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)

4-Methyl pyrazole (4-MP, a specific inhibitor of alcohol dehydrogenase) reduced ethanol elimination by 30-50% and completely removed the ethanol-induced inhibition of galactose elimination in 2 control subjects. Ethanol elimination was accelerated in 2 alcoholics with adequate nutrition, but the effect of 4-MP was comparable to that in controls. In 2 other alcoholic subjects, who reported poor nutritional intake, intermediate rates of ethanol elimination were observed and 4-MP had almost no effect on ethanol or galactose elimination. These results suggest that alcohol abuse may result in an increased contribution to ethanol elimination by pathways other than that involving alcohol dehydrogenase (ADH) and that the decreased contribution from ADH, possibly potentiated by inadequate nutrition, may diminish the ethanol-induced shift in the NAD-coupled redox state. Since liver damage produced by alcohol abuse is believed to be related to changes from the normal redox state caused by ethanol, these results may explain why alcoholic liver damage is uncommon in alcoholics living on a marginal diet. Since 4-MP effectively eliminates the ethanol-induced shift in the redox state, a therapeutic trial with 4-MP in alcoholics with a high risk for liver disease is indicated.
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PMID:Ethanol and galactose metabolism as influenced by 4-methylpyrazole in alcoholics with and without nutritional deficiencies. Preliminary report of a new approach to pathogenesis and treatment in alcoholic liver disease. 0 33

1. The effects of hypertonic saline infusion into the third ventricle were investigated in ten monkeys which were pre-operated, trained, and used in the conscious state under controlled conditions. 2. In non-hydrated monkeys, intraventricular infusion of NaCl 1.0 M, 0.01 ml./min for 30 min did not affect urine volume or Na output but produced a small increase in urine osmolality. Comparable infusion of NaCl 0.15 M had no effect on any parameter. 3. In monkeys undergoing water diuresis (with i.v. infusion of 5% dextrose), intraventricular hypertonic saline produced large reciprocal changes in urine volume and osmolality while urine Na showed no significant change. The effects on urine volume and osmolality were greater than those of lysine-vasopressin 30 m-u./kg i.v. 4. The absence of natriuresis after intraventricular hypertonic saline infusion in the monkey was in notable contrast to the results reported in lower species. However, the data suggested that the infusion probably released ADH as in other species.
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PMID:Search for a natriuretic mechanism sensitive to sodium in the brain of the monkey. 41 58

The activities of key enzymes that are members of D-glucose metabolic pathways in Schizosaccharomyces pombe undergoing respirative, respirofermentative, and fermentative metabolisms are monitored. The steady-state activities of glycolytic enzymes, except phosphofructokinase, decrease with a reduced efficiency in D-glucose utilization by yeast continuous culture. On the other hand, the enzymic activities of pentose monophosphate pathway reach the maximum when the cell mass production of the cultures is optimum. Enzymes of tricarboxylate cycle exhibit the maximum activities at approximately the washout rate. The steady-state activity of pyruvate dehydrogenase complex increases rapidly when D-glucose is efficiently utilized. By comparison, the activity of pyruvate decarboxylase begins to increase only when ethanol production occurs. Depletion of dissolved oxygen suppresses the activity of pyruvate dehydrogenase complex but facilitates that of pyruvate decarboxylase. Acetate greatly enhances the acetyl CoA synthetase activity. Similarly, ethanol stimulates alcohol dehydrogenase and aldehyde dehydrogenase activities. Evidence for the existence of alcohol dehydrogenase isozymes in the fission yeast is presented.
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PMID:Enzyme activities of D-glucose metabolism in the fission yeast Schizosaccharomyces pombe. 128 48

In order to obtain large quantities of extremely pure human asparagine synthetase for detailed kinetic and structural studies, its gene was cloned into a 2mu plasmid (pBS24.1GAS) suitable for replication in a Saccharomyces cerevisiae cir0 strain (AB116). In this construct, the transcription of the asparagine synthetase gene is regulated by the alcohol dehydrogenase II/glyceraldehyde-3-phosphate dehydrogenase promoter, which is subject to glucose repression. The expression of the enzyme was allowed to take place in yeast minimal medium containing D-galactose as the only sugar nutrient. Eleven monoclonal antibodies to recombinant human asparagine synthetase were produced and one of them was selected to make immunoaffinity resins. After single-step immunoaffinity chromatography, more than 1.2 mg of homogeneous enzyme was obtained from the total cell extract from a 100-ml yeast culture. The yield of pure enzyme was over 100-fold higher than that of a previously reported yeast expression system. SDS-PAGE analysis showed the enzyme to be extremely pure and isoelectric focusing gel electrophoresis showed that the enzyme has an isoelectric point of 7.5. Immunoaffinity-purified recombinant human asparagine synthetase demonstrated both glutamine-dependent and ammonia-dependent asparagine synthetase activities, as well as glutaminase activity.
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PMID:High-level expression of human asparagine synthetase and production of monoclonal antibodies for enzyme purification. 135 3

Mounting evidence indicates that aldose reductase catalyzed reduction of excess glucose to sorbitol initiates the onset of certain diabetic complications. However, the kidney contains a large amount of aldehyde reductase, another NADPH-dependent reductase. The study was designed to assess the importance of these reductases to sugar alcohol (polyol) production in the kidney. To study the ability to reduce aldoses to polyols, both aldose and aldehyde reductases were purified from rat kidneys. Incubation studies with purified enzymes clearly demonstrated the polyol formation by both enzymes. Galactose feeding induced polyol accumulation in both medulla and cortex of the rat kidney. Al 1576, a potent inhibitor of both enzymes, reduced this polyol accumulation in both cortex and medulla, while the selective inhibitors Ponalrestat or FK 366 resulted in greater inhibition in medulla than cortex. These results suggest that kidney polyols may be generated by both aldose and aldehyde reductases and that aldehyde reductase contributes to polyol production in the kidney cortex, the predominant site of diabetes-linked kidney lesions.
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PMID:Rat kidney aldose reductase and aldehyde reductase and polyol production in rat kidney. 144 70

Constitutive expression of human nuclear NAD+: protein ADP-ribosyltransferase (polymerizing) [pADPRT; poly(ADP-ribose)polymerase; EC 2.4.2.30] as an active enzyme in Saccharomyces cerevisiae, under the control of the alcohol dehydrogenase promoter, was only possible with simultaneous inhibition of ADP-ribosylation by 3-methoxybenzamide. Induction of fully active pADPRT from the inducible galactose epimerase promoter resulted in inhibition of cell division and morphological changes reminiscent of cell cycle mutants. Expression of a pADPRT cDNA truncated at its 5' end had no influence on cell proliferation at all. Obviously the amino-terminal part of the DNA binding domain containing the first "zinc finger", which is essential for inducibility of pADPRT activity by DNA breaks, is also required for inhibition of cell growth on expression in yeast. Full-length as well as truncated pADPRT molecules were directed to the cell nucleus where the fully active enzyme produced large amounts of poly(ADP-ribose) by automodification. Since pADPRT turned out to be the only target for ADP-ribosylation in these cells, elevated levels of poly(ADP-ribose) were the most likely cause of inhibition of cell division, presumably resulting from interaction with chromosomal proteins.
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PMID:Inhibition of cell proliferation in Saccharomyces cerevisiae by expression of human NAD+ ADP-ribosyltransferase requires the DNA binding domain ("zinc fingers"). 155 29

The xylanase(XLN)-encoding gene(XLN) of Cryptococcus albidus and its cDNA were each inserted into the vector, pVT100, for expression in Saccharomyces cerevisiae. Expression was under the control of either their own promoter or the gene encoding alcohol dehydrogenase (ADH1) promoter. Yeast transformed with plasmids containing the cDNA of the structural XLN gene and the XLN promoter produced active extracellular XLN when grown with galactose as carbon source. However, with glucose as carbon source, XLN was repressed. Using the ADH1 promoter, which is stimulated by glucose, XLN was secreted into the culture medium. In both cases, the secreted 48-kDa enzyme corresponded to the native XLN produced by C. albidus. With the plasmid bearing the genomic XLN gene, there was transcription, but the seven introns interrupting XLN were not spliced out by S. cerevisiae and no enzyme was produced.
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PMID:Secretion of a Cryptococcus albidus xylanase in Saccharomyces cerevisiae. 162 37

An efficient, large-scale purification has been achieved for two aldose reductase isoenzymes from human placenta in stable form. The procedure included ammonium sulfate fractionation (45-75%), followed by chromatographies on Matrex Red A, DE-52 cellulose, and Matrex Orange A. The preparations were stable for at least 3 months at 3 degrees C. IC50 values toward sorbinil were similar to those reported for crude or partially purified enzymes, indicating that they retained native structures during the purification steps. The molecular weights of purified GAR1 and GAR2, named according to their order of elution with a salt gradient from a Matrex Red A column, were 36,600 and 40,300, respectively. Kinetic studies indicate that GAR1 belongs to an aldose reductase (a low-Km form) and GAR2 to an aldehyde reductase (a high-Km form). GAR2, an aldehyde reductase, was also active in the reduction of D-glucose, with an apparent Km comparable to that of GAR1 but with a Vmax only 14% that of GAR1.
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PMID:Stable preparation of aldose reductase isoenzymes from human placenta. 182 16

1. Aldose reductase and aldehyde reductase were purified to homogeneity from human testis. 2. The molecular weight of aldose reductase and aldehyde reductase were estimated to be 36,000 and 38,000 by SDS-PAGE, and the pI values of these enzymes were found to be 5.9 and 5.1 by chromatofocusing, respectively. 3. Aldose reductase had activity for aldo-sugars, whereas aldehyde reductase was virtually inactive for aldo-sugars. The Km values of aldose reductase for D-glucose, D-galactose and D-xylose were 57, 49 and 6.2 mM, respectively. Aldose reductase utilized both NADPH and NADH as coenzymes, whereas aldehyde reductase only NADPH. 4. Sulfate ion caused 3-fold activation of aldose reductase, but little for that of aldehyde reductase. 5. Sodium valproate inhibited significantly aldehyde reductase, but not aldose reductase. Aldose reductase was inhibited strongly by aldose reductase inhibitors being in clinical trials at concentrations of the order of 10(-7)-10(-9) M. Aldehyde reductase was also inhibited by these inhibitors, but its susceptibility was less than aldose reductase. 6. Reaction of aldose reductase with pyridoxal 5'-phosphate (PLP) resulted ca 2.5-fold activation, but aldehyde reductase did not cause the activation. PLP-treated aldose reductase has lost the susceptibility to aldose reductase inhibitor.
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PMID:Purification and characterization of human testis aldose and aldehyde reductase. 190 6

Three kinds of NADPH-dependent aldehyde reducing enzymes were present in the dog kidney. Aldose reductase was located in the inner medulla region and aldehyde reductase in all regions of the renal cortex, outer medulla and inner medulla. In addition, a new reductase designated tentatively as high-Km aldose reductase, which was converted into an aldose reductase-like enzyme, was present in the inner medulla region of the kidney. Aldose reductase, aldehyde reductase and high-Km aldose reductase were purified to homogeneity from each region of the dog kidney. The molecular weight of aldose reductase was estimated to be 38,500 by SDS-polyacrylamide gel electrophoresis and the isoelectric point was found to be 5.7 by chromatofocusing. Aldose reductase had activity for aldo-sugars such as D-xylose, D-glucose and D-galactose as substrates and utilized both NADPH and NADH as coenzymes. Sulfate ions resulted in over 2-fold activation of aldose reductase. All aldehyde reductases from the three regions had the same properties. The molecular weights and isoelectric points of aldehyde reductases were 40,000 and 6.1, respectively. The aldehyde reductases were inactive for D-hexose, utilized only NADPH as coenzyme and were not affected by sulfate ions. High-Km aldose reductase had a molecular weight of 38,500 and an isoelectric point of 5.4. It had activity for aldo-sugars, but showed much higher Km and lower kcat/Km values than aldose reductase. Sulfate ions inhibited high-Km aldose reductase. It was converted into an aldose reductase-like enzyme by incubation in phosphate buffer at pH 7.0. The three kinds of enzymes were strongly inhibited by the known aldose reductase inhibitors. However, aldehyde reductase and high-Km aldose reductase were, in general, less susceptible than aldose reductase.
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PMID:Localization, isolation and properties of three NADPH-dependent aldehyde reducing enzymes from dog kidney. 190


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