Assessment of the role of non-ADH ethanol oxidation in vivo and in hepatocytes from deermice

Biochemical Pharmacology
T TakagiC S Lieber

Abstract

Deermice genetically lacking alcohol dehydrogenase (ADH-) were used to quantitate the effect of 4-methylpyrazole (4-MP) on non-ADH pathways in hepatocytes and in vivo. Although primarily an inhibitor of ADH, 4-methylpyrazole was also found to inhibit competitively the activity of the microsomal ethanol-oxidizing system (MEOS) in deermouse liver microsomes. The degree of 4-MP inhibition in ADH- deermice then served to correct for the effect of 4-MP on non-ADH pathways in deermice having ADH (ADH+). In ADH+ hepatocytes, the percent contributions of non-ADH pathways were calculated to be 28% at 10 mM and 52% at 50 mM ethanol. When a similar correction was applied to in vivo ethanol clearance rates in ADH+ deermice, non-ADH pathways were found to contribute 42% below 10 mM and 63% at 40-70 mM blood ethanol. The catalase inhibitor 3-amino-1,2,4-triazole, while reducing catalase-mediated peroxidation of ethanol by 83-94%, had only a slight effect on blood ethanol clearance at ethanol concentrations below 10 mM, and no effect at all at 40-70 mM ethanol. These results indicate that non-ADH pathways (primarily MEOS) play a significant role in ethanol oxidation in vivo and in hepatocytes in vitro.

References

Jan 1, 1977·Alcoholism, Clinical and Experimental Research·K E CrowR L Veech
Jan 1, 1977·Alcoholism, Clinical and Experimental Research·R TeschkeC S Lieber
Jul 1, 1969·Biochemical Pharmacology·L Goldberg, U Rydberg
Jan 1, 1970·Enzymologia Biologica Et Clinica·J PapenbergH Aebi
Jul 1, 1972·The Biochemical Journal·A BoverisB Chance
Jan 1, 1983·Alcoholism, Clinical and Experimental Research·C DelmasJ F Biellmann
Nov 1, 1983·Archives of Biochemistry and Biophysics·N W CornellK Henegar
Apr 1, 1984·Archives of Biochemistry and Biophysics·B V PlappB P Murch
Feb 1, 1980·Biochemical Pharmacology·K G Burnett, M R Felder
Jul 1, 1956·The American Journal of Physiology·D APPLEMANH T PYFROM

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Citations

Jan 1, 1989·Biochemical Pharmacology·M Hagman, R Jagenburg
Jan 3, 1997·Clinica Chimica Acta; International Journal of Clinical Chemistry·C S Lieber
Feb 1, 1990·Alcoholism, Clinical and Experimental Research·N InatomiC S Lieber
Dec 1, 1992·Alcoholism, Clinical and Experimental Research·S P Tam
Aug 1, 1993·Alcoholism, Clinical and Experimental Research·D Ito, C S Lieber
Jan 1, 1987·Annals of the New York Academy of Sciences·C S LieberM A Leo
Mar 15, 2005·Clinics in Liver Disease·Charles S Lieber
Jan 1, 1989·Drug Metabolism Reviews·R G Thurman, J A Handler
Jan 1, 1986·Alcoholism, Clinical and Experimental Research·R Teschke, J Gellert
Aug 3, 2000·Alcoholism, Clinical and Experimental Research·E BaraonaC S Lieber
Sep 1, 1990·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H MoshageC S Lieber
May 30, 2017·Frontiers in Behavioral Neuroscience·Alessandra T PeanaElio Acquas
Dec 1, 1987·Archives of Biochemistry and Biophysics·M A LeoC S Lieber
Aug 30, 1989·Biochemical and Biophysical Research Communications·N InatomiC S Lieber

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