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)

1. The various isozymes of human alcohol dehydrogenase have been examined by Blue Sepharose column chromatography. 2. The products (alpha, beta1 and gamma1) of the common alleles at the three ADH loci (ADH1 ADH2 and ADH3 respectively) were found to show slight, but significant differences in their affinities for Blue Sepharose. The order of affinity of the homodimeric isozymes was: alphaalpha less than gamma1gamma1 less than beta1beta1. The heterodimeric isozymes showed intermediate affinities. 3. The products (gamma1 and gamma2) of the common alleles (ADH31 and ADH32 respectively) at the ADH3 locus showed a pronounced difference in their affinities: the gamma1gamma1 isozyme was firmly adsorbed by Blue Sepharose, whereas the gamma2gamma2 isozyme was not adsorbed. The heterodimeric gamma1gamma2 isozyme was intermediate in its behaviour. 4. The 'usual' and 'atypical' forms of ADH were indistinguishable by Blue Sepharose column chromatography. 6. The 'anodal' form of ADH showed no affinity for Blue Sepharose.
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PMID:Blue Sepharose chromatography of human alcohol dehydrogenase: evidence for interlocus and interallelic differences in affinity characteristics. 65 29

Sulfoxides inhibit horse liver alcohol dehydrogenase (EqADH) by binding to the enzyme-NADH complex. X-ray crystallography suggests that sulfoxides make a cation-pi interaction with the benzene ring of Phe-93 [Cho et al. (1997) Biochemistry 36, 382-389]. Structure-function relationships were examined with seven different sulfoxides binding to five human enzymes (alpha, beta1, gamma2, pi, and sigma) and three mutated forms of the horse enzyme. The human gamma2 enzyme, EqADH, and EqADH with Phe-93 replaced with Trp were selectively and strongly inhibited (Ki </= 1 microM) by the 3-butyl or hexyl derivatives of thiolane 1-oxide. The other human enzymes (all with Thr-48) and EqADH with Ser-48 substituted with Thr had relatively lower affinities for the thiolane 1-oxides due to close contact of the methyl group of Thr-48 with a carbon adjacent to the sulfoxide sulfur. EqADH binds the S isomers of 3-butylthiolane 1-oxides, hexyl methyl sulfoxide, and phenyl methyl sulfoxide more tightly than the R isomers, but EqADH with Phe-93 substituted with Ala and the human alpha enzyme (with Ala-93) prefer (R)-phenyl methyl sulfoxide, apparently because the phenyl ring fits into the space near residue 93. EqADH and the enzymes with Phe-93 replaced with Ala or Trp had similar affinities for sulfoxides, indicating that the contribution of the cation-pi interaction to binding is small or compensated for by altered interactions. Ab initio calculations also suggest that the interaction of a sulfoxide with benzene is relatively weak.
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PMID:Specificity of alcohol dehydrogenases for sulfoxides. 952 68

Human alcohol dehydrogenase (HsADH) comprises class I (alpha, beta, and gamma), class II (pi), and class IV (sigma) enzymes. Selective inhibitors of the enzymes could be used to prevent the metabolism of alcohols that form toxic products. Formamides are unreactive analogues of aldehydes and bind to the enzyme-NADH complex [Ramaswamy, S.; Scholze, M.; Plapp, B. V. Biochemistry 1997, 36, 3522-3527]. They are uncompetitive inhibitors against varied concentrations of alcohol, and this makes them effective even with saturating concentrations of alcohols. Molecular modeling led to the design and synthesis of a series of cyclic, linear, and disubstituted formamides. Evaluation of 23 compounds provided structure-function information and selective inhibitors for the enzymes, which have overlapping but differing substrate specificities. Monosubstituted formamides are good inhibitors of class I and II enzymes, and disubstituted formamides are selective for the alpha enzyme. Selective inhibitors, with Ki values at pH 7 and 25 degrees C of 0.33-0.74 microM, include N-cyclopentyl-N-cyclobutylformamide for HsADH alpha, N-benzylformamide for HsADH beta1, N-1-methylheptylformamide for HsADH gamma2, and N-heptylformamide for HsADH sigma and HsADH beta1.
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PMID:Inhibition of human alcohol dehydrogenases by formamides. 957 95

Ethanol enhances mesolimbic/cortical dopamine activity in reward and reinforcement circuits. We investigated the hypothesis that risk for alcoholism may be mediated by genes for neurotransmitters associated with the dopamine reward system as well as genes for enzymes involved in ethanol metabolism. DNA was extracted from brain tissue collected at autopsy from pathologically characterized alcoholics and controls. PCR-based assays showed that alcoholism was associated with polymorphisms of the dopamine D2 receptor (DRD2) TaqI B (P = .029) and the GABAA-beta2 subunit C1412T (P = .012) genes, but not with the glutamate receptor subunit gene NMDAR2B (366C/G), the serotonin transporter gene (5HTTL-PR), the dopamine transporter gene DAT1(SLC6A3), the dopamine D2 receptor gene DRD2 TaqI A, or the GABAA alpha1(A15G), alpha6(T1519C), and gamma2(G3145A) subunit genes. The glial glutamate transporter gene EAAT2 polymorphism G603A was associated with alcoholic cirrhosis (P = .048). The genotype for the most active alcohol dehydrogenase enzyme ADH1C was associated with a lower risk of alcoholism (P = .026) and was less prevalent in alcoholics with DRD2TaqIA2/A2 (P = .047), GABAA-beta2 1412C/C (P = .01), or EAAT2 603G/A (P = .022) genotypes. Combined DRD2TaqI A or B with GABAA-beta2 or EAAT2 G603A genotypes may have a concerted influence in the predisposition to alcoholism.
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PMID:Association studies of neurotransmitter gene polymorphisms in alcoholic Caucasians. 1554 98

Alcohol dehydrogenase 1C (ADH1C or ADH3) genotype reportedly modifies the association between alcohol consumption and coronary heart disease (CHD) risk, as well as influencing plasma high-density lipoprotein (HDL) levels [Hines LM, Stampfer MJ, Ma J, et al. Genetic variation in alcohol dehydrogenase and the beneficial effect of moderate alcohol consumption on myocardial infarction. N Engl J Med 2001;344:549-55]. This relationship has been examined in a sample of middle-aged (50-61 years) men (total of 2773 with 220 CHD events), participating in the prospective Second Northwick Park Heart Study (NPHS II). Alcohol consumption was assessed by questionnaire as the number of units consumed in the previous week. Drinkers experienced lower CHD risk than abstainers [hazard ratio (HR) 0.73 (95% confidence intervals (CI) 0.53, 0.99; p=0.04)] and had significantly higher HDL and apolipoprotein (apo)AI concentrations (both p<0.0001) and a lower fibrinogen (p=0.02). Overall, there was no effect of ADHC1 gamma1>gamma2 genotype on plasma levels of HDL, apoAI or fibrinogen or on CHD risk. To consider whether the effect of alcohol consumption on risk was modulated by genotype, the men were divided into abstainers, modest drinkers (1-3 units/week) and those who consumed more than 3 units/week. Significant alcohol:genotype interaction on CHD risk was observed (p=0.02), with gamma2 homozygotes, who were modest drinkers, displaying 78% CHD risk reduction compared to gamma1 homozygotes (HR=0.22, 95% CI 0.05-0.94). There was, however, no association between genotype and apoAI, HDL or fibrinogen and this was not altered when alcohol intake was considered. These findings confirm that the cardiovascular benefit of modest alcohol consumption. ADH1C genotype modifies the relationship between alcohol consumption and CHD risk but at lower levels than previously reported.
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PMID:Genetic variation in alcohol dehydrogenase 1C and the beneficial effect of alcohol intake on coronary heart disease risk in the Second Northwick Park Heart Study. 1591 Aug 47