| Ethanol-metabolizing pathways in deermice. Estimation of flux calculated from isotope effects. | |
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MedLine Citation:
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PMID: 3294834 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The apparent deuterium isotope effects on Vmax/Km (D(V/K] of ethanol oxidation in two deermouse strains (one having and one lacking hepatic alcohol dehydrogenase (ADH] were used to calculate flux through the ADH, microsomal ethanol-oxidizing system (MEOS), and catalase pathways. In vitro, D(V/K) values were 3.22 for ADH, 1.13 for MEOS, and 1.83 for catalase under physiological conditions of pH, temperature, and ionic strength. In vivo, in deermice lacking ADH (ADH-), D(V/K) was 1.20 +/- 0.09 (mean +/- S.E.) at 7.0 +/- 0.5 mM blood ethanol and 1.08 +/- 0.10 at 57.8 +/- 10.2 mM blood ethanol, consistent with ethanol oxidation principally by MEOS. Pretreatment of ADH- animals with the catalase inhibitor 3-amino-1,2,4-triazole did not significantly change D(V/K). ADH+ deermice exhibited D(V/K) values of 1.87 +/- 0.06 (untreated), 1.71 +/- 0.13 (pretreated with 3-amino-1,2,4-triazole), and 1.24 +/- 0.13 (after the ADH inhibitor, 4-methylpyrazole) at 5-7 mM blood ethanol levels. At elevated blood ethanol concentrations (58.1 +/- 2.4 mM), a D(V/K) of 1.37 +/- 0.21 was measured in the ADH+ strain. For measured D(V/K) values to accurately reflect pathway contributions, initial reaction conditions are essential. These were shown to exist by the following criteria: negligible fractional conversion of substrate to product and no measurable back reaction in deermice having a reversible enzyme (ADH). Thus, calculations from D(V/K) indicate that, even when ADH is present, non-ADH pathways (mostly MEOS) participate significantly in ethanol metabolism at all concentrations tested and play a major role at high levels. |
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Authors:
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J Alderman; T Takagi; C S Lieber |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 262 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1987 Jun |
Date Detail:
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Created Date: 1987-07-02 Completed Date: 1987-07-02 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 7497-503 Citation Subset: IM |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Acetates
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metabolism Alcohol Dehydrogenase / genetics, metabolism* Animals Carbon Radioisotopes Deuterium Ethanol / metabolism* Kinetics Liver / metabolism Male Peromyscus / metabolism* Radioisotope Dilution Technique Rats Rats, Inbred Strains Species Specificity |
| Grant Support | |
ID/Acronym/Agency:
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AA03508/AA/NIAAA NIH HHS; AA05934/AA/NIAAA NIH HHS; AA07275/AA/NIAAA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Acetates; 0/Carbon Radioisotopes; 64-17-5/Ethanol; 7782-39-0/Deuterium; EC 1.1.1.1/Alcohol Dehydrogenase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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