title: Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes.
abstract: Proline metabolism in mammals involves two other amino acids, glutamate and ornithine, and five enzymatic activities, Delta(1)-pyrroline-5-carboxylate (P5C) reductase (P5CR), proline oxidase, P5C dehydrogenase, P5C synthase and ornithine-delta-aminotransferase (OAT). With the exception of OAT, which catalyzes a reversible reaction, the other four enzymes are unidirectional, suggesting that proline metabolism is purpose-driven, tightly regulated, and compartmentalized. In addition, this tri-amino-acid system also links with three other pivotal metabolic systems, namely the TCA cycle, urea cycle, and pentose phosphate pathway. Abnormalities in proline metabolism are relevant in several diseases: six monogenic inborn errors involving metabolism and/or transport of proline and its immediate metabolites have been described. Recent advances in the Human Genome Project, in silico database mining techniques, and research in dissecting the molecular basis of proline metabolism prompted us to utilize functional genomic approaches to analyze human genes which encode proline metabolic enzymes in the context of gene structure, regulation of gene expression, mRNA variants, protein isoforms, and single nucleotide polymorphisms.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of New Mexico School of Medicine, Albuquerque, NM 87131, USA. ahu@salud.unm.edu
authors.forename: Chien-An A
authors.initials: CA
authors.lastname: Hu
authors.forename: D
authors.initials: D
authors.lastname: Bart Williams
authors.forename: Siqin
authors.initials: S
authors.lastname: Zhaorigetu
authors.forename: Shadi
authors.initials: S
authors.lastname: Khalil
authors.forename: Guanghua
authors.initials: G
authors.lastname: Wan
authors.forename: David
authors.initials: D
authors.lastname: Valle
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D015971:Gene Expression Regulation, Enzymologic; D015894:Genome, Human; D023281:Genomics; D006801:Humans; D008954:Models, Biological; D009953:Ornithine-Oxo-Acid Transaminase / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011392:Proline / Q000378:metabolism*; D011394:Proline Oxidase / Q000235:genetics / Q000378:metabolism; D020218:Response Elements; D013997:Time Factors; D014018:Tissue Distribution; D014508:Urea / Q000378:metabolism
chemical_list: D014508:Urea; D011392:Proline; D011394:Proline Oxidase; D009953:Ornithine-Oxo-Acid Transaminase