Rationale for Alcoholism Treatment Based on Inhibition of Aldehyde Dehydrogenase
It has been long recognized that certain individuals, particularly of Oriental origin, present a pronounced facial flush on consumption of only modest quantities of alcoholic beverages, thereby sustaining a natural aversion to alcohol (ethanol). These individuals lack a functional low Km hepatic mitochondrial aldehyde dehydrogenase (A1DH2) that metabolizes acetaldehyde, the first product of ethanol metabolism (1). This inborn trait observed in 40–50% of Orientals has been shown to be due to a genetic defect manifested by a point mutation on A1DH2, with the amino acid lysine replacing a glutamate residue near the C-terminal end of the enzyme (2). The consumption of ethanol by such individuals gives rise to elevated blood acetaldehyde levels and a flushing reaction reminiscent of the disulfiram-ethanol reaction (3), leading to alcohol avoidance.
KeywordsAldehyde Dehydrogenase Alcoholic Liver Disease Amino Acid Lysine Natural Aversion AlDH Isozyme
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