Fatty acid-dependent ethanol metabolism.
Rates of ethanol oxidation by perfused livers from fasted female rats were decreased from 82 +/- 8 to 11 +/- 7 mumol/g/hr by 4-methylpyrazole, an inhibitor of alcohol dehydrogenase. The subsequent addition of fatty acids of various chain lengths in the presence of 4-methylpyrazole increased rates of ethanol uptake markedly. Palmitate (1 mM) increased rates of ethanol oxidation to 95 +/- 8 mumol/g/hr, while octanoate and oleate increased rates to 58 +/- 11 and 68 +/- 15 mumol/g/hr, respectively. Hexanoate, a short-chain fatty acid oxidized predominantly in the mitochondria, had no effect. Addition of oleate also increased the steady-state level of catalase-H2O2. Pretreatment of rats for 1.5 hours with 3-amino-1,2,4-triazole (1.0 g/kg), an inhibitor of catalase, prevented the ethanol-dependent decrease in the steady-state level of catalase-H2O2 completely. Under these conditions, aminotriazole decreased rates of ethanol oxidation by about 50% and blocked the stimulation of ethanol oxidation by fatty acids. Oleate decreased rates of aniline hydroxylation by about 50%, indicating that cytochrome P450 is not involved in the stimulation of ethanol uptake by fatty acids. Furthermore, oleate stimulated ethanol uptake in livers from ADH-negative deermice indicating that fatty acids do not simply displace 4-methylpyrazole from alcohol dehydrogenase. It is concluded that the stimulation of ethanol oxidation by fatty acids is due to increased H2O2 supplied by the peroxisomal beta-oxidation of fatty acids for the catalase-H2O2 peroxidation pathway.
Handler
J A
JA
Thurman
R G
RG
D000426:Alcohol Dehydrogenase; D000429:Alcohol Oxidoreductases / Q000502:physiology; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002374:Catalase / Q000032:analysis; D003577:Cytochrome P-450 Enzyme System / Q000502:physiology; D000431:Ethanol / Q000378:metabolism*; D005227:Fatty Acids / Q000494:pharmacology*; D005260:Female; D006861:Hydrogen Peroxide / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D010542:Peromyscus; D051381:Rats; D011919:Rats, Inbred Strains
D000814:Aniline Compounds; D005227:Fatty Acids; D000431:Ethanol; D003577:Cytochrome P-450 Enzyme System; D006861:Hydrogen Peroxide; D000429:Alcohol Oxidoreductases; D000426:Alcohol Dehydrogenase; D002374:Catalase; C023650:aniline