The mechanism(s) of the alcohol-induced impairment in glycogen synthesis in oxidative skeletal muscles.
Ethanol is known to acutely inhibit glucose-stimulated glycogen deposition in skeletal muscles in the rat. This effect is selective for oxidative as opposed to non-oxidative muscles. This paper explores the biochemical basis for this selective impairment in muscle glycogen metabolism. 4-Methylpyrazole, a potent inhibitor of alcohol dehydrogenase, potentiated the ethanol-mediated impairment in glycogen deposition in oxidative muscles and was associated with abnormalities in glycogen deposition in non-oxidative muscles. By contrast, disulfiram, a potent inhibitor of aldehyde dehydrogenase had no effect on the ethanol-mediated impairment in glycogen deposition in both oxidative and non-oxidative muscles. The implication is that it is the ethanol molecule itself, and not one of its metabolites (acetaldehyde, acetate, excess NADH), that mediates the defect in glycogen metabolism.
Xu
D
D
Department of Biochemistry, University of Western Australia, Nedlands.
Heng
J K
JK
Palmer
T N
TN
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004221:Disulfiram / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000633:toxicity*; D000077604:Fomepizole; D006003:Glycogen / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D010084:Oxidation-Reduction; D011720:Pyrazoles / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar
D001786:Blood Glucose; D011720:Pyrazoles; D000431:Ethanol; D000077604:Fomepizole; D006003:Glycogen; D004221:Disulfiram