Role of Aldehyde Dehydrogenases in Endogenous and Xenobiotic Metabolism

Chem Biol Interact. 2000 Dec 1;129(1-2):1-19. doi: 10.1016/s0009-2797(00)00211-8.

Abstract

Aldehydes are highly reactive molecules that are intermediates or products involved in a broad spectrum of physiologic, biologic and pharmacologic processes. Aldehydes are generated from chemically diverse endogenous and exogenous precursors and aldehyde-mediated effects vary from homeostatic and therapeutic to cytotoxic, and genotoxic. One of the most important pathways for aldehyde metabolism is their oxidation to carboxylic acids by aldehyde dehydrogenases (ALDHs). Oxidation of the carbonyl functional group is considered a general detoxification process in that polymorphisms of several human ALDHs are associated a disease phenotypes or pathophysiologies. However, a number of ALDH-mediated oxidation form products that are known to possess significant biologic, therapeutic and/or toxic activities. These include the retinoic acid, an important element for vertebrate development, gamma-aminobutyric acid (GABA), an important neurotransmitter, and trichloroacetic acid, a potential toxicant. This review summarizes the ALDHs with an emphasis on catalytic properties and xenobiotic substrates of these enzymes.

Publication types

  • Research Support, U.S. Gov't, P.H.S.
  • Review

MeSH terms

  • Aldehyde Dehydrogenase / classification
  • Aldehyde Dehydrogenase / genetics*
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehydes / metabolism
  • Animals
  • Carboxylic Acids / metabolism
  • Humans
  • Oxidation-Reduction
  • Vertebrates
  • Xenobiotics / pharmacokinetics*
  • gamma-Aminobutyric Acid / metabolism

Substances

  • Aldehydes
  • Carboxylic Acids
  • Xenobiotics
  • gamma-Aminobutyric Acid
  • Aldehyde Dehydrogenase