Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily

Expert Opin Drug Metab Toxicol. 2008 Jun;4(6):697-720. doi: 10.1517/17425255.4.6.697.

Abstract

Background: Aldehydes are highly reactive molecules. While several non-P450 enzyme systems participate in their metabolism, one of the most important is the aldehyde dehydrogenase (ALDH) superfamily, composed of NAD(P)+-dependent enzymes that catalyze aldehyde oxidation.

Objective: This article presents a review of what is currently known about each member of the human ALDH superfamily including the pathophysiological significance of these enzymes.

Methods: Relevant literature involving all members of the human ALDH family was extensively reviewed, with the primary focus on recent and novel findings.

Conclusion: To date, 19 ALDH genes have been identified in the human genome and mutations in these genes and subsequent inborn errors in aldehyde metabolism are the molecular basis of several diseases, including Sjögren-Larsson syndrome, type II hyperprolinemia, gamma-hydroxybutyric aciduria and pyridoxine-dependent seizures. ALDH enzymes also play important roles in embryogenesis and development, neurotransmission, oxidative stress and cancer. Finally, ALDH enzymes display multiple catalytic and non-catalytic functions including ester hydrolysis, antioxidant properties, xenobiotic bioactivation and UV light absorption.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aldehyde Dehydrogenase / genetics
  • Aldehyde Dehydrogenase / metabolism*
  • Aldehydes / metabolism*
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Isoenzymes
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism
  • Mutation
  • Oxidation-Reduction
  • Substrate Specificity

Substances

  • Aldehydes
  • Isoenzymes
  • Aldehyde Dehydrogenase