アルデヒド脱水素酵素2（ALDH2）の構造・機能の基礎と<i>ALDH2</i>遺伝子多型の重要性

Abstract

Human aldehyde dehydrogenase 2 (ALDH2) is a 56 kDa mitochondrial protein that forms homodimers through hydrogen bonding interactions between the Glu487 and Arg475 residues of two ALDH2 proteins. Two ALDH2 homodimers can interact to form an ALDH2 tetramer. ALDH2 is widely distributed throughout the organs of the body. In addition to its dehydrogenase activity, ALDH2 also exhibits esterase and reductase activities, with the main substrates for these three activities being aldehydes, 4-nitrophenyl acetate and nitroglycerin, respectively. ALDH2 can be readily inhibited by a wide variety of endogenous and exogenous chemicals, but the induction or activation of this enzyme remains unlikely. The polymorphism of ALDH2 to the corresponding ALDH2*2 variant results in a severe deficiency in ALDH2 activity, and this particular polymorphism is prevalent among people of Mongoloid descent. It seems reasonable to expect that people with the ALDH2*2 variant would be more vulnerable to stress and diseases because ALDH2 defends the human body against toxic aldehydes. However, it has been suggested that people with the ALDH2*2 variant are protected by alternative stress-defending systems. The ALDH2*2 variant has been reported to be associated with many different kinds of diseases, although the mechanisms underlying these associations have not yet been elucidated. ALDH2 polymorphism has a significant impact on human health; further studies are therefore required to determine the practical implications of this polymorphism in the fields of preventive and clinical medicine.