Increased formation of short-chain organic acids after chronic ethanol administration and its interaction with the carnitine pool in rat.
Organic acidurias are genetic disorders of mitochondrial metabolism that lead to the accumulation of organic acids in tissues and biological fluids. It has been demonstrated that interaction of carnitine with the cellular coenzyme A (CoA) pool, through the production of acyl-carnitines, is potentially critical for maintaining normal cellular metabolism under condition of impaired acyl-CoA use and that exposure of humans and other mammals to ethanol leads to impairment of mitochondrial function. The aim of the present study was to evaluate the role of chronic administration of ethanol on urinary excretion of short-chain organic acids and endogenous carnitines in rats. The data reported show that chronic administration of ethanol significantly increases urinary excretion of propionate, methylmalonate, as well as free acetate, butyrate, pyruvate, lactate, and beta-hydroxybutyrate. Chronic administration of propranolol abolished ethanol-dependent accumulation of propionate, suggesting involvement of beta-adrenergic mechanisms. Increased formation of propionate and methylmalonate was associated with decreased plasma carnitine levels and with increased excretion of specific acyl-carnitines, corresponding to the accumulating acyl groups. Our data indicate that chronic alcohol ingestion induces increased excretion of selected organic acids and that the endogenous carnitine pool might exert a protective role against the deleterious effects of accumulating short-chain organic acids.
Calabrese
Vittorio
V
Department of Chemistry, Biochemistry & Mol. Biology Section, Faculty of Medicine, University of Catania, Viale A. Doria 6, 95125 Catania, Italy. calabres@mbox.unict.it
Calvani
Menotti
M
Butterfield
D Allan
DA
D000144:Acids, Acyclic / Q000652:urine*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002331:Carnitine / Q000097:blood / Q000652:urine*; D002492:Central Nervous System Depressants / Q000008:administration & dosage* / Q000494:pharmacology; D004334:Drug Administration Schedule; D000431:Ethanol / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D011422:Propionates / Q000652:urine; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000144:Acids, Acyclic; D000319:Adrenergic beta-Antagonists; D002492:Central Nervous System Depressants; D011422:Propionates; D000431:Ethanol; D008764:Methylmalonic Acid; D011433:Propranolol; D002331:Carnitine