcohol and aldehyde dehydrogenase. 193 90

Little is known about factors determining individual susceptibility to the physical complications of alcohol abuse but genetically determined differences in ethanol metabolism may be important. The oxidative metabolism of alcohol is catalyzed by alcohol and aldehyde dehydrogenase. Polymorphisms have been observed at two of the five loci encoding alcohol dehydrogenase subunits: ADH2 (producing three beta subunits) and ADH3 (producing two tau subunits) and also at the locus encoding the metabolically important form of aldehyde dehydrogenase, ALDH2. We have compared ADH2, ADH3 and ALDH2 allele frequencies in patients with alcohol-related cirrhosis (n = 59) and chronic pancreatitis (n = 13) with 79 local healthy control subjects. The different alleles were detected with allele-specific oligonucleotide probes after amplification of leukocyte DNA by the polymerase chain reaction. All patients and all but one control subject were homozygous ADH2*1, encoding the beta 1 subunit. No ADH2*3 alleles were detected. All 34 patients and 39 control subjects tested were homozygous ALDH2*1 encoding the active enzyme. ADH3 allele frequencies were different in patients and control subjects. ADH3*1 frequency: control subjects, 55.1%; cirrhotic patients, 62.7%; chronic pancreatitis patients, 65.4%. The difference between the patient groups combined and the control subjects was significant (p less than 0.05; G-test of Sokal and Rohlf) if it was assumed that the allele frequency in our control population was a reasonable estimate of our local population allele frequency. These results suggest that genetically determined differences in alcohol metabolism may, in part, explain predisposition to alcohol-related end-organ damage.
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PMID:Investigation of the role of polymorphisms at the alcohol and aldehyde dehydrogenase loci in genetic predisposition to alcohol-related end-organ damage. 193 84


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