Mitochondrial ALDH polymorphism affects ethanol-derived acetate disposition in Wistar rats.
We studied the relationship between polymorphism of aldehyde dehydrogenase (ALDH) and ethanol and acetate kinetics in male Wistar rats. Blood ethanol and acetate concentration time curves after intravenous bolus administration of 1 g/kg of ethanol were estimated by moment analysis. ALDH isozymes in hepatic subcellular fractions were detected by isoelectric focusing (IEF). Blood acetate profiles were divided into two patterns: one-peak type and two-peak type. IEF studies on ALDH isozymes in subcellular fractions showed polymorphism of cytosolic and mitochondrial ALDHs. Polymorphism patterns of ALDH2 corresponded with patterns of blood acetate profiles. Significant differences in mean residence time of acetate and the ratio of area under curves (AUCs) of acetate to ethanol (AUCacetate/AUCEtOH) occurred between different IEF patterns of mitochondrial low K(m) ALDH (ALDH2). Therefore, it was clarified that ALDH2 polymorphism affects ethanol-derived acetate disposition in Wistar rats. Similarity of AUC values of acetate considered, these observations suggest that ALDH2 polymorphism results in change of effects of acetate and acetate-generated adenosine on the central nervous system and other organs during chronic ethanol consumption.
Matsumoto
H
H
Department of Legal Medicine, Kyoto University Faculty of Medicine, Japan.
Matsubayashi
K
K
Fukui
Y
Y
D000079:Acetaldehyde / Q000493:pharmacokinetics*; D000444:Aldehyde Dehydrogenase / Q000235:genetics* / Q000502:physiology; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000818:Animals; D003600:Cytosol / Q000201:enzymology; D000431:Ethanol / Q000493:pharmacokinetics*; D007525:Isoelectric Focusing; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology / Q000235:genetics*; D011110:Polymorphism, Genetic; D051381:Rats; D017208:Rats, Wistar
D000431:Ethanol; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde