title: Phylogeny and evolution of aldehyde dehydrogenase-homologous folate enzymes.
abstract: Folate coenzymes function as one-carbon group carriers in intracellular metabolic pathways. Folate-dependent reactions are compartmentalized within the cell and are catalyzed by two distinct groups of enzymes, cytosolic and mitochondrial. Some folate enzymes are present in both compartments and are likely the products of gene duplications. A well-characterized cytosolic folate enzyme, FDH (10-formyltetrahydro-folate dehydrogenase, ALDH1L1), contains a domain with significant sequence similarity to aldehyde dehydrogenases. This domain enables FDH to catalyze the NADP(+)-dependent conversion of short-chain aldehydes to corresponding acids in vitro. The aldehyde dehydrogenase-like reaction is the final step in the overall FDH mechanism, by which a tetrahydrofolate-bound formyl group is oxidized to CO(2) in an NADP(+)-dependent fashion. We have recently cloned and characterized another folate enzyme containing an ALDH domain, a mitochondrial FDH. Here the biological roles of the two enzymes, a comparison of the respective genes, and some potential evolutionary implications are discussed. The phylogenic analysis suggests that the vertebrate ALDH1L2 gene arose from a duplication event of the ALDH1L1 gene prior to the emergence of osseous fish >500 millions years ago.
authors.affiliation: Department of Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA.
authors.forename: Kyle C
authors.initials: KC
authors.lastname: Strickland
authors.forename: Roger S
authors.initials: RS
authors.lastname: Holmes
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Oleinik
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Krupenko
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Krupenko
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D019143:Evolution, Molecular; D005091:Exons / Q000235:genetics; D005492:Folic Acid / Q000378:metabolism*; D023281:Genomics; D006801:Humans; D007448:Invertebrates / Q000201:enzymology / Q000235:genetics; D000587:Oxidoreductases Acting on CH-NH Group Donors; D010802:Phylogeny; D017386:Sequence Homology, Amino Acid; D000099295:Formyltetrahydrofolate Dehydrogenase
chemical_list: D000444:Aldehyde Dehydrogenase; D005492:Folic Acid; D000587:Oxidoreductases Acting on CH-NH Group Donors; D000099295:Formyltetrahydrofolate Dehydrogenase