Uncoupling of oxidative phosphorylation prevents the urinary alcohol level cycling caused by feeding ethanol continuously at a constant rate.
The mechanism of the UAL cycle in the intragastric feeding model of alcoholic liver disease in the rat was investigated by administering dinitrophenol (DNP) with ethanol in the diet. The question was: is the rate of oxidative phosphorylation fluxuation essential for the cycle to occur? The question has been partially answered by showing that rotenone, which inhibits complex I, blocks the cycle by preventing the generation of NAD from NADH. This would inhibit ATP generation from complex I but would not affect oxidative phosphorylation by complex 2 and 3. Since the rate of O2 consumption is normal at the troughs of the cycle and decreases at the peaks of the cycle and the levels of ATP are reduced at the peaks of the cycle, it is likely that the rate of oxidative phosphorylation also cycles. Since 2-4 dinitrophenol (DNP) uncouples oxidative phosphorylation, it was anticipated that feeding it with ethanol would prevent the cycle from occurring. This proved to be the case. In addition, DNP caused energy wasting and prevented the increase in serum alanine aminotranspeptidase caused by ethanol feeding, probably by preventing the hypoxia which occurs at the peaks of the cycle.
Li
J
J
Department of Pathology, Harbor-UCLA Medical Center, 1000 W. Carson St., Torrance, CA 90509, USA.
French
B A
BA
Nan
L
L
Fu
P
P
French
S W
SW
D019297:2,4-Dinitrophenol / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D000431:Ethanol / Q000009:adverse effects / Q000097:blood / Q000652:urine*; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008108:Liver Diseases, Alcoholic / Q000473:pathology*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D014475:Uncoupling Agents / Q000494:pharmacology
D014475:Uncoupling Agents; D000431:Ethanol; D019297:2,4-Dinitrophenol