Polymorphism of aldehyde dehydrogenase and alcohol sensitivity.
The metabolism of acetaldehyde has received considerable attention in the past years owing to its acute and chronic toxic effects in humans. Aldehyde dehydrogenase (ALDH) catalyzes the oxidation of acetaldehyde in liver and other organs. Two major isozymes of hepatic ALDH (ALDH I or E2 and ALDH II or E1), which differ in their structural and functional properties, have been characterized in humans. The ALDH I with a low Km for acetaldehyde is predominantly of mitochondrial origin and ALDH II which has a relatively higher Km is of cytosolic origin. An inherited deficiency of ALDH I isozyme has been found among Japanese and Chinese which is primarily responsible for producing acute alcohol sensitivity symptoms (flushing response) after drinking mild doses of alcohol. Biochemical, immunochemical and molecular genetics data indicate a structural mutation in the ALDH I isozyme gene responsible for the loss in catalytic activity. Population genetic studies indicate a wide prevalence of this ALDH polymorphism among individuals of Mongoloid race. Flushing response to alcohol shows familial resemblances and preliminary family data from Japan, China and Korea hint to an autosomal codominant inheritance for ALDH I isozyme deficiency. The ALDH polymorphism is apparently responsible for the low incidence of alcoholism in Japanese, Chinese and Koreans. Alcohol-induced sensitivity due to ALDH isozyme deficiency may act as an inhibitory factor against excessive alcohol drinking thereby imparting a protection against alcoholism.
D000428:Alcohol Drinking; D000437:Alcoholism / Q000201:enzymology / Q000235:genetics; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D044466:Asian People; D005483:Flushing / Q000201:enzymology / Q000235:genetics; D006801:Humans; D005779:Immunodiffusion; D007123:Immunoelectrophoresis, Two-Dimensional; D007525:Isoelectric Focusing; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D044468:Native Hawaiian or Pacific Islander; D010375:Pedigree; D011110:Polymorphism, Genetic; D044465:White People
D007527:Isoenzymes; D000444:Aldehyde Dehydrogenase