Fatty acids supply H2O2 at high rates for the oxidation of ethanol by catalase.
Fatty acids are physiological substrates for H2O2 production via peroxisomal beta-oxidation and have been shown to increase ethanol metabolism markedly in a system that involves catalase-H2O2. To try to understand why fatty acid-stimulated ethanol uptake occurs much faster than rates of H2O2 generation reported previously, studies were conducted to measure these parameters under identical conditions in the perfused rat liver. New methods were developed to measure H2O2 generation in a recirculating perfusion system based on the fact that methanol is oxidized only by catalase in rat liver. One method for measuring H2O2 generation in the perfused liver was based on the linear decrease in the concentration of methanol per unit time and the stoichiometry between H2O2 production and methanol oxidation of nearly 1:1. A second method relied on quantitation of the time necessary for the steady-state level of catalase-H2O2 measured spectrophotometrically (660-640 nm) through a lobe of the liver to return to basal values following the addition of known quantities of methanol. Basal rates of H2O2 production measured with both new methods and rates of 4-methylpyrazole- insensitive ethanol oxidation were similar (9 to 17 mumol/g/hr). Rates of H2O2 generation were increased up to 80 mumol/g/hr by addition of oleate or palmitate (1 mM), values which compared well with rates of fatty acid-stimulated palmitate (1 mM), values which compared well with rates of fatty acid-stimulated ethanol uptake of 70 to 90 mumol/g/hr measured in the presence of 4-methylpyrazole.(ABSTRACT TRUNCATED AT 250 WORDS)
Handler
J A
JA
Department of Pharmacology, University of North Carolina, Chapel Hill 27514.
Thurman
R G
RG
D000818:Animals; D002374:Catalase / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000493:pharmacokinetics*; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats
D005227:Fatty Acids; D000431:Ethanol; D006861:Hydrogen Peroxide; D002374:Catalase