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)

1,4,5,6-Tetrahydronicotinamide adenine dinucleotide (H2NADH) has been investigated as a reduced coenzyme analog in the reaction between trans-4-N,N-dimethylaminocinnamaldehyde (I) (lambdamax 398 nm, epsilonmax 3.15 X 10-4 M-minus 1 cm-minus 1) and the horse liver alcohol dehydrogenase-NADH complex. These equilibrium binding and temperature-jump kinetic studies establish the following. (i) Substitution of H2NADH for NADH limits reaction to the reversible formation of a new chromophoric species, lambdamax 468 nm, epsilonmax 5.8 x 10-4 M-minus 1 cm-minus 1. This chromophore is demonstrated to be structurally analogous to the transient intermediate formed during the reaction of I with the enzyme-NADH complex [Dunn, M. F., and Hutchison, J. S. (1973), Biochemistry 12, 4882]. (ii) The process of intermediate formation with the enzyme-NADH complex is independent of pH over the range 6.13-10.54. Although studies were limited to the pH range 5.98-8.72, a similar pH independence appears to hold for the H2NADH system. (iii) Within the ternary complex, I is bound within van der Waal's contact distance of the coenzyme nicotinamide ring. (iv) Formation of the transient intermediate does not involve covalent modification of coenzyme. Based on these findings, we conclude that zinc ion has a Lewis acid function in facilitating the chemical activation of the aldehyde carbonyl for reduction, and that reduced coenzyme plays a noncovalent effector role in this substrate activating step.
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PMID:Roles of zinc ion and reduced coenzyme in horse liver alcohol dehydrogenase catalysis. The mechanism of aldehyde activation. 23 85

Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system. Since the major fraction of ethanol metabolism proceeds via alcohol dehydrogenase and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate microsomal ethanol oxidizing system pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Severe hepatic lesions (alcoholic hepatitis and cirrhosis) develop after prolonged ethanol consumption in baboons. These injurious alterations are not prevented by nutritionally adequate diets and can therefore be ascribed to ethanol rather than to dietary inadequacy.
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PMID:Differences in hepatic and metabolic changes after acute and chronic alcohol consumption. 24 Jul 42

Hepatic metabolism of ethanol to acetaldehyde by the alcohol dehydrogenase (ADH) pathway is associated with the generation of reducing equivalents as NADH. Conversely, reducing equivalents are consumed when ethanol oxidation is catalyzed by the NADPH dependent microsomal ethanol oxidizing system (MEOS). Since the major fraction of ethanol metabolism proceeds via ADH and since the oxidation of acetaldehyde also generates NADH, an excess of reducing equivalents is produced. This explains a variety of effects following acute ethanol administration, including hyperlactacidemia, hyperuricemia, enhanced lipogenesis and depressed lipid oxidation. To the extent that ethanol is oxidized by the alternate MEOS pathway, it slows the metabolism of other microsomal substrates. Following chronic ethanol consumption, adaptive microsomal changes prevail, which include enhanced ethanol and drug metabolism, and increased lipoprotein production. Eventually, injury develops with alterations of the rough endoplasmic reticulum and structural and functional abnormalities of the mitochondria.
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PMID:Effect of chronic alcohol consumption on ethanol and acetaldehyde metabolism. 24 Dec 14

The kinetics of ethanol oxidation by NAD+, and acetaldehyde and butyraldehyde reduction by NADH, catalysed by yeast alcohol dehydrogenase, were studied in the pH range 4.9--9.9 at 25 degrees C and in the temperature range 14.8--43.5 degrees C at pH 7.05. The kinetics of reduction of acetaldehyde by [4A-2H]NADH at pH 7.05 and pH 8.9 at 25 degrees C were also studied. The results of the kinetic experiments indicate that the mechanism of catalysis, previously proposed on the basis of studies at pH 7.05 and 25 degrees C (Dickinson & Monger, 1973), applies over the wide range of conditions now tested. Values of some of the initial-rate parameters obtained were used to deduce information about the pH- and temperature-dependence of the specific rates of combination of enzyme and coenzymes and of the dissociation of the enzyme--coenzyme compounds. Primary and secondary plots of initial-rate data are deposited as Supplementary Publication SUP 50043 (20 pages) with the British Library (Lending Division), Boston Spa, Wetherby, Yorks. LS23 7BQ, U.K., from whom copies may be obtained under the terms indicated in Biochem. J. (1975) 145, 5.
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PMID:A study of the pH- and temperature-dependence of the reactions of yeast alcohol dehydrogenase with ethanol, acetaldehyde and butyraldehyde as substrates. 24 23

15-Hydroxyprostaglandin dehydrogenase was isolated from human term placenta up to a final purification of 380-fold. A spec. act. of 2000 mU/mg of protein was reached. The preparation was not homogeneous as judged by analytical disc electrophoresis. The enzyme could be stored in the presence of 50% glycerol and 10mM 2-mercaptoethanol without any loss of activity for at least one year. A distinct single protein band stained after discontinuous polyacrylamide gel electrophoresis was shown by enzymatic activity staining to correspond to 15-hydroxyprostaglandin dehydrogenase activity. Thus no evidence for the exitstence of isoenzymes was obtained. The protein in the final preparation steps showed neither alcohol dehydrogenase, NAD reductase, nor NADH oxidase activity, nor enzymatic conversion of prostaglandin or 15-oxoprostaglandin in the absence of NAD and NADH. No spontaneous reactions between NAD and prostaglandin or NADH and 15-oxoprostaglandin were detectable in the absence of the enzyme. Ethanol and glycerol slightly inhibited the reaction. Various buffers (Tris/HC1, potassium phosphate, HEPES, and triethanolamine) and salts (ammonium chloride, ammonium sulfate, potassium chloride, and sodium chloride) had different effects on the reaction rate. The pH profile of the reaction shows a plateau between pH 7.0 and 7.8 and a steep maximum at pH 9.5. A linear Arrhenius plot was obtained for the temperature dependence of the reaction from 20 to 37 degrees C. The molar activation enthalpy of the reaction was calculated to be 13.1 kcal/mole. The molecular weight of 15-hydroxyprostaglandin dehydrogenase was estimated to be 32000 -/+ 3000 by gel filtration on Sephadex G-150 in the presence of 10mM mercaptoethanol.
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PMID:[15-Hydroxyprostaglandin dehydrogenase from human placenta. 1. Isolation and characterization]. 24 91

Repeated selection of petite (respiratorily incompetent) Saccharomyces cerevisiae on medium containing allyl alcohol, both on plates and in the turbidostat, results in mutants with a remarkably similar response. Most of the mutations affect the constitutive alcohol dehydrogenase, resulting in enzymes with a cathodal shift in electrophoretic mobility, and none shows a significant anodal shift. The genetics, kinetics, and physiological effect of three of the mutants have been investigated in detail, and while all confer resistance to allyl alcohol through a shift in the NAD/NADH ratio, they do so in slightly different ways. The potential of this system for exploring the range of short-term adaptations open to this organism is discussed.
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PMID:Functional mutants of yeast alcohol dehydrogenase affecting kinetics, cellular redox balance, and electrophoretic mobility. 36 61

The effect of long-term administration of phenobarbital (PB) or barbital for five weeks on brain aldehyde reductase (A1R) and aldehyde dehydrogenase (A1DH) activities in the rat was studied. Mitochondrial (m)-A1DH and NADH-dependent A1R activities were significantly increased over control values after five-week treatment with PB or barbital, while no significant alteration of supernatant (s)-A1DH and NADPH-dependent A1R activities was observed under the same condition. Increase in m-A1DH activity by the treatment with barbiturates was recovered to the control level, however, increased activity of NADH-dependent A1R was maintained even after the cessation of the treatment. In groups of rats pretreated with barbiturates for five weeks, no animals were induced to sleep after intracerebroventricular injection of PB, and this finding strongly suggests the decrease in sensitivity of rats to barbiturates.
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PMID:Induction of NADH-dependent aldehyde reductase by successive administration of barbiturates in rat brain. 46 55

The rate of ethanol elimination in vivo was studied with rats in which the energy consumption of the liver was increased by partial hepatectomy. Immediately after partial hepatectomy the activity of alcohol dehydrogenase in the liver remnant was not changed from that of the livers of sham-operated controls, but the rate of ethanol removal was significantly faster. Twenty-four h after the partial hepatectomy the activity of alcohol dehydrogenase was only 48 % of the activity measured in unoperated control rats. Therefore it is concluded that in normal liver the activity of ADH is in excess. In partially hepatectomized rats the rate of ethanol elimination was linearly correlated with the activity of alcohol dehydrogenase, which suggests that when the rate of NADH reoxidation is markedly increased, as in regenerating rat liver, the rate of ethanol elimination may be limited by the activity of alcohol dehydrogenase. The activity of aldehyde dehydrogenase and the concentration of acetaldehyde in the tail blood were not significantly changed from the level of unoperated rats during oxidation of ethanol.
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PMID:Ethanol elimination in regenerating rat liver: the roles of alcohol dehydrogenase and acetaldehyde. 46 53

Low concentrations of ethanol (0.2 mM) stimulated p-nitroanisole O-demethylation in perfused livers from fasted, but not fed, phenobarbital-treated rats. The increase in mixed-function oxidation correlated well with the production of NADH from ethanol metabolism (Ka for both processes = 0.2-0.3 mM). This stimulation by ethanol was blocked by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase, and pyruvate, a substrate for lactate dehydrogenase. Under these conditions, the characteristic reduction of NAD+ by ethanol was also abolished. p-Nitroanisole O-demethylation by isolated hepatic microsomes was unaffected by low concentrations of ethanol (up to 2 mM); however, when NADH was added to the microsomes, or was generated from ethanol, alcohol dehydrogenase and NAD+, a synergistic increase in p-nitroanisole metabolism occurred. Sorbitol and xylitol, two carbohydrates which reduced pyridine nucleotides in perfused livers, also stimulated p-nitroanisole O-demethylation in livers from fasted rats. The data indicate that NADH produced from the metabolism of ethanol, sorbitol and xylitol stimulates mixed-function oxidation in livers from fasted animals.
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PMID:Stimulation of p-nitroanisole O-demethylation by ethanol in perfused livers from fasted rats. 49 Mar 14

Simple models were developed to study changes in oxygen uptake in perfused rat liver and increases in ethanol metabolism in vivo. Results obtained 2.5 hours following a large dose of ethanol were quantitatively similar to those seen after 24 hours or 5 weeks. The rapidity of the increase indicated that SIAM represents an activation rather than an adaptation. Pathways responsible for the swift increase in alcohol metabolism (SIAM) in the perfused rat liver were investigated through the use of ouabain and were found to be related to diminished glycolysis and another unidentified pathway. Investigation of pathways responsible for the increase in ethanol metabolism in vivo following ethanol treatment implicated the alcohol dehydrogenase pathway as that mainly responsible for the adaptive increase, although a catalase-H2O2-dependent component was also involved. The rate of NADH reoxidation generally appeared to be the rate-limiting step. In addition, the genetic aspect of SIAM was indicated through selective breeding resulting in F1 generations of non-SIAM and SIAM rats.
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PMID:The adaptive increase in ethanol metabolism due to pretreatment with ethanol: a rapid phenomenon. 51 Jan 61


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