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 oxidative product, methoxyacetaldehyde (MALD). To assess the role of aldehyde dehydrogenase (ALDH) in MALD metabolism, in vitro MALD oxidation was examined with liver subcellular fractions from Japanese subjects who carried three different ALDH2 genotypes and Aldh2 knockout mice, which were generated in this study. The activity was distributed in mitochondrial fractions of ALDH2*1/*1 and wild type (Aldh2+/+) mice but not ALDH2*1/*2, *2/*2 subjects or 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.
Department of Environmental Health, University of Occupational and Environmental Health, Kitakyushu, Japan.
K
K
Kitagawa
T
T
Kawamoto
N
N
Kunugita
T
T
Tsukiyama
K
K
Okamoto
A
A
Yoshida
K
K
Nakayama
K
K
Nakayama
D000079:Acetaldehyde / Q000031:analogs & derivatives* / Q000378:metabolism; D000444:Aldehyde Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010084:Oxidation-Reduction; D011110:Polymorphism, Genetic; D013347:Subcellular Fractions / Q000201:enzymology / Q000378:metabolism
D017931:DNA Primers; C049826:2-methoxyacetaldehyde; C096127:ALDH2 protein, human; D000444:Aldehyde Dehydrogenase; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D000079:Acetaldehyde