ALDH GENE SPERFAMILY: An Introduction

Last update August 22, 1999

• Gene superfamily is defined as "a cluster of evolutionarily related sequences" (Dayhoff, 1976), and 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.
• ALDH superfamily includes NAD(P)⁺-dependent enzymes that have similar primary structures and oxidize a wide spectrum of endogenous and exogenous aldehydes (Lindahl, 1992). Several ALDHs display broad specificities, oxidizing a variety of both aliphatic and aromatic aldehydes, whereas other forms possess narrower substrate preferences. ALDH enzymes are broadly categorized, based on substrate specificities, as:
  

  Semialdehyde dehydrogenases	Nonspecific ALDHs	Other ALDHs	ALDH-like proteins
  Semialdehyde dehydrogenase (E.C. 1.2.1.32) Escherichia coli (EC 1.2.1.16) and mammalian (EC 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)	Known as Class 1 Class 2 Class 3	Betaine dehydrogenase (E.C. 1.2.1.8) Non phosphorylating glyceraldehyde 3-phosphate dehydrogenase (E.C. 1.2.1.9) Phenylacetaldehyde dehydrogenase (EC 1.2.1.39) Metylmalonate-semialdehyde dehydrogenase (E.C. 1.2.1.27)	10-formyltetrahydrofolate dehydrogenase (E.C. 1.5.1.6) D1-pyrroline-5-carboxylate dehydrogenase (EC 1.5.1.12) Antiquitin Human 56-kDa androgen-binding protein Crystallins

• 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. At latest count (June 1998), in bacteria, plants, yeast, and animals there are 164 distinct cDNAs/genes whose protein products contain the ALDH "signature sequence" (Hempel et al., 1993), and thus, are regarded as members of the ALDH superfamily. These sequences include 4 archaebacterial genes, 71 eubacterial, and 89 eukaryotic sequences (Ziegler & Vasiliou, 1999). 

Summary of ALDH Gene Superfamily

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E-mail questions or comments to: vasilis.casiliou@ucdenver.edu