Cloning and characterization of a putative human D-2-hydroxyacid dehydrogenase in chromosome 9q

There is little information on D-isomer-specific dehydrogenases in humans. Identification of D-2-hydroxy-glutaric aciduria, an inherited metabolic dis order associated with severe neurological dysfunction, highlights the role of D-isomers in human metabolism. The possibility of a defect in D-2-hydrox yglutarate dehydrogenation prompted us to employ E, coli D-2-hydroxyacid de hydrogenase 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 dehydrog enase (38%), and formate dehydrogenase (36%) at the amino acid level. The g ene is expressed ubiquitously in tissue, most abundantly in liver, and was mapped to chromosome 9q between markers WI-3028 and WI-93330, To our knowle dge this is the first cloning and characterization of the cDNA for a human D-isomer specific NAD(+)-dependent 2-hydroxyacid dehydrogenase. (C) 2000 Ac ademic Press.