The enzyme encoded by this gene belongs to the aldehyde dehydrogenase family of enzymes that catalyze the chemical transformation from acetaldehyde to acetic acid. Aldehyde dehydrogenase is the second enzyme of the major oxidative pathway of alcohol metabolism.
Two major liver isoforms of this enzyme, cytosolic and mitochondrial, can be distinguished by their electrophoretic mobilities, kinetic properties, and subcellular localizations. The ALDH2 gene encodes a mitochondrial isoform, which has a low Km for acetaldehydes, and is localized in mitochondrial matrix; in contrast the ALDH1 gene codes for the cytosolic isoform.
Most Europeans have two major isozymes, while approximately 50% of Northeast Asians have one normal copy of the ALDH2 gene and one mutant copy that encodes an inactive mitochondrial isoenzyme. A remarkably higher frequency of acute alcohol intoxication among Northeast Asians than among Europeans has been repeatedly shown to be related to the very much reduced activity of the mutant ALDH2-2 isoenzyme. There has been a steady increase over the past 10 years in the number of Japanese alcoholics who manage to overcome their genetically determined aversion to alcoholism from the dominant effects of an ALDH2-2 mutation. This trend demonstrates that, even among those least likely to succumb to alcoholism, there are social pressures to drink.
An activator of ALDH2 enzymatic activity, Alda-1 (N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide), has been shown to reduce ischemia-induced cardiac damage caused by myocardial infarction.
^Lee KH, Kim HS, Jeong HS, Lee YS (October 2002). "Chaperonin GroESL mediates the protein folding of human liver mitochondrial aldehyde dehydrogenase in Escherichia coli". Biochem. Biophys. Res. Commun.298 (2): 216–24. doi:10.1016/S0006-291X(02)02423-3. PMID12387818.CS1 maint: Date and year (link)
Chao YC, Liou SR, Tsai SF, Yin SJ (1993). "Dominance of the mutant ALDH2(2) allele in the expression of human stomach aldehyde dehydrogenase-2 activity". Proc. Natl. Sci. Counc. Repub. China B17 (3): 98–102. PMID8290656.
Braun T, Bober E, Singh S, Agarwal DP, Goedde HW (1987). "Evidence for a signal peptide at the amino-terminal end of human mitochondrial aldehyde dehydrogenase". FEBS Lett.215 (2): 233–6. doi:10.1016/0014-5793(87)80152-7. PMID3582651.
Hempel J, Höög JO, Jörnvall H (1987). "Mitochondrial aldehyde dehydrogenase. Homology of putative targeting sequence to that of carbamyl phosphate synthetase I revealed by correlation of cDNA and protein data". FEBS Lett.222 (1): 95–8. doi:10.1016/0014-5793(87)80198-9. PMID3653404.Vancouver style error (help)
Hempel J, Kaiser R, Jörnvall H (1985). "Mitochondrial aldehyde dehydrogenase from human liver. Primary structure, differences in relation to the cytosolic enzyme, and functional correlations". Eur. J. Biochem.153 (1): 13–28. doi:10.1111/j.1432-1033.1985.tb09260.x. PMID4065146.Vancouver style error (help)
Novoradovsky A, Tsai SJ, Goldfarb L, Peterson R, Long JC, Goldman D (1995). "Mitochondrial aldehyde dehydrogenase polymorphism in Asian and American Indian populations: detection of new ALDH2 alleles". Alcohol. Clin. Exp. Res.19 (5): 1105–10. doi:10.1111/j.1530-0277.1995.tb01587.x. PMID8561277.