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)

Acetaldehyde and butyraldehyde are substrates for alcohol dehydrogenase in the production of ethanol and 1-butanol by solvent-producing clostridia. A coenzyme A (CoA)-acylating aldehyde dehydrogenase (ALDH), which also converts acyl-CoA to aldehyde and CoA, has been purified under anaerobic conditions from Clostridium beijerinckii NRRL B592. The ALDH showed a native molecular weight (Mr) of 100,000 and a subunit Mr of 55,000, suggesting that ALDH is dimeric. Purified ALDH contained no alcohol dehydrogenase activity. Activities measured with acetaldehyde and butyraldehyde as alternative substrates were copurified, indicating that the same ALDH can catalyze the formation of both aldehydes for ethanol and butanol production. Based on the Km and Vmax values for acetyl-CoA and butyryl-CoA, ALDH was more effective for the production of butyraldehyde than for acetaldehyde. ALDH could use either NAD(H) or NADP(H) as the coenzyme, but the Km for NAD(H) was much lower than that for NADP(H). Kinetic data suggest a ping-pong mechanism for the reaction. ALDH was more stable in Tris buffer than in phosphate buffer. The apparent optimum pH was between 6.5 and 7 for the forward reaction (the physiological direction; aldehyde forming), and it was 9.5 or higher for the reverse reaction (acyl-CoA forming). The ratio of NAD(H)/NADP(H)-linked activities increased with decreasing pH. ALDH was O2 sensitive, but it could be protected against O2 inactivation by dithiothreitol. The O2-inactivated enzyme could be reactivated by incubating the enzyme with CoA in the presence or absence of dithiothreitol prior to assay.
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PMID:Coenzyme A-acylating aldehyde dehydrogenase from Clostridium beijerinckii NRRL B592. 227 27

Vinyl acetate is subject to microbial degradation in the environment and by pure cultures. It was hydrolyzed by samples of soil, sludge, and sewage at rates of up to 6.38 and 1 mmol/h per g (dry weight) under aerobic and anaerobic conditions, respectively. Four yeasts and thirteen bacteria that feed aerobically on vinyl acetate were isolated. The pathway of vinyl acetate degradation was studied in bacterium V2. Vinyl acetate was degraded to acetate as follows: vinyl acetate + NAD(P)+----2 acetate + NAD(P)H + H+. The acetate was then converted to acetyl coenzyme A and oxidized through the tricarboxylic acid cycle and the glyoxylate bypass. The key enzyme of the pathway is vinyl acetate esterase, which hydrolyzed the ester to acetate and vinyl alcohol. The latter isomerized spontaneously to acetaldehyde and was then converted to acetate. The acetaldehyde was disproportionated into ethanol and acetate. The enzymes involved in the metabolism of vinyl acetate were studied in extracts. Vinyl acetate esterase (Km = 6.13 mM) was also active with indoxyl acetate (Km = 0.98 mM), providing the basis for a convenient spectrophotometric test. Substrates of aldehyde dehydrogenase were formaldehyde, acetaldehyde, propionaldehyde, and butyraldehyde. The enzyme was equally active with NAD+ or NADP+. Alcohol dehydrogenase was active with ethanol (Km = 0.24 mM), 1-propanol (Km = 0.34 mM), and 1-butanol (Km = 0.16 mM) and was linked to NAD+. The molecular sizes of aldehyde dehydrogenase and alcohol dehydrogenase were 145 and 215 kilodaltons, respectively.
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PMID:Degradation of vinyl acetate by soil, sewage, sludge, and the newly isolated aerobic bacterium V2. 228 14

The phosphorescence properties of liver alcohol dehydrogenase from horse were characterized at limiting concentrations of coenzyme and coenzyme analogues. The emission decay kinetics of Trp-314 in strong, slowly exchanging, ternary complexes with NADH/isobutyramide, NAD/pyrazole, and NADH/dimethyl sulfoxide displays a markedly nonexponential character. The analysis of decay components over the saturation curve reveals that the phosphorescence from singly bound protein molecules has a lifetime from 1 to 1.3 s, which is 2-3 times larger than observed with fully bound and unliganded enzyme. The remarkably tighter configuration reported by the triplet probe for the coenzyme-binding domain in half-saturated macromolecules is not exclusive of strongly inhibited ternary complexes. Measurements on binary complexes with NADH, ADPR, and the inactive coenzyme analogue 1,4,5,6-tetrahydronicotinamide adenine dinucleotide confirm that binding of the ligand to one subunit has qualitatively the same influence on protein structure. If the lifetime of Trp-314 provides clear evidence for an appreciable change in conformation at half-binding that is apparently triggered by the ADPR fragment of the coenzyme, such communication between subunits does not lead to allosteric phenomena in coenzyme binding.
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PMID:Room temperature phosphorescence of Trp-314 as a monitor of subunit communications in alcohol dehydrogenase from horse liver. 232 42

Human placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase was purified to homogeneity according to a five-step method, with chromatography on DEAE-Sepharose, Blue Sepharose, and Mono-Q FPLC as principal steps. Final yield was 23% and purification about 13,000-fold, with a specific activity of 24,000 milliunits/mg. The subunit molecular weight is about 29,000 as determined by sodium dodecyl sulfate/polyacrylamide gel electrophoresis, and the native protein molecular weight is about 54,000 as estimated by Sephadex G-100 chromatography, establishing the enzyme to be a dimer of similar-sized protein chains. The subunit N-terminal residue is methionine, and the alpha-amino group is free. The complete primary structure was determined by peptide analysis, based essentially on four different proteolytic treatments (Lys-specific protease, Glu-specific protease, Asp-specific protease, and CNBr). The protein chain is composed of 266 residues, with C-terminal glutamine. A microheterogeneity was detected at position 217, with both Cys and Tyr, in about equal amounts, from a preparation starting with a single placenta. No other subunit heterogeneities were detected. The protein is clearly but distantly related to insect alcohol dehydrogenases, characterized bacterial dehydrogenases of sugar metabolism, and bacterial and eukaryotic steroid dehydrogenases. Together, these results establish that placental 15-hydroxyprostaglandin dehydrogenase is a member of the short-chain nonmetalloenzyme alcohol dehydrogenase protein family. The protein has four cysteine residues (five with the positional microheterogeneity), but there is no evidence for functional importance of any of these residues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Purification and structural characterization of placental NAD(+)-linked 15-hydroxyprostaglandin dehydrogenase. The primary structure reveals the enzyme to belong to the short-chain alcohol dehydrogenase family. 233 93

Stereospecificities are reported for seven dehydrogenases from Acholeplasma laidlawii, an organism from an evolutionarily distinct branch of life which has not previously been studied from a stereochemical point of view. Three of the activities examined (alcohol dehydrogenase, lactate dehydrogenase, and alanine dehydrogenase) catalyze the transfer of the pro-R (A) hydrogen from NADH. Four other activities (3-hydroxy-3-methylglutaryl-CoA reductase, glyceraldehyde-3-phosphate dehydrogenase, glucose-6-phosphate dehydrogenase, and NADH oxidase) catalyze the transfer of the pro-S (B) hydrogen from NAD(P)H. The stereospecificity of hydroxymethylglutaryl-CoA reductase is notable because it is the opposite of that of hydroxymethylglutaryl-CoA reductases from yeast and rat. These data are used to derive the simplest historical model capable of explaining available experimental facts.
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PMID:The stereospecificities of seven dehydrogenases from Acholeplasma laidlawii. The simplest historical model that explains dehydrogenase stereospecificity. 236 93

Addition of ethanol and some other primary alcohols, except methanol, to cells and protoplasts (but not membrane particles) considerably stimulated the rate of oxygen consumption. This additional respiration was strongly inhibited by 0.1 mM KCN. The cyanide inhibition curve of endogenous substrate oxidation was slightly biphasic while in the presence of ethanol it became clearly biphasic having Ki values of approx. 0.1 and 0.5 mM. Based on the steady-state cytochrome spectra in the presence of 0.1 mM KCN, we attributed the lower Ki to cytochrome a602. Proteolysis of protoplasts external membrane proteins did not change the rate of endogeneous substrate oxidation but prevented the inhibition of this respiration by low concentrations of KCN and stimulation of oxygen consumption by ethanol. The activity of NAD(+)-dependent ethanol dehydrogenase in the cytoplasm was found to be 520 nmol NADH- x min-1 x mg-1 protein. Proteolysis of external membrane proteins apparently inhibits the operation of the cytochrome a602-containing electron transport branch inducing the suppression of electron flow from NADH to oxygen.
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PMID:Branched respiratory chain in aerobically grown Staphylococcus aureus--oxidation of ethanol by cells and protoplasts. 236 63

Exposure of early third instar larvae of Drosophila melanogaster to a nonlethal dose of ethanol was detrimental to larvae lacking alcohol dehydrogenase (ADH) but beneficial to wild-type larvae in terms of surviving a later ethanol tolerance test, indicating that one of the important functions of the ADH system is to supply derivatives of ethanol to larvae that in turn promote ethanol tolerance. High intracellular concentrations of ethanol in ADH-deficient (Adhn2) larvae fed ethanol were accompanied by a decrease in the cell membrane infoldings of fat body cells, suggesting that the capacities to absorb and release molecules were reduced. Marked effects of ethanol on the endoplasmic reticulum and mitochondria of ADH-deficient larvae were also evident. The absence of similar changes in wild-type larvae that were fed moderate levels of ethanol showed that the ADH system kept the intracellular level of ethanol at a concentration low enough to avoid cell damage. A cytometric analysis of electron micrographs showed that there were ethanol-induced reductions in glycogen, lipid, and protein stores in the fat body cells of ADH-deficient larvae fed 1.25% ethanol (v/v) compared with null larvae fed an ethanol-free diet. This finding implied that the capacities to synthesize or store these compounds may be limited by high intracellular concentrations of ethanol. The cytometric analysis also revealed that the consumption of diets containing 2.5% and 4.5% ethanol by Canton-S wild-type larvae for 3 days after 4 days of feeding on an ethanol-free diet resulted in decreases in glycogen and protein deposits in fat body cells, but increased the amount of lipid deposits compared to larvae fed an ethanol-free diet. This observation, coupled with the greater weight of wild-type adults that were fed a growth-limiting concentration of ethanol compared with control adults, suggested that a metabolic defense mechanism in larvae is to convert toxic ethanol to nontoxic storage products. Dietary ethanol alone and in combination with isopropanol stimulated an increase in the size of the NAD-pool in larvae, a condition that may favor the activity of ADH. A low dietary level of isopropanol (1%) completely blocked glycogen deposition in wild-type larvae, whereas ethanol did not. Thus ethanol and isopropanol exert some different toxic effects on larval fat bodies.
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PMID:Alcohol dehydrogenase and ethanol tolerance at the cellular level in Drosophila melanogaster. 249 60

Alcohol dehydrogenase (Adh) (alcohol:NAD+ oxidoreductase, EC 1.1.1.1) gene frequencies and ethanol tolerance in Drosophila melanogaster are known to exhibit long-range latitudinal variations on different continents; this has led to the argument that the clines are adaptive. Accordingly, tropical populations are characterized both by a low frequency of Adh-F and by a low ethanol tolerance. In the urban area of Brazzaville (Congo) under an equatorial African climate, an original genetic structure of local populations has been found: Adh-F frequency varies from 3% to 90% when countryside and brewery populations are compared. This variation is accompanied by an increase of ethanol tolerance (from 6% to 13% alcohol). Such differences, which have remained stable for the past 3 years, were observed between collection sites less than 1 km apart. Two other enzyme loci exhibited a correlated variation with Adh-F--i.e., an increase of the S allele of glycerol-3-phosphate dehydrogenase (NAD+) (sn-glycerol-3-phosphate:NAD+ 2-oxidoreductase, EC 1.1.1.8) and of the F allele of glucose-6-phosphate dehydrogenase (D-glucose-6-phosphate:NADP+ 1-oxidoreductase, EC 1.1.1.49). Such observations suggest very strong selective pressures exerted by environmental ethanol that oppose the gene flow due to adult dispersal between contiguous habitats. A functional relationship between the polymorphisms of the three enzyme loci seems likely, and a metabolic interaction involving NAD and NADP cofactors is proposed.
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PMID:Short-range genetic structure of Drosophila melanogaster populations in an Afrotropical urban area and its significance. 251 Jan 64

Analogues of oxidized nicotinamide adenine dinucleotide (NAD+) in which a 2,3-dihydroxycyclopentane ring replaces the beta-D-ribonucleotide ring of the nicotinamide riboside moiety of NAD+ have recently been synthesized [Slama, J. T., & Simmons, A. M. (1988) Biochemistry 27, 183]. Carbocyclic NAD+ analogues have been shown to inhibit NAD glycohydrolases and ADP-ribosyl transferases such as cholera toxin A subunit. In this study, the diastereomeric mixture of dinucleotides was separated, and the inhibitory capacity of each of the purified diastereomers was defined. The NAD+ analogue in which the D-dihydroxycyclopentane is substituted for the D-ribose is designated carba-NAD and was demonstrated to be a poor inhibitor of the Bungarus fasciatus venom NAD glycohydrolase. The diastereomeric dinucleotide pseudo-carbocyclic-NAD (psi-carba-NAD), containing L-dihydroxycyclopentane in place of the D-ribose of NAD+, was shown, however, to be a potent competitive inhibitor of the venom NAD glycohydrolase with an inhibitor dissociation constant (Ki) of 35 microM. This was surprising since psi-carba-NAD contains the carbocyclic analogue of the unnatural L-ribotide and was therefore expected to be a biologically inactive diastereomer. psi-Carba-NAD also competitively inhibited the insoluble brain NAD glycohydrolase from cow (Ki = 6.7 microM) and sheep (Ki = 31 microM) enzyme against which carba-NAD is ineffective. Sensitivity to psi-carba-NAD was found to parallel sensitivity to inhibition by isonicotinic acid hydrazide, another NADase inhibitor. psi-Carba-NAD is neither a substrate for nor an inhibitor of alcohol dehydrogenase, whereas carba-NAD is an efficient dehydrogenase substrate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Inhibition of NAD glycohydrolase and ADP-ribosyl transferases by carbocyclic analogues of oxidized nicotinamide adenine dinucleotide. 253 31

In a previous study of the metabolism of methyl-n-amylnitrosamine (MNAN) in the rat, 2- to 5-hydroxy-MNAN (HO-MNAN) were provisionally identified as metabolites and the identity of 4-HO-MNAN was confirmed by mass spectrometry. We now describe syntheses and mass and other spectra for 2- to 5-oxo-MNAN. Two previously unidentified MNAN metabolites were shown to be 3- and 4-oxo-MNAN. In addition to 4-HO-MNAN, we confirmed 3-HO-, 4-oxo- and (less certainly) 2-HO-MNAN as urinary MNAN metabolites by GLC-MS of HPLC fractions. Analysis with and without beta-glucuronidase treatment showed that the urinary HO-MNANs occurred as their beta-glucuronides. MNAN (25 mg/kg injected i.p.) had a blood half-life of 21 min in adult male rats. The blood also contained 4-HO- and 4-oxo-MNAN, which showed maximum levels that were 13 and 26% respectively of that for MNAN, and were cleared more slowly than MNAN. On incubation for 3 h with MNAN, rat esophagus produced 3- and 4-oxo-MNAN in yields that were 5% of those for the corresponding HO-MNANs. For MNAN metabolism, the 4-oxo-/4-HO-MNAN ratio of metabolites was 5% for adult rat liver and was 22% for adult hamster liver and 9-day-old rat liver. On incubation with 4-HO-MNAN for 3 h, oxidation to 4-oxo-MNAN was 16-25% for adult hamster or 9-day-old rat liver slices and for adult hamster liver homogenate. Homogenate activity was concentrated in the microsomal fraction, for which NAD was a more effective co-factor than NADP. A bacterial alcohol dehydrogenase oxidized 4-HO- to 4-oxo-MNAN in 38% yield/3 h. None of these preparations oxidized 2-HO- to 2-oxo-MNAN. It was concluded that 3- and 4-oxo-MNAN were metabolites of MNAN, apparently (for 4-oxo-MNAN) via HO-MNAN oxidation by a microsomal NAD-dependent enzyme, that 4-HO- and 4-oxo-MNAN formation was a major route of MNAN metabolism, and that 4-oxo-MNAN might play a role in MNAN carcinogenesis.
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PMID:Ketonitrosamines as metabolites of methyl-n-amylnitrosamine (MNAN) and its hydroxy derivatives in the rat. 259 Oct 9


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