Rationale for Alcoholism Treatment Based on Inhibition of Aldehyde Dehydrogenase

  • H. T. Nagasawa
  • C.-H. Kwon
  • J. A. Elberling
  • M. J. C. Lee
  • E. G. DeMaster
  • F. N. Shirota
  • D. J. W. Goon
Conference paper

Abstract

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.

Keywords

Hydrolysis Aldehyde Lysine Cyanide Catalase 

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Copyright information

© Springer-Verlag New York, Inc. 1992

Authors and Affiliations

  • H. T. Nagasawa
    • 1
    • 2
  • C.-H. Kwon
    • 2
  • J. A. Elberling
    • 1
  • M. J. C. Lee
    • 2
  • E. G. DeMaster
    • 1
  • F. N. Shirota
    • 1
  • D. J. W. Goon
    • 2
  1. 1.Medical Research LaboratoriesV. A. Medical CenterUSA
  2. 2.University of MinnesotaMinneapolisUSA

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