title: In vivo roles of alcohol dehydrogenase (ADH), catalase and the microsomal ethanol oxidizing system (MEOS) in deermice.
abstract: The relative importance of ADH and MEOS for ethanol oxidation in the liver has yet to be elucidated. The discovery of a strain of deermice genetically lacking ADH (ADH-) which can consume ethanol at greater than 50% of the rates seen in deermice having ADH (ADH+) suggested a significant role for non-ADH pathways in vivo. To quantitate contributions of the various pathways, we examined first the ethanol oxidation rates with or without 4-methylpyrazole in isolated deermice hepatocytes. 4-Methylpyrazole significantly reduced the ethanol oxidation in both ADH+ and ADH- hepatocytes. The reduction seen in ADH- cells can be applied to correct for the effect of 4-methylpyrazole on non-ADH pathways of ADH+ deermouse hepatocytes. After correction, non-ADH pathways were found to contribute 28% of ethanol metabolism at 10 mM and 52% at 50 mM. When using a different approach namely measurement of the isotope effect, MEOS was calculated to account for 35% at low and about 70% at high blood ethanol concentrations. Thus, we found that two different complementary approaches yielded similar results, namely that non-ADH pathways play a significant role in ethanol oxidation even in the presence of ADH.
authors.forename: T
authors.initials: T
authors.lastname: Takagi
authors.forename: J
authors.initials: J
authors.lastname: Alderman
authors.forename: C S
authors.initials: CS
authors.lastname: Lieber
mesh_terms: D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000037:antagonists & inhibitors / Q000502:physiology*; D000818:Animals; D002374:Catalase / Q000502:physiology*; D003903:Deuterium; D000431:Ethanol / Q000378:metabolism*; D008862:Microsomes, Liver / Q000378:metabolism*; D010084:Oxidation-Reduction; D010542:Peromyscus; D014316:Tritium
chemical_list: D014316:Tritium; D000431:Ethanol; D003903:Deuterium; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D002374:Catalase