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ALDH Overview


Aldehyde Dehydrogenase (ALDH) Gene Superfamily
ALDH Naming Conventions Prior to 1998
ALDH Nomenclature System

Aldehyde Dehydrogenase (ALDH) Gene Superfamily

(Last modified 2007-4-19)

The ALDH gene superfamily (E.C. 1.2.1.3) encodes "a cluster of evolutionarily related sequences" (Dayhoff, 1976), with pyridine-nucleotide-dependent oxidoreductase activity. A gene superfamily consists of homologous gene families, which are clusters of genes from different genomes that include both orthologs and paralogs (Tatusov, et al., 1997). Orthologs are genes in different species that evolved from a common ancestor by separation, whereas paralog genes are products of gene duplication events within the same genome.

 

The ALDH superfamily includes NAD(P)+-dependent enzymes catalyzing the oxidation of a wide spectrum of aliphatic and aromatic aldehydic substrates generated from various endogenous and exogenous precursors to their corresponding carboxylic acids. Endogenous aldehydes are formed during metabolism of alcohols, amino acids, biogenic amines, vitamins, steroids and lipids. Exogenous aldehydes are often generated from the metabolism of a number of drugs and environmental agents. Although most ALDHs display broad specificities, oxidizing a variety of both aliphatic and aromatic aldehydes, other forms possess narrower substrate preferences. Prior to the induction of the ALDH nomenclature system in 1998, ALDH isozymes were broadly distinguished based on physicochemical properties, enzyme properties, tissue/subcellular distributions and substrate specificities as described below.

 

ALDH Naming Conventions Prior to 1998

Semi-Aldehyde Dehydrogenases

  • Semialdehyde dehydrogenase (E.C. 1.2.1.32)
  • Escherichia coli (E.C. 1.2.1.16) and mammalian (E.C. 1.2.1.24) succinate-semialdehyde dehydrogenase
  • Glutamate semialdehyde dehydrogenase (E.C. 1.2.1.41)
  • Aspartate semialdehyde dehydrogenase (E.C. 1.2.1.11)
  • 2-amino-adipate-6-semialdehyde dehydrogenase (E.C. 1.2.1.31)
  • Metylmalonate-semialdehyde dehydrogenase (E.C. 1.2.1.27)

 

Non-specific Aldehyde Dehydrogenases

  • Class 1
  • Class 2
  • Class 3

 

Other Aldehyde Dehydrogenases

  • Betaine dehydrogenase (E.C. 1.2.1.8)
  • Non-phosphorylating glyceraldehyde 3-phosphate dehydrogenase (E.C. 1.2.1.9)
  • Phenylacetaldehyde dehydrogenase (E.C. 1.2.1.39)
  • Methylmalonate-semialdehyde dehydrogenase (E.C. 1.2.1.27)

 

Aldehyde Dehydrogenase-like Proteins

  • 10-formyltetrahydrofolate dehydrogenase (E.C. 1.5.1.6)
  • D1-pyrroline-5-carboxylate dehydrogenase (E.C. 1.5.1.12)
  • Antiquitin
  • Human 56-kDa androgen-binding protein
  • Crystallins

 

ALDH Nomenclature System

A standardized gene nomenclature system based on divergent evolution was established in 1998. This nomenclature system replaced the broad categorization based on substrate specificity as presented above and was approved by the participants of the Ninth International Workshops on Enzymology and Molecular Biology of Carbonyl Metabolism (June 1998).

Briefly, the current nomenclature system functions as outlined below. For naming each gene, the root symbol ALDH, is followed by the Arabic number representing the Family, and when needed, a letter which designates the Subfamily. The Arabic number which follows the letter denotes the individual Gene within the subfamily. An ALDH protein from one gene family is defined as having <40% amino-acid identity to that from another family. Two members of the same subfamily exhibit approximately >60% amino-acid identity. All letters are capitalized for all mammals except the mouse and the fruit fly ( e.g. mus musculous / drosophila melangaster Aldh1a1). The gene for the mouse and fruit fly is italicized, whereas the corresponding cDNA, mRNA, protein or enzyme activity for all species including the mouse and fruit fly is written with upper-case letters and without italics (e.g. human, mouse or Drosophila ALDH1A1 cDNA, mRNA, or activity).

 

The explosion in molecular biology during the past decade, along with the release of complete or partially complete genome sequences of various species, has resulted in the discovery of many unexpected additional genes in almost every gene superfamily. As of April 2007, 19 genes in mouse and rat, and 18 in human whose protein products contain the ALDH "signature sequence" (Hempel et al., 1993), and thus, are regarded as members of the ALDH superfamily have been identified.

 

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