Comparative and evolutionary studies of ALDH18A1 genes and proteins. (1st October 2017)

• Record Type: Journal Article
• Authors: Holmes, Roger S.
• Is Part Of: Chemico-biological interactions. Volume 276(2017)
• Page Start: 2
• Page End: 8
• Publication Date: 2017-10-01
• Subjects: Aldehyde dehydrogenases -- Bifunctional enzyme -- ALDH18A1 -- Glutamyl kinase -- GK -- Glutamyl phosphate reductase -- GPR -- Vertebrates -- Invertebrates -- Evolution -- Phylogeny -- Primordial gene -- Gene integration -- Transcription factor binding sites -- CpG islands; ALDH aldehyde dehydrogenase -- P5CS delta 1-pyrroline-5-carboxylate synthase -- GK gamma-glutamyl kinase -- GPR gamma-glutamyl phosphate reductase -- GSA glutamyl-5-semialdehyde -- EC Enzyme Commission -- BLAST Basic Local Alignment Search Tool -- BLAT Blast-Like Alignment Tool -- NCBI National Center for Biotechnology Information -- AceView NCBI Based representation of public mRNAs -- TFBS transcription factor binding sites -- UTR Untranslated Gene Region -- CpG region of high density of guanine-cytosine dinucleotides -- mRNA messenger RNA; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2016.12.012
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Vertebrate ALDH18A 1 genes encode a bifunctional mitochondrial enzyme, catalyzing a 2-step conversion of glutamate to glutamyl semialdehyde, subsequently converted into proline, ornithine and arginine. Bioinformatic analyses of vertebrate and invertebrate genomes were undertaken using known ALDH18A1 amino acid sequences. G5K (glutamyl kinase) and GPR (glutamyl phosphate reductase) domain sequences were identified for all vertebrate and invertebrate genomes examined, whereas bacterial sequences encoded separate enzymes. Vertebrate ALDH18A1 (also called P5CS) sequences were highly conserved throughout vertebrate evolution. A mechanism for generating two major vertebrate ALDH18A1 isoforms is proposed with 'a' isoform containing Asn239-Val240 with wide tissue expression, whereas the 'b' isoform lacking the dipeptide has been reported in gut tissues. Phylogenetic analyses describe the relationships and potential origins of the ALDH18A1 gene during vertebrate and invertebrate evolution and a proposal for generating the bifunctional vertebrate and invertebrate ALDH18A1 gene from a bacterial operon ( proBA ) encoding G5K and GPR. A more recent Aldh18a1 gene duplication event has apparently occurred with a primordial rat genome. Highlights: ALDH18A1 has two domains: glutamate 5-kinase and gamma-glutamyl phosphate reductase. Two major isoforms were observed for all vertebrate ALDH18A1 genes. Two amino acid insert (239Asn-240Val) observed in 'a' isoform. Amino acid sequences highly conserved during vertebrate evolution. A gene fusion model is presented for appearance of multiple domain ALDH18A1 gene.