The Big Book of Aldehyde Dehydrogenase Sequences

An Overview of the Extended Family
  • John Perozich
  • Hugh Nicholas
  • Ronald Lindahl
  • John Hempel
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 463)


Traditionally, research on aldehyde dehydrogenases (ALDHs, EC 1.2.1) has focused on three groups: class 1, 2, and 3 ALDHs. Class 1 and 2 ALDHs are very closely related homotetramers and both participate in ethanol metabolism, though class 1 ALDHs can oxidize wide range of metabolites, including retinal (reviewed Lindahl, 1982; Yoshida et al., 1). Class 3 ALDHs appear at first glance to be highly divergent from the other 2 classes. Class 3 ALDHs share only about 25% sequence identity with class 1 and 2 ALDHs and are homodimers. However, in main-chain folding, the structures of the class 2 and 3 monomers are nearly identical (Hempel et al., 1999)


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  1. Boch, J., Kempf, B., Schmid, R. and Bremer, E. (1996) Synthesis of the osmoprotectant glycine betaine in Bacillus subtilis: Characterization of the gbsAB genes. J Bacteriol 178, 5121–5129.PubMedGoogle Scholar
  2. Chambliss, K.L., Caudle, D.L., Hinson, D.D., Moomaw, C.R., Slaughter, CA., Jakobs, C. and Gibson, K.M. (1995) Molecular cloning of the mature NAD(+)-dependent succinic semialdehyde dehydrogenase from rat and human. cDNA isolation, evolutionary homology, and tissue expression. J Biol Chem 270, 461–467.PubMedCrossRefGoogle Scholar
  3. Cook, R.J., Lloyd, R.S. and Wagner, C. (1991) Isolation and characterization of cDNA clones for rat liver 10-for-myltetrahydrofolate dehydrogenase. J Biol Chem 266, 4965–4973.PubMedGoogle Scholar
  4. Cooper, D.L. and Baptist, E.W. (1991) Degenerate oligonucleotide-directed PCR cloning of the BCP54/A1DH 3 cDNA. PCR Meth Appl 1, 57–62.CrossRefGoogle Scholar
  5. De Laurenzi, V., Rogers, G.R., Hamrock, D.J., Marekov, L.N., Steinert, P.M., Compton, J.G., Markova, N. and Rizzo, W.B. (1996) Sjögren-Larsson Syndrome is caused by mutations in the fatty aldehyde dehydrogenase gene. Nature Genet 12, 52–57.PubMedCrossRefGoogle Scholar
  6. Dockham, P.A., Lee, M.-O. and Sladek, N.E. (1992) Identification of human AlDHs that catalyze the oxidation of aldophosphamide and retinaldehyde. Biochem Pharmacol 43, 2453–2469.PubMedCrossRefGoogle Scholar
  7. Domeyer, B.E. and Sladek, N.E. (1980) Metabolism of 4-OH-cyclophosphamide and aldophosphamide in vitro. Biochem Pharmacol 29, 2903–2912.PubMedCrossRefGoogle Scholar
  8. Graham, C, Hodin, J. and Wistow, G. (1996) A retinaldehyde dehydrogenase as a structural protein in a mammalian eye lens. Gene recruitment of eta-crystallin. J Biol Chem 271, 15623–15628.PubMedCrossRefGoogle Scholar
  9. Guerrero, F.D., Jones, J.T. and Mullet, J.E. (1990) Turgor-responsive gene transcription and RNA levels increase rapidly when pea shoots are wilted. Sequence and expression of three inducible genes. Plant Mol Biol 15, 11–26.PubMedCrossRefGoogle Scholar
  10. Habenicht, A., Hellman, U. and Cerff, R. (1994) Non-phosphorylating GAPDH of higher plants is a member of the aldehyde dehydrogenase family with no sequence homology to phosphorylating GAPDH. J Mol Biol 237, 165–171.PubMedCrossRefGoogle Scholar
  11. Harada, S., Agarwal, D.P. and Goedde, H.W. (1981) A1DH deficiency as cause of facial flushing reaction to alcohol in Japanese. Lancet 11, 982.CrossRefGoogle Scholar
  12. Hempel, J., Nicholas, H. and Lindahl R. (1993) Aldehyde dehydrogenases: Widespread structural and functional diversity within a shared framework. Prot Sci 2, 1890–1900.CrossRefGoogle Scholar
  13. Hempel, J., Perozich, J., Chapman, T., Rose, J., Liu, Z.-J., Boesch, J.S., Wang, B.-C. and Lindahl, R. (1999) Aldehyde dehydrogenase catalytic mechanism: A proposal. Adv Exp Med Biol(this meeting).Google Scholar
  14. Hu, C.A., Lin, W.W. and Valle, D. (1996) Cloning, characterization, and expression of cDNAs encoding human delta 1-pyrroline-5-carboxylate dehydrogenase. J Biol Chem 271, 9795–9800.PubMedCrossRefGoogle Scholar
  15. Inoue, J., Shaw, J.P., Rekik, M. and Harayama, S. (1995) Overlapping substrate specificities of benzaldehyde dehydrogenase (the xylC gene product) and 2-hydroxymuconic SADH (the xylG gene product) encoded by TOL plasmid pWWO of Pseudomonas putida. J Bacteriol 177, 1196–1201.PubMedGoogle Scholar
  16. Jakobs, C., Jaeken, J. and Gibson, K.M. (1993) Inherited disorders of GABA metabolism. J Inher Metab 16, 704–715.CrossRefGoogle Scholar
  17. James, P.F. and Zoeller, R.A. (1997) Isolation of animal cell mutants defective in long-chain fatty acid aldehyde dehydrogenase. Sensitivity fatty aldehydes and Schiff’s base modification of phospholipids: Implications for Sjögren-Larsson Syndrome. J Biol Chem 272, 23532–23539.PubMedCrossRefGoogle Scholar
  18. Kedishvili, N.Y., Popov, K.M., Rougraff, P.M., Zhao, Y., Crabb, D.W. and Harris, R.A. (1992) CoA-dependent methylmalonate semialdehyde dehydrogenase, a unique member of the aldehyde dehydrogenase superfa-mily. J Biol Chem 267, 19724–19729.PubMedGoogle Scholar
  19. King, C.T. and Holmes, R.S. (1997) Human corneal and lens aldehyde dehydrogenases: Purification and properties of human lens ALDH1 and differential expression as major soluble proteins in human lens (ALDH1) and cornea (ALDH3). Adv Exp Med Biol 414, 19–27.PubMedCrossRefGoogle Scholar
  20. Kitson, T.M. (1977) The disulfiram-ethanol reaction: A review. J Stud Alcohol 38, 96–113.PubMedGoogle Scholar
  21. Krupenko, S.A., Wagner, C. and Cook, R.J. (1997) Expression, purification, and properties of the aldehyde dehydrogenase homologous carboxyl-terminal domain of rat 10-formyltetrahydrofolate dehydrogenase. J Biol Chem 272, 10266–10272.PubMedCrossRefGoogle Scholar
  22. Lee, M.-O., Manthey, C.L. and Sladek, N.E. (1991) Identification of mouse liver AlDHs that catalyze the oxidation of retinaldehyde to retinoic acid. Biochem Pharmacol 42, 1279–1285.PubMedCrossRefGoogle Scholar
  23. Lindahl, R. (1992) Aldehyde dehydrogenases and their role in carcinogenesis. Crit Rev Biochem Mol Biol 27, 283–335.PubMedCrossRefGoogle Scholar
  24. Lindahl, R. and Petersen, D.R. (1991) Lipid aldehyde oxidation as a physiological role for class 3 A1DH. Biochem Google Scholar
  25. Ling, M., Allen, S.W. and Wood, J.M. (1994) Sequence analysis identifies the proline dehydrogenase and delta-1-pyrroline-5-carboxylate dehydrogenase domains of the multifunctional Escherichia coli PutA protein. J Mol Biol 243, 950–956.PubMedCrossRefGoogle Scholar
  26. Liu, Z.-J., Sun, Y.-J., Rose, J., Chung, Y.-J., Hsiao, C.-D., Chang, W.-R., Kuo, I., Perozich, J., Lindahl, R., Hempel, J. and Wang, B.-C. (1997) The first structure of an aldehyde dehydrogenase reveals novel interactions between NAD and the Rossmann fold. Nature Struct Biol 4, 317–326.PubMedCrossRefGoogle Scholar
  27. Moore, S.A., Baker, H.M., Blythe, T., Kitson, K.E., Kitson, T.M. and Baker, E.N. (1999) Structure of a class 1 mammalian aldehdye dehydrogenase at 2.35Ïresolution. Adv Exp Med Biol(this meeting).Google Scholar
  28. Ni, L., Sheikh, S. and Weiner, H. (1997) Involvement of glutamate 399 and lysine 192 in the mechanism of human liver mitochondrial aldehyde dehydrogenase. J Biol Chem 272, 18823–18826.PubMedCrossRefGoogle Scholar
  29. Nordlund, I. and Shingler, V. (1990) Nucleotide sequences of the meta-cleavage pathway enzymes 2-hydroxymu-conic semialdehyde dehydrogenase and 2-hydroxymuconic semialdehyde hydrolase from Pseudomonas CF600. Biochim Biophys Ada 1049, 227–230.CrossRefGoogle Scholar
  30. Op den Camp, R.G. and Kuhlemeier, C. (1997) Aldehyde dehydrogenase in tobacco pollen. Plant Mol Biol 35, 355–365.CrossRefGoogle Scholar
  31. Perozich, J., Nicholas, H., Wang, B.-C, Lindahl, R. and Hempel, J. (1998) Relationships within the aldehyde dehydrogenase extended family. Prot Sci(submitted).Google Scholar
  32. Phang, J.M., Yeh, G.C. and Scriver, C.R. (1995) Disorders of proline and hydroxyproline metabolism. In: Scriver, C.R., Beaudet, A.L., Sly, W.S. and Valle, D., eds. The Metabolic and Molecular Bases of Inherited Disease, 7th edition. New York: McGraw-Hill, pp 1107–1124.Google Scholar
  33. Pietruszko, R., Kikonyogo, A., Chern, M.-K. and Izaguirre, G. (1997) Human aldehyde dehydrogenase E3: Further characterization. Adv Exp Med Biol 414, 243–252.PubMedCrossRefGoogle Scholar
  34. Priefert, H., Rabenhorst, J., Steinbuchel, A. (1997) Molecular characterization of genes of Pseudomonas sp. strain HR199 involved in bioconversion of vanillin to protocatechuate. J Bacteriol 179, 2595–2607.PubMedGoogle Scholar
  35. Rizzo, W.B. (1993) Sjögren-Larsson syndrome. Sem Dermatol 12, 210–218.Google Scholar
  36. Steinmetz, C.G., Xie, P., Weiner, H. and Hurley, T.D. (1997) Structure of mitochondrial aldehyde dehydrogenase: the genetic component of ethanol aversion. Structure 15, 701–711.CrossRefGoogle Scholar
  37. Straub, P.R., Reynolds, P.H., Althomsons, S., Mett, V., Zhu, Y, Shearer, G. and Kohl, D.H. (1996) Isolation, DNA sequence analysis, and mutagenesis of a proline dehydrogenase gene (putA) from Bradyrhizobium japoni-cum. Appl Environ Microbiol 62, 221–229PubMedGoogle Scholar
  38. Stroeher, V.L., Boothe, J.G. and Good, A.G. (1995) Molecular cloning and expression of a turgor-responsive gene in Brassica napus. Plant Mol Biol 27, 541–551.PubMedCrossRefGoogle Scholar
  39. Wang, X.-P. and Weiner, H. (1995) Involvement of glutamate 268 in the active site of human liver mitochondrial (class 2) aldehyde dehydrogenase as probed by site-directed mutagenesis. Biochemistry 34, 237–243.PubMedCrossRefGoogle Scholar
  40. Weretilnyk, E.A. and Hanson, A.D. (1990) Molecular cloning of a plant betaine-aldehyde dehydrogenase, an enzyme implicated in the adaptation to salinity and drought. Proc Natl Acad Sci USA 87, 2745–2749.PubMedCrossRefGoogle Scholar
  41. Westlund, P., Fylling, A.C., Cederlund, E. and Jörnvall, H. (1994) 11-hydroxy-thromboxane B2 dehydrogenase is identical to cytosolic aldehyde dehydrogenase. FEBS Lett 345, 99–103.PubMedCrossRefGoogle Scholar
  42. Zinovieva, R.D., Tomarev, S.I. and Piatigorsky, J. (1993) Aldehyde dehydrogenase-derived omega-crystallins of squid and octopus. Specialization for lens expression. J Biol Chem 268, 11449–11455.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1999

Authors and Affiliations

  • John Perozich
    • 1
  • Hugh Nicholas
    • 2
  • Ronald Lindahl
    • 3
  • John Hempel
    • 4
  1. 1.Department of Molecular Genetics and BiochemistryUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Pittsburgh Supercomputing CenterCarnegie-Mellon UniversityPittsburghUSA
  3. 3.Department of Biochemistry and Molecular BiologyUniversity of South DakotaVermillionUSA
  4. 4.Department of Biological SciencesUniversity of PittsburghPittsburghUSA

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