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Related Experiment Videos

Alcohol and aldehyde dehydrogenase.

T Ehrig1, W F Bosron, T K Li

  • 1Department of Biochemistry, Indiana University School of Medicine, Indianapolis 46202.

Alcohol and Alcoholism (Oxford, Oxfordshire)
|January 1, 1990
PubMed
Summary

Genetic variations in alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) enzymes affect alcohol metabolism rates. These enzyme differences influence how individuals process alcohol and acetaldehyde, impacting predisposition to excessive alcohol consumption.

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Area of Science:

  • Biochemistry
  • Human Genetics
  • Pharmacology

Background:

  • Ethanol metabolism in humans primarily involves liver alcohol dehydrogenases (ADH) and aldehyde dehydrogenases (ALDH).
  • Genetic polymorphisms in ADH and ALDH enzymes lead to variations in their kinetic properties.
  • These variations can significantly affect an individual's capacity to metabolize alcohol and its toxic byproduct, acetaldehyde.

Purpose of the Study:

  • To investigate the impact of genetic polymorphisms in ADH and ALDH enzymes on human alcohol metabolism.
  • To correlate variations in enzyme activity with differences in alcohol and acetaldehyde metabolic rates.
  • To explore the role of these enzymatic differences in the genetic predisposition to excessive alcohol intake.

Main Methods:

  • Analysis of steady-state kinetic constants (Km and Vmax) for relevant ADH isoenzymes.

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  • Examination of the functional consequences of ALDH2 isoenzyme polymorphisms, including the inactive 'Oriental' variant.
  • Correlation of observed enzymatic differences with interindividual variations in alcohol metabolism.
  • Main Results:

    • ADH isoenzymes exhibit a range of Km-values for ethanol from 49 microM to 36 microM and Vmax-values from 0.6 to 10 U/mg.
    • An inactive ALDH2 variant impairs acetaldehyde metabolizing capacity.
    • Significant differences in ethanol and acetaldehyde metabolic activities were observed between allelic enzyme forms.

    Conclusions:

    • Variations in ADH and ALDH enzyme activity due to genetic polymorphisms contribute to the wide range of alcohol metabolism rates in humans.
    • Specific enzyme variants, like the inactive ALDH2 form, directly impair acetaldehyde breakdown.
    • Interindividual differences in enzyme profiles may underlie a genetically determined susceptibility to excessive alcohol consumption.