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)

Oral administration of ethanol to rats at a dose of 3 g/kg decreased alcohol dehydrogenase (ADH) activity and metabolism of lactate to pyruvate in the liver. The effects of water extracts of Aloe and some other herbs on blood ethanol concentration and on ADH activity in liver cytosol were examined. The water extracts of these herbs caused a faster elimination of ethanol from blood of normal rats when administered orally 30 min before oral administration of ethanol. The rapid elimination of ethanol seems to be due to a protection of ADH activity and the supply of nicotinamide dinucleotide, both of which are reduced by high ethanol concentration. The effects of ethanol in decreasing the enzyme activities relating to its own metabolism occur when high concentrations of ethanol pass through the liver, and thus may primarily appear during the absorption of alcohol from the gastrointestinal tract, when portal concentration of ethanol are very high.
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PMID:Effect of water extracts of aloe and some herbs in decreasing blood ethanol concentration in rats. II. 272 Aug 44

A simple chemical method for introducing biotin into nucleic acids has been developed for the synthesis of nonisotopic hybridization probes. The method is based on the reaction of biotin hydrazide with amino residues of nucleic acids by using glutaraldehyde as a bifunctional coupling reagent. Biotin-labelled deoxyribonucleic acid (DNA) was detected by the use of alkaline phosphatase-labelled avidin, and alkaline phosphatase activity was measured by colorimetric and chemiluminescence methods. The chemiluminescence method using the nicotinamide adenine dinucleotide phosphate (NADP)/alcohol/alcohol dehydrogenase/microperoxidase/isoluminol system gave the highest sensitivity. A few picograms of lambda-phage DNA coated on a microtiter plate well could be detected by this method.
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PMID:Highly sensitive biotin-labelled hybridization probe. 280 62

The dinucleotide carbanicotinamide adenine dinucleotide (carba-NAD), in which a 2,3-dihydroxycyclopentane ring replaces the beta-D-ribonucleotide ring of the nicotinamide ribonucleoside moiety of NAD, has been synthesized and characterized enzymologically. The synthesis begins with the known 1-aminoribose analogue (+/-)-4 beta-amino-2 alpha,3 alpha-dihydroxy-1 beta-cyclopentanemethanol. The pyridinium ring is first introduced and the resultant nucleoside analogue specifically 5'-phosphorylated. Coupling the racemic carbanicotinamide 5'-mononucleotide with adenosine 5'-monophosphate produces two diastereomeric carba-NAD analogues which are chromatographically separable. Only one diastereomer is a substrate for alcohol dehydrogenase and on this basis is assigned a configuration analogous to D-ribose. The reduced dinucleotide carba-NADH was characterized by fluorescence spectroscopy and found to adopt a "stacked" conformation similar to that of NADH. The analogue is reduced by both yeast and horse liver alcohol dehydrogenase with Km and Vmax values for the analogue close to those observed for NAD. Carba-NAD is resistant to cleavage by NAD glycohydrolase, and the analogue has been demonstrated to noncovalently inhibit the soluble NAD glycohydrolase from Bungarus fasciatus venom at low concentrations (less than or equal to 100 microM).
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PMID:Carbanicotinamide adenine dinucleotide: synthesis and enzymological properties of a carbocyclic analogue of oxidized nicotinamide adenine dinucleotide. 283 53

The stereospecificity of IMP dehydrogenase (IMP:NAD+ oxidoreductase, EC 1.1.1.205) from two different sources was determined. The enzyme preparations were obtained from murine lymphoblasts and from Escherichia coli. Both enzymes transferred the 2-3H of IMP to the pro-S position of carbon atom C-4 of the nicotinamide ring in NAD. Thus, B-sided stereospecificity is common to the enzyme from two very different species. In addition, the studies described here demonstrate that alcohol dehydrogenase and NADH peroxidase, used as auxiliary enzymes, in combination with a microdistillation procedure, should permit rapid determination of the stereospecificity of any NAD-dependent dehydrogenase for which the appropriate tritiated substrate is available.
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PMID:A simple method for the rapid determination of the stereospecificity of NAD-dependent dehydrogenases applied to mammalian IMP dehydrogenase and bacterial NADH peroxidase. 288 73

N6-(N-[(4-Azido-3,5,6-trifluoro)pyridin-2-yl]-2-aminoethyl)- adenosine 5'-monophosphate has been synthesized and evidence presented for its structural assignment by ultraviolet and 19F-NMR spectroscopies. Its photolysis was shown to occur within 5 min. This AMP derivative behaves as a competitive inhibitor of NAD+ in horse-liver-alcohol-dehydrogenase-promoted oxidation of ethanol, with a Ki (0.95 mM) comparable to the Ki of AMP (1.9 mM). Moreover it is an activator of the enzyme when nicotinamide ribose is used as the oxidation cofactor. This activation is as good as that promoted by AMP or by the well known 8-azido-AMP. Upon photolysis of this new derivative in the presence of horse liver alcohol dehydrogenase, a covalent enzyme--analogue complex was isolated and assayed as a catalyst in the oxidation of ethanol using nicotinamide ribose as the cofactor. The reaction took place without complementation of AMP, indicating clearly that the AMP analogue is mainly covalently bound in the AMP-binding site, and that the linkage formed between the enzyme and the azido derivative has not dramatically altered the active site of the enzyme. A similar experiment with 8-azido-AMP produced a completely inactive complex.
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PMID:Synthesis and biological activity of N6-(N[(4-azido-3,5,6-trifluoro)-pyridin-2-yl]-2-aminoethyl)-adenosine 5'-monophosphate, a new AMP photoactivatable derivative. Covalent modification of horse liver alcohol dehydrogenase. 291 73

The structure of the complex between Cys-46-carboxymethylated horse liver alcohol dehydrogenase (CM-LADH) and reduced nicotinamide adenine dinucleotide (NADH) has been determined by X-ray analysis. The complex represents NADH binding to the orthorhombic, "open" conformation of the enzyme. Coenzyme binding here induces a local structural change in the peptide loop 293-297, but there is no domain rotation, as observed for the "closed" conformation of the protein. This local movement of a few residues in the loop is sufficient to trap the nicotinamide ring of NADH within the active-site area close to a productive binding position. The carboxymethyl group on the zinc ligand cysteine-46 is oriented between the pyrophosphate bridge of NADH and the guanidinium group of arginine-369 and can occupy this position because the coenzyme binding cleft remains open and unchanged upon coenzyme binding. The zinc coordination sphere is distorted, and the position of the metal atom is shifted 1 A compared to native unliganded LADH. The distance between the zinc ion and the sulfur of the alkylated cysteine residue is of the order of 3 A. Alkylation experiments were performed at 0.15 and 10 mM iodoacetate, and peptide maps were examined. Gentle treatment with reagent yields an enzyme product which is substituted at only one of the two zinc binding sites per subunit of LADH (Cys-46). This enzyme species maintains its structural integrity; it binds coenzyme which induces conformational changes resolved into two steps. Thus, in addition to the orthorhombic complex, a crystalline NADH complex in the closed conformation of CM-LADH was obtained. These crystals showed enzymic activity, and single crystals were analyzed with microspectrophotometric methods. Formation of the stable crystalline abortive complex between CM-LADH-NAD+ and 4-trans-(N,N-dimethylamino)cinnamaldehyde (DACA) could be observed upon addition of excess aldehyde to the closed complex of CM-LADH-NADH. The CM-LADH-NAD+-DACA complex is characterized by an intense absorption band with a lambda max at 456 nm which corresponds to a shift in the spectrum of free DACA of approximately 60 nm. At the higher concentration of iodoacetate, three of the cysteine ligands to the second zinc atom (Cys-100, -103, and -111) are alkylated in addition to Cys-46. This enzyme product rapidly denatures and cannot be crystallized under our conditions. This is an experimental indication that the intact noncatalytic zinc binding site contributes to the structural stability of the protein.
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PMID:X-ray analysis of structural changes induced by reduced nicotinamide adenine dinucleotide when bound to cysteine-46-carboxymethylated liver alcohol dehydrogenase. 293 54

The stereospecificity of the enzyme-dependent oxidation of alpha-[4R-2H]NADH has been determined for four dehydrogenases: two pro-R specific enzymes, pig heart malate dehydrogenase and yeast alcohol dehydrogenase; and two pro-S specific enzymes, rabbit muscle glycerol-3-phosphate dehydrogenase and Rhodopseudomonas spheroides 3-hydroxybutyrate dehydrogenase. In all cases, an enzyme-dependent and substrate-specific oxidation to alpha-NAD+ is observed with the stereochemistry of oxidation identical with that found for the oxidation of the correspondingly labeled beta-NADH. The ability of dehydrogenases from diverse sources to utilize alpha-NADH in a stereochemically competent fashion is discussed in relation to proposed interactions between the nicotinamide sugar moiety and active site residues or obligatory alignments of the pyridine and sugar moieties.
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PMID:The stereospecificity of oxidation of alpha-[4R-2H]NADH by dehydrogenases. 294 36

The geometry of seven NAD+ analogues bound to horse liver alcohol dehydrogenase (LADH) modified only in their nicotinamide group, have been studied using AMBER molecular mechanics energy-minimization procedures. Starting geometries were taken from X-ray crystallographic data for NAD+/Me2SO/LADH reported by Eklund and co-workers. In this study the NAD+ analogues were encaged by the constituent amino acids of the enzyme within a range of 0.6 nm from the initial NAD+/Me2SO/Zn2+ complex. The calculational method used is able to rationalize individual substituent effects and to evaluate the essential interactions between NAD+ analogue, enzyme, Me2SO and Zn2+ without the necessity of additional X-ray data. The results presented here demonstrate that the reactivity of NAD+ derivatives as reported in literature can be qualitatively related to the position of the pyridine moiety in the active site.
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PMID:Molecular mechanics calculation of geometries of NAD+ derivatives, modified in the nicotinamide group, in a ternary complex with horse liver alcohol dehydrogenase. 297 Mar 84

This paper reports some effects of temperature variation, nutritional stress and a novel alteration in energy availability upon larval fitness in Drosophila melanogaster. The cofactor nicotinamide adenine dinucleotide (NAD) has been chosen as a novel energy source to be supplemented in food during larval development. The effects have been assessed at the phenotypic level for larval survival and development time and at the genotypic level for the alcohol dehydrogenase (Adh) and glycerol-3-phosphate dehydrogenase (Gpdh) loci. Supplemented NAD was found to increase survival at the lower temperatures and decrease survival at the higher temperatures. Further, for each temperature, NAD decreased development time although this effect diminished as temperature increased. There were no significant effects at the genotypic level. Hence a phenotypic approach studying the effects of environmental stresses and novel energy availability may be useful in understanding fitness variation in Drosophila populations.
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PMID:Stress, altered energy availability and larval fitness in Drosophila melanogaster. 313 Mar 41

Various in vitro experiments were performed for the purpose of clarifying the mechanism of ethanol production in corpses. Whereas a negligible quantity of ethanol was produced in the blood alone, which was left at room temperature, the quantity of ethanol was slightly increased by addition of glucose to the blood. When saprogens were further added, the quantity was markedly increased. Various materials were added to blood-liver homogenates as specimens, and the mixtures were stored in an incubator at 37 degrees C. As a result of the addition of an antibiotic to the mixture every day, there was hardly any production of ethanol. When alcohol dehydrogenase (ADH) and reduced nicotinamide adenine dinucleotide (NADH) were added, ethanol production was slightly increased. When acetaldehyde was added first, ethanol production was inhibited the next day, but on and after day 2, the quantity of ethanol was more than that in the control material. When pyruvic acid was added first, the results were similar to the above. Pyrazole, cyanamide, and disulfiram completely inhibited the production of ethanol. Ethanol production in corpses is believed to take place through a pathway opposite to that of ethanol metabolism in the living body, under the influence of ADH, ALDH, etc., in saprogens using carbohydrates as substrates.
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PMID:Experimental studies on the mechanism of ethanol formation in corpses. 321 84


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