Formation of propionate after short-term ethanol treatment and its interaction with the carnitine pool in rat.
Organic acidurias are genetic disorders of mitochondrial metabolism that lead to the accumulation in tissues and biological fluids of organic acids. It has been demonstrated that interaction of carnitine with the cellular CoA pool, through the production of acyl-carnitines, is potentially critical for maintaining normal cellular metabolism under conditions of impaired acyl-CoA use and that exposure of humans and other mammals to ethanol effects leads to impairment of mitochondrial function. The aim of the present study was to evaluate the role of ethanol on urinary excretion of short-chain organic acids and endogenous carnitines in rats. The data reported show that ethanol significantly increases urinary excretion of propionate, methylmalonate, as well as free acetate, butyrate, pyruvate, lactate, and beta-hydroxybutyrate. Furthermore, the increased formation of propionate and methylmalonate was dependent on the dose of ethanol; did not require the metabolism of ethanol, as was shown in experiments with pyrazole treatment of ethanol rats; and appears to be mediated by beta-adrenergic mechanisms because propranolol almost completely suppresses propionate accumulation. Alcohol administration also increased excretion of specific acyl-carnitines, corresponding to the accumulating acyl groups, whereas excretion of free carnitine was significantly reduced, with respect to control values. The data presented indicate that the short-term ethanol administration is associated with increased excretion of selected organic acids. This study suggests that endogenous carnitine pool might play a role against the deleterious effects of accumulating short-chain organic acids.
Calabrese
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Biochemistry, Faculty of Medicine, University of Catania, Italy. calabres@mbox.unict.it
Rizza
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V
D000144:Acids, Acyclic / Q000652:urine*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D002331:Carnitine / Q000652:urine*; D002492:Central Nervous System Depressants / Q000008:administration & dosage*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000431:Ethanol / Q000008:administration & dosage*; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine*; D011422:Propionates / Q000652:urine*; D011433:Propranolol / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats
D000144:Acids, Acyclic; D000319:Adrenergic beta-Antagonists; D002492:Central Nervous System Depressants; D004791:Enzyme Inhibitors; D011422:Propionates; D011720:Pyrazoles; D000431:Ethanol; C031280:pyrazole; D008764:Methylmalonic Acid; D011433:Propranolol; C029658:propionic acid; D002331:Carnitine