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)

The binding of NAD+, NADH, and ADP-ribose to horse liver alcohol dehydrogenase has been studied calorimetrically as a function of pH at 25 degrees C. The enthalpy of NADH binding is 0 +/- 0.5 kcal mol-1 in the pH range 6 to 8.6. The enthalpy of NAD+ binding, however, varies with pH in a sigmoidal fashion and is -4.0 kcal mol(NAD)-1 at pH 6.0 and +4.5 kcal mol(NAD)-1 at pH 8.6 with an apparent pKa of 7.6 +/- 0.2. The enthalpy of proton ionization of the group on the enzyme is calculated to be in the range 8.8 to 9.8 kcal mol(H+)-1. In conjunction with the available thermodynamic data on the ionization of zinc-bound water in model compounds, it is concluded that the group with a pKa of 9.8 in the free enzyme and 7.6 in the enzyme . NAD+ binary complex is, most likely, the zinc-bound water molecule. Our studies with zinc-free enzyme provide further evidence for this conclusion. Therefore, the processes involving a conformational change of the enzyme upon NAD+ binding and the suggested mechanism of subsequent quenching of the fluorescence of Trp-314 implicating the participation of an ionized tyrosine group must be re-evaluated in the light of this thermodynamic study.
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PMID:The enthalpy of protolysis of liver alcohol dehydrogenase upon binding nicotinamide adenine dinucleotide. 3 45

4-Methylpyrazole, in a dose producing inhibition of alcohol dehydrogenase (alcohol:NAD(+) oxidoreductase, EC 1.1.1.1), was given alone or together with ethanol (10%) as sole drinking fluid to growing rats for up to 38 weeks. Their weight curves remained normal. Electron microscopy of liver, kidney, and heart revealed no changes related to treatment. Hematologic analysis showed normal values for blood and bone marrow. Several clinical chemical parameters showed no impairment of liver or kidney function, except for an enhancement of the microsomal drug-metabolizing activity after concurrent administration of 4-methylpyrazole and ethanol. A study on rats receiving 4-methylpyrazole and ethanol indicated a mutual interaction of the two compounds or the metabolites, leading to increased concentration in the blood of the compounds and reduced formation of 4-hydroxymethylpyrazole, the primary metabolite of 4-methylpyrazole. In monkeys, elimination of 4-methylpyrazole followed a linear course. 4-Hydroxymethylpyrazole accumulated to a level of at most 10% of that of 4-methylpyrazole. Concurrent administration of methanol inhibited the elimination of 4-methylpyrazole about 25%, and 4-methylpyrazole produced a profound inhibition of the oxidation of methanol. 4-Methylpyrazole, at a level in the plasma of more than 10 muM, prevented accumulation of the toxic metabolite formic acid in methanol-poisoned monkeys, and repeated injections of 4-methylpyrazole abolished methanol toxicity in monkeys receiving lethal doses of methanol. The present investigation indicates that 4-methylpyrazole, with its low toxicity and strong inhibition of alcohol oxidation, is a valuable tool for experimental studies of alcohol metabolism and its effects. It illustrates the usefulness of the monkey as a model to study 4-methylpyrazole activity and toxicity in light of its possible use for treating methanol poisoning in human beings.
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PMID:Pyrazoles as inhibitors of alcohol oxidation and as important tools in alcohol research: an approach to therapy against methanol poisoning. 11 4

Activities of enzymes involved in fructose metabolism were measured in samples of human kidney cortex and medulla. The enzymes are ketohexokinase, aldolase, NAD- and NADP-dependent alcohol dehydrogenase, aldehyde dehydrogenase, triokinase and glycerate kinase; hexose biphosphatase and sorbitol dehydrogenase were also investigated. With the exception of glycerate kinase, all enzymes involved in fructose metabolism were found in the human cortex and medulla. The enzyme levels in the medulla were low in comparison with the cortex.
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PMID:Enzymes of fructose metabolism in human kidney. 16 31

Literature on the properties of liver alcohol dehydrogenase (ADH) from man, horse and rat is reviewed and discussed under two major headings: 1) physical and chemical properties of ADH and 2) structure-function relationship in isoenzymes. Under the first heading are discussed: molecular weight, subunit composition catalytic sites per molecule, sulfhydryl groups, end groups, amino acid composition, role of Zn++ in the structure and function, coenzyme specificity and binding, conformational changes, substrate specificity, catalytic mechanism and recent results from x-ray crystallography of horse liver ADH. The physicochemical properties of ADH from man, horse and rat are for the most part similar. All three enzymes have identical molecular weights, similar amino acid compositions, consist of two subunits, and are all metalloenzymes containing Zn++: horse and human ADH contain one coenzyme binding site per subunit; no results are available for the rat ADH. ADH catalyses interconversion of a large variety of saturated and unsaturated aliphatic and aromatic alcohols and the corresponding aldehydes and ketones utilizing NAD(H). The physiological role of ADH is uncertain. ADH readily combines with reduced coenzymes to form binary complexes with low dissociation constants (10-7 to 10-8M); in the ternary complexes with coenzymes and substrate-competitive inhibitors, these constants are even lower. In the presence of suitable inhibitors, the enzymes can be titrated by coenzymes employing fluorometric and spectrophotometric procedures. The rate of the overall reaction catalyzed by ADH is determined by the dissociation rates of coenzymes, the slowest steps in the reaction sequence. Under the second heading are discussed: liver ADH isoenzymes of horse, man, rat, rhesus monkey and other species, and the significance of steroid activity which accounts for the distinct substrate specificity of some isoenzymes. ADH from horse liver is a heterogeneous enzyme consisting of subunits of distinct substrate specificity and primary structure. The difference in the amino acid sequence between subunit E (active with classical ADH substrates, but not with steroids) and subunit S (active also with steroids) amounts to six amino acids out of 374. Human ADH is also heterogeneous, and at least five genes code for polypeptides which, by dimerization, form different isoenzymes. Experimental evidence suggests that rat ADH is a single unique protein which, like horse liver ADH, SS, is active with steroids. The physiological significance of steroid activity of ADHs is unknown. (Four tables with comparative data and one figure are presented).
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PMID:Mammalian liver alcohol dehydrogenases. 16 54

The addition of saturating concentrations of NAD-+ and alcohol to liver alcohol dehydrogenase in a stopped flow fluorimeter results in a triphasic quenching of enzyme fluorescence. A rapid quenching occurs with a rate constant of 300 to 500 s-minus 1, followed by a slower reaction at 50 to 100 s-minus 1, and ultimately followed by a very slow reaction. The addition of NAD-+ to enzyme in the absence of substrate causes a rapid quenching of enzyme fluorescence at 300 to 500 s-minus 1, with the same amplitude as the rapid phase in the presence of substrate. These studies demonstrate that NAD-+ binding to liver alcohol dehydrogenase causes a conformational change at a rate compatible with the previously reported rate constant for proton release, indicating that proton release is probably coupled to the conformational change.
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PMID:Quenching of protein fluorescence by transient intermediates in the liver alcohol dehydrogenase reaction. 16 2

Alcohol dehydrogenase from horse (isoenzyme SS and ES, but not EE), rat and human liver were found to catalyze the NAD-dependent oxidation of 3beta-hydroxy groups in 5alpha- and 5beta-steroids of the C19, C21, and C24 series. The enzymes from horse and rat liver were more active on 5beta-than on 5alpha-steroids. This difference was most marked with the enzyme from rat liver, especially with 3beta-hydroxyandrostan-17-ones and 3beta-hydroxypregnan-20-ones as substrates. The Km of isoenzyme ES from horse liver was lower for 3beta-hydroxy-5alpha-cholanoic acid (0.4 muM) than for 3beta-hydroxy-5beta-cholanoic acid (0.9 muM). 3alpha-Hydroxysteroids were not substrates for the enzymes from horse and rat liver. Human liver alcohol dehydrogenase had low affinity for 3beta-hydroxy-5alpha (and 5beta)-cholanoic acids, but oxidation could be clearly demonstrated by gas chromatographic analysis of the products.
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PMID:Steroid oxidoreductase activity of alcohol dehydrogenases from horse, rat, and human liver. 17 Jul 65

The fluorescence of the natural coenzyme, NADH, is used to monitor the environment of the nicotinamide moiety at the active centre of rabbit muscle glyceraldehyde-3-phosphate dehydrogenase (EC 1.2.1.12). Changes of the fluorescence quantum yield and polarization of a small amount of NADH, totally bound by an excess of enzyme, show that at half-saturation of the oligomer with NAD a conformational change is induced which affects the active centre regions of the remaining subunits. This conformational transition is not effected by adenosine diphosphoribose, suggesting that the binding of the nicotinamide moiety of NAD to two subunits is essential for the change of tertiary structure of the remaining subunits that causes the observed changes of the fluorescence properties of the ADH "tracer probe". It is suggested that this conformational transition of the oligomer is responsible for the major decrease of affinity for NAD which occurs at half-saturation, and possibly for the activation by NAD+ of the reductive dephosphorylation reaction catalysed by the enzyme. It is also suggested, by analogy with haemoglobin, that the molecular basis of the negative cooperativity may be the creation of additional intersubunit bonds during the binding of the first two NAD molecules to the tetramer, and a change from a "relaxed" quaternary structure to a "tense" structure at half-saturation.
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PMID:Conformational changes of glyceraldehyde-3-phosphate dehydrogenase induced by the binding of NAD. A unified model for positive and negative cooperativity. 17 91

In vitro experiments, using rat liver homogenates, were designed to examine certain of the proposed enzymatic mechanisms for the interaction of oral hypoglycemic drugs with monoamine and ethanol metabolism. The oxidative degradation of tryptamine was studied by measuring indoleacetic acid (IAA) production and conclusions were drawn with regard to the activity of monoamine oxidase, aldehyde dehydrogenase and ethanol dehydrogenase. Acetohexamide, hydroxyhexamide, tolazamide, tolbutamide and chlorpropamide failed to reveal any specific inhibition of the three enzymes. Ethanol (0.2% w/v) and disulfiram decreased IAA formation, as did a lack of available aldehyde dehydrogenase and NAD, but these reductions were not enhanced by the hypoglycemic agents. The results suggest that the 'disulfiram-like' reaction which occurs in certain patients imbibing ethanol while receiving oral hypoglycemic drugs, depends upon some factor(s) other than, or additional to, a specific interference with monoamine and/or ethanol metabolism.
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PMID:Studies on the biochemical aspects of the 'disulfiram-like' reaction induced by oral hypoglycemics. 17 18

Group N streptococci formed acetaldehyde and ethanol from glucose. As the enzymes aldehyde dehydrogenase, phosphotransacetylase and acetate kinase were present this would enable these organisms to reduce acetyl-CoA to acetaldehyde and convert acetyl-CoA to acetyl phosphate and acetate. A pentose phosphate pathway which converted ribose-5-phosphate to glyceraldehyde-3-phosphate was also present. Acetaldehyde could not be formed via the hexose monophosphate shunt or by direct decarboxylation of pyruvate, as the enzymes phosphoketolase and alpha-carboxylase were absent. Phosphoketolase activity was induced in Streptococcus lactis subsp. diacetylactis after growth on D-xylose. Group N streptococci also contained an NAD-dependent alcohol dehydrogenase which reduced acetaldehyde to ethanol while both NAD- and NADP-dependent alcohol dehydrogenase activities were found in Leuconostoc cremoris.
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PMID:Acetaldehyde: an intermediate in the formation of ethanol from glucose by lactic acid bacteria. 17 70

The potential of sand as a support for immobilized enzymes was investigated by preparing alkylamine sand and devising methods to measure the total number of amine groups present and the fraction available for immobilization of enzymes. Alcohol dehydrogenase (alcohol: NAD oxidoreductase, EC 1.1.1.1.) and lactate dehydrogenase (L-lactate:NAD oxidoreductase, EC 1.1.1.27) were immobilized on alkylamine sand, and the stability of the immobilized protein and dehydrogenase activity was measured. Urease (urea amidohydrolase, EC 3.5.1.5) was also immobilized on sand to test the applicability of these methods to larger scale immobilizations. Results suggest that sand shows promise as a support for immobilized enzymes.
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PMID:Characterization of sand as a support for immobilized enzymes. 17 87


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