title: Cloning and characterization of a putative human d-2-hydroxyacid dehydrogenase in chromosome 9q.
abstract: There is little information on d-isomer-specific dehydrogenases in humans. Identification of d-2-hydroxyglutaric aciduria, an inherited metabolic disorder associated with severe neurological dysfunction, highlights the role of d-isomers in human metabolism. The possibility of a defect in d-2-hydroxyglutarate dehydrogenation prompted us to employ E. coli d-2-hydroxyacid dehydrogenase cDNA to search the human expressed sequence tags database. Two human EST homologues were retrieved and sequenced. Analysis showed the two clones were identical with 1258 nucleotides encoding 248 amino acids of the putative human d-2-hydroxyacid dehydrogenase. It was highly homologous to bacterial d-2-hydroxyacid dehydrogenases (46%), d-phosphoglycerate dehydrogenase (38%), and formate dehydrogenase (36%) at the amino acid level. The gene is expressed ubiquitously in tissue, most abundantly in liver, and was mapped to chromosome 9q between markers WI-3028 and WI-93330. To our knowledge this is the first cloning and characterization of the cDNA for a human d-isomer specific NAD(+)-dependent 2-hydroxyacid dehydrogenase.
authors.affiliation: Division of Genetics and Metabolism, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: T
authors.initials: T
authors.lastname: Huang
authors.forename: W
authors.initials: W
authors.lastname: Yang
authors.forename: A C
authors.initials: AC
authors.lastname: Pereira
authors.forename: W J
authors.initials: WJ
authors.lastname: Craigen
authors.forename: V E
authors.initials: VE
authors.lastname: Shih
mesh_terms: D000429:Alcohol Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D000595:Amino Acid Sequence; D001483:Base Sequence; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D006801:Humans; D007770:L-Lactate Dehydrogenase; D045022:Lactate Dehydrogenases; D008969:Molecular Sequence Data; D017386:Sequence Homology, Amino Acid
chemical_list: D000429:Alcohol Oxidoreductases; D045022:Lactate Dehydrogenases; D007770:L-Lactate Dehydrogenase; C071195:D-lactate dehydrogenase; C021379:D-2-hydroxyacid dehydrogenase