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)

Rapid and sensitive micromethods for the study of alcohol dehydrogenase and adehyde dehydrogenase isozymes in skin extracts, cultured fibroblasts and other organs are presented. Possibilities for the application of these techniques to the study of interindividual variations in response to alcohol are discussed. While fibroblasts cultured from a skin biopsy from one Japanese individual revealed a heterodimer (ADH2 2-1) of alcohol dehydrogenase, skin extract from another Japanese showed a homodimer (ADH2 2-2). Up to four isozyme sets for aldehyde dehydrogenase (ALDH) were detected in various human organs and at least three sets were found in skin and fibroblasts extracts. Our preliminary data on liver, stomach, and skin indicate that ALDH is polymorphic and several loci are concerned in the determination of these isozyme sets.
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PMID:Alcohol metabolizing enzymes: studies of isozymes in human biopsies and cultured fibroblasts. 47 12

Pearl millet (Pennisetum typhoides) produces three ADH isozymes, sets I, II, and III, with set III being expressed only in anaerobically treated seeds of seedlings. Variant strains have been identified which produce ADH isozymes with altered electrophoretic mobilities for sets I and II but not for set III activity. Based on genetic analysis of these variants and on dissociation-reassociation experiments, we propose that the three ADH isozymes are dimers of subunits coded by two structural genes, Adh1 and Adh2, with set I being a homodimer specified by Adh1, set III a homodimer specified by Adh2, and set II a heterodimer formed between the products of Adh1 and Adh2.
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PMID:Genetic analysis of alcohol dehydrogenase isozymes in pearl millet (Pennisetum typhoides). 51 37

Two unlinked genes, Adh1 and Adh2, control of the production of alcohol dehydrogenase (ADH) in seeds of the animal sunflower (Helianthus annuus). Each gene is polymorphic, having F and S alleles. Starch gel electrophoretic zymograms of the four possible double homozygotes have three bands, representing two homodimers and an intermediately migrating intergenic isozyme. Zymograms of double heterozygotes consist of nine bands produced by ten isozymes: six intragenics and four intergenics, two of which are coincident. Results of dissociation-recombination (D-R) experiments are reported which demonstrate the subunit composition of the intergenic isozymes, thus supporting the relationships suggested by genetic studies. Densitometric tracings of the zymogram of a cleared gel and measurements of activities of homodimer isozymes eluted from gels follwoing D-R of an intergenic isozyme showed that the Adh2 isozymes were more that twice as active as those of Adh1. Measurements of activities of crude extracts from the four possible double homozygous genotypes indicated that the seeds of the genotype Adh1F/Adh2F, Adh2S/Adh2S produced more activity than the other three. This genotype is the most common one found in wild and cultivated stocks. Isozymes eluted following electrophoresis of the same extracts had averages of 19%, 70%, and 11% of total activity contributed by the Adh1, Adh2, and intergeneic isozymes, respectively. A simple but efficient method of isozyme elution from starch gels is described which resulted in nearly full expected recovery (approximately 46%) of the ADH activity in the applied sample.
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PMID:Dissociation-recombination of intergenic sunflower alcohol dehydrogenase isozymes and relative isozyme activities. 125 7

Biochemical analysis of a number of related unstable Drosophila melanogaster strains was carried out. These strains have been shown to undergo mutational transformations caused by insertion/excision of transposable elements (Gerasimova, 1985). Activity and mobility variants of alpha-GPDH, ADH, SOD, G6PD, 6PGD and EST-6 were analysed. Two loci controlling SOD and 6PGD proved to be invariable, the loci alpha-Gpdh and Est-6 causing reduced activity of their products in the initial strain ctMR2. The direct and reversed transformations analogous to the mutational passages of morphological characters were traced in two loci controlling ADH and G6PD. The data obtained are discussed in terms of up-to-date views on the functional role of transposable elements, in relation to the genetic stability of the strains studied, under the multiple transpositions of mobile elements.
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PMID:[Mutational variability of enzyme loci in unstable Drosophila melanogaster strains]. 211 91

The interaction of NADPH with ferric complexes to catalyze microsomal generation of reactive oxygen intermediates has been well studied. Experiments were carried out to characterize the ability of NADH to interact with various ferric chelates to promote microsomal lipid peroxidation and generation of .OH-like species. In the presence of NADH and iron, microsomes produced .OH as assessed by the oxidation of a variety of .OH scavenging agents. Rates of NADH-dependent .OH production were 50 to 80% those of the NADPH-catalyzed reaction. The oxidation of dimethyl sulfoxide or t-butyl alcohol was inhibited by catalase and competitive .OH scavengers but not by superoxide dismutase or carbon monoxide. NADH-dependent .OH production was effectively catalyzed by ferric-EDTA and ferric-diethylenetriaminepentaacetic acid (DTPA), whereas ferric-ATP and ferric-citrate were poor catalysts. All these ferric chelates were reduced by microsomes in the presence of NADH (and NADPH). H2O2 was produced in the presence of NADH in a reaction stimulated by the addition of ferric-EDTA, consistent with the increase in .OH production. The latter appeared to be limited by the rate of H2O2 generation rather than the rate of reduction of the ferric chelate. NADH-dependent lipid peroxidation was much lower than the NADPH-catalyzed reaction and showed an opposite response to catalysis by ferric complexes compared to .OH generation as production of thiobarbituric acid-reactive material was increased with ferric-ATP and -citrate, but not with ferric-EDTA or- DTPA, and was not affected by catalase, SOD, or .OH scavengers. These results indicate that NADH can support microsomal reduction of ferric chelates, with the subsequent production of .OH-like species and peroxidation of lipids. The pattern of response of the NADH-dependent reactions with respect to catalytic effectiveness of ferric chelates and sensitivity to radical scavengers is similar to that found with NADPH. Many of the metabolic actions of ethanol have been ascribed to production of NADH as a consequence of oxidation by alcohol dehydrogenase. Since the cytosol normally maintains a highly oxidized NAD+/NADH redox ratio, it is interesting to speculate that increased availability of NADH from the oxidation of ethanol may support microsomal reduction of iron complexes, with the subsequent generation of reactive oxygen intermediates.
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PMID:NADH-dependent microsomal interaction with ferric complexes and production of reactive oxygen intermediates. 255 68

Livers of rabbits contain three classes of alcohol dehydrogenase (ADH) isozymes which are highly analogous to the human classes. Class I ADHs migrate toward cathode on starch gel and are very sensitive to 4-methylpyrazole (4-MePz) inhibition. Class II ADH migrates slowly toward anode and is less sensitive to 4-MePz. Class III ADH migrates rapidly toward anode and is insensitive to 4-MePz. There are one class II, one class III and at least three class I ADH isozymes present in the rabbit liver. The three class I isozymes purified to homogeneity are all dimers with subunit molecular weight of 41700. Two are heterodimers composed of A-, C-chains and B-, C-chains, respectively. The third one is a homodimer, contains only the C-chain. These results indicate that among all the mammals examined, rabbit ADH bears the greatest resemblance to the human enzyme.
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PMID:Rabbit liver alcohol dehydrogenase: isolation and characterization of class I isozymes. 291 92

Three alcohol dehydrogenase (ADH) isozymes from embryos of the durum wheat cultivar Bijaga Yellow having the variant Adh-Alb allele were purified using (NH4)2SO4 precipitation, gel filtration, and ion-exchange chromatography. ADH is a dimeric enzyme. The variant isozyme ADH-1-1, which is a homodimer composed of alpha b monomers, was compared with ADH-1-5 (homodimer composed of beta a monomers), the product of Adh-B1, and the ADH-1-3 isozyme (alpha b beta a heterodimer) on a number of parameters including Km, substrate specificities, and molecular weights. No appreciable differences among the three isozymes were found, except for the faster electrophoretic mobility of alpha b alpha b dimers (ADH-1-1). The results indicate that the variant isozyme is the result of a mutation altering only the charge of the isozyme.
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PMID:Purification and characterization of variant alcohol dehydrogenase isozymes from durum wheat. 344 91

Class I isoenzymes of alcohol dehydrogenase (ADH) were isolated by chromatography of human liver homogenates on DEAE-cellulose, 4-[3-[N-(6-aminocaproyl)-amino]propyl]pyrazole--Sepharose and CM-cellulose. Eight isoenzymes of different subunit composition (alpha gamma 2, gamma 2 gamma 2, alpha gamma 1, alpha beta 1, beta 1 gamma 2, gamma 1 gamma 1, beta 1 gamma 1, and beta 1 beta 1) were purified, and their activities were measured at pH 10.0 by using ethanol, ethylene glycol, methanol, benzyl alcohol, octanol, cyclohexanol, and 16-hydroxyhexadecanoic acid as substrates. Values of Km and kcat for all the isoenzymes, except beta 1 beta 1-ADH, were similar for the oxidation of ethanol but varied markedly for other alcohols. The kcat values for beta 1 beta 1-ADH were invariant (approximately 10 min-1) and much lower (5-15-fold) than those for any other class I isoenzyme studied. Km values for methanol and ethylene glycol were from 5- to 100-fold greater than those for ethanol, depending on the isoenzyme, while those for benzyl alcohol, octanol, and 16-hydroxyhexadecanoic acid were usually 100-1000-fold lower than those for ethanol. The homodimer beta 1 beta 1 had the lowest kcat/Km value for all alcohols studied except methanol and ethylene glycol; kcat values were relatively constant for all isoenzymes acting on all alcohols, and, hence, specificity was manifested principally in the value of Km. Values of Km and kcat/Km revealed for all enzymes examined that the short chain alcohols are the poorest while alcohols with bulky substituents are much better substrates. The experimental values of the kinetic parameters for heterodimers deviate from the calculated average of those of their parent homodimers and, hence, cannot be predicted from the behavior of the latter. Thus, the specificities of both the hetero- and homodimeric isoenzymes of ADH toward a given substrate are characteristics of each. Ethanol proved to be one of the "poorest" substrates examined for all class I isoenzymes which are the predominant forms of the human enzyme. On the basis of kinetic criteria, none of the isoenzymes of class I studied oxidized ethanol in a manner that would indicate an enzymatic preference for that alcohol.
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PMID:Kinetic properties of human liver alcohol dehydrogenase: oxidation of alcohols by class I isoenzymes. 634 69

New molecular forms of human liver alcohol dehydrogenase (ADH), collectively designed ADH Indianapolis (ADHInd), were recently discovered in 29% of liver specimens from Black Americans [Bosron, W. F., Li, T.-K., and Vallee, B. L. (1981). Proc. Natl. Acad.Sci. USA 77:5784]. Three different ADHInd phenotypes have now been identified by starch gel electrophoresis, and four ADHInd enzyme forms isolated by affinity and ion-exchange chromatography. The most cathodic ADHInd form has a single pH optimum at 7.0 for ethanol oxidation and is a homodimer of a newly discovered subunit, as evidenced by dissociation--recombination studies. The remaining three purified ADHInd forms have dual pH optima for ethanol oxidation at 7.0 and 10.0 and generate two new bands on starch gel electrophoresis after dissociation-recombination. They appear to be heterodimers of this new subunit with the known subunits, alpha, beta 1, and gamma 1. Based on the occurrence of these four ADHInd isozymes and isozymes containing beta 1 subunits in the homogenate supernatants of 135 livers, we conclude that ADHInd results from polymorphism at the ADH2 locus, with the variant ADH2Ind allele coding for the beta Ind subunit. The frequency of ADH2Ind was 0.16 in Black Americans. The frequency of the ADH31 and ADH32 alleles also differed in these two populations.
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PMID:Human liver alcohol dehydrogenase: ADH Indianapolis results from genetic polymorphism at the ADH2 gene locus. 635 75

The electrophoretic pattern of alcohol dehydrogenase (ADH) of Drosophila mojavensis is composed of multiple bands. In previous studies from this laboratory we suggested on the basis of genetic evidence that multiple ADH bands were due to the presence of a gene duplication. In the studies presented here, this hypothesis is supported by data derived from comparing the protein biochemistry of each ADH. Three forms of D. mojavensis ADH have been isolated. These are the ADH-1 homodimer, the ADH-2 homodimer, and the ADH-1 ADH-2 interlocus heterodimer. Each of these isozymes has a native molecular weight of approximately 50,000. Each native molecule is composed of two subunits of identical size, 24,000 daltons. The native molecules differ slightly in their isoelectric points. Thermal denaturation also reveals that ADH-1 and ADH-2 are slightly different, ADH-1 being somewhat more thermostable. The interlocus heterodimer has properties intermediate between those of ADH-1 and those of ADH-2. Kinetic comparison also indicates a similarity among the three isozymes. ADH-2 is somewhat better at oxidizing ethanol relative to 2-propanol as compared to ADH-1. All of our studies support the general conclusion that the isozymes of ADH found in D. mojavensis are similar to one another and to other ADH from other species of Drosophila. This supports our hypothesis that multiple bands of ADH in D. mojavensis reflect the presence of a duplication of the Adh locus in that species.
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PMID:Biochemical characterization of the products of the Adh loci of Drosophila mojavensis. 636 55


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