Aldehyde dehydrogenase 2 (ALDH2) polymorphism and metabolism of aldehydes

摘要

It is well known that many Asian people, especially half of Japanese people, genetically lack Aldehyde dehydrogenase (ALDH) 2 which is an isozyme of ALDH family. However, the influence of the ALDH2 polymorphism on the metabolite production of the chemicals which undergo ALDH metabolism is not clear, even though the metabolites are used as exposure markers. We investigated the metabolism of propionaldehyde and dodecyl aldehyde in Aldh2 knockout mice, which have been developed in our laboratory. The ALDH activity toward propionaldehyde was measured by production of NADH. At low concentration (50mM), ALDH activity of mitochondrial fraction was more than 10 times lower in the Aldh2 knockout mouse than in the control mouse. Enzymatic activity was also studied by PAGE-isoelectric focusing (IEF) and zymogram. When propionaldehyde is used as substrate, an activity band of dehydrogenation was found at pi 6.0 only in the control mouse liver fraction, but not in the Aldh2 knockout mouse liver fraction. This band was reacted with anti-ALDH2 antibody by the Western blot analysis. When dodecylaldehyde was used as substrate, the difference between the knockout mouse and control mouse was not significant in NADH production or zymogram. This result suggests the ALDH2 polymorphism affects metabolism of some aldehydes.