title: Aldehyde dehydrogenase homologous folate enzymes: Evolutionary switch between cytoplasmic and mitochondrial localization.
abstract: Cytosolic and mitochondrial 10-formyltetrahydrofolate dehydrogenases are products of separate genes in vertebrates but only one such gene is present in invertebrates. There is a significant degree of sequence similarity between the two enzymes due to an apparent origin of the gene for the mitochondrial enzyme (ALDH1L2) from the duplication of the gene for the cytosolic enzyme (ALDH1L1). The primordial ALDH1L gene originated from a natural fusion of three unrelated genes, one of which was an aldehyde dehydrogenase. Such structural organization defined the catalytic mechanism of these enzymes, which is similar to that of aldehyde dehydrogenases. Here we report the analysis of ALDH1L1 and ALDH1L2 genes from different species and their phylogeny and evolution. We also performed sequence and structure comparison of ALDH1L enzymes possessing aldehyde dehydrogenase catalysis to those lacking this feature in an attempt to explain mechanistic differences between cytoplasmic ALDH1L1 and mitochondrial ALDH1L2 enzymes and to better understand their functional roles.
authors.affiliation: Department of Nutrition, UNC-Chapel Hill, UNC Nutrition Research Institute, Kannapolis, NC 28081, United States.
authors.forename: Natalia I
authors.initials: NI
authors.lastname: Krupenko
authors.affiliation: The Eskitis Institute for Drug Discovery and School of Natural Sciences, Griffith University, Nathan, 4111 Brisbane, Queensland, Australia.
authors.forename: Roger S
authors.initials: RS
authors.lastname: Holmes
authors.affiliation: Department of Pharmacology, Case Western Reserve University, Cleveland, OH 44106, United States.
authors.forename: Yaroslav
authors.initials: Y
authors.lastname: Tsybovsky
authors.affiliation: Department of Nutrition, UNC-Chapel Hill, UNC Nutrition Research Institute, Kannapolis, NC 28081, United States. Electronic address: sergey_krupenko@unc.edu.
authors.forename: Sergey A
authors.initials: SA
authors.lastname: Krupenko
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003593:Cytoplasm / Q000201:enzymology* / Q000378:metabolism*; D019143:Evolution, Molecular; D005492:Folic Acid / Q000378:metabolism*; D006801:Humans; D007448:Invertebrates / Q000201:enzymology / Q000378:metabolism; D008928:Mitochondria / Q000201:enzymology* / Q000378:metabolism*; D010802:Phylogeny; D014714:Vertebrates / Q000196:embryology / Q000378:metabolism; D015027:Zebrafish / Q000378:metabolism
chemical_list: D005492:Folic Acid; D000444:Aldehyde Dehydrogenase
keywords: ALDH1L enzymes; Aldehyde dehydrogenases; Enzyme mechanism; Evolution; Folate metabolism; Mitochondria