Aldehyde dehydrogenase (ALDH) 2 associates with oxidation of methoxyacetaldehyde; in vitro analysis with liver subcellular fraction derived from human and Aldh2 gene targeting mouse

A principal pathway of 2-methoxyethanol (ME) metabolism is to the toxic oxi dative product, methoxyacetaldehyde (MALD). To assess the role of aldehyde dehydrogenase (ALDH) in MALD metabolism, in vitro MALD oxidation was examin ed with liver subcellular fractions from Japanese subjects who carried thre e different ALDH2 genotypes and Aldh2 knockout mice, which were generated i n this study. The activity was distributed in mitochondrial fractions of AL DH2*11*1 and wild type (Aldh2+/+) mice but not ALDH2*11*2, *2/*2 subjects o r Aldh2 homozygous mutant (Aldh2-/-) mice. These data suggest that ALDH2 is a key enzyme for MALD oxidation and ME susceptibility may be influenced by the ALDH2 genotype. (C) 2000 Federation of European Biochemical Societies, Published by Elsevier Science B.V. All rights reserved.