Human serine racemase: moleular cloning, genomic organization and functional analysis

High levels of D-serine are found in mammalian brain, where it is an endoge nous agonist of the strichinine-insensitive site of N-methyl D-aspartate ty pe of glutamate receptors. D-serine is enriched in protoplasmic astrocytes that occur in gray matter areas of the brain and was shown to be synthesize d from L-serine. We now report cloning and expression of human serine racem ase, an enzyme that catalyses the synthesis of D-serine from L-serine. The enzyme displays a high homology to the murine serine racemase. It contains a pyridoxal 5'-phosphate attachment sequence similar to bacterial biosynthe tic threonine dehydratase. Northern-blot analysis show high levels of human serine racemase in areas known to contain large amounts of endogenous D-se rine, such as hippocampus and corpus callosum. Robust synthesis of D-serine was detected in cells transfected with human serine racemase, demonstratin g the conservation of D-amino acid metabolism in humans. Serine racemase ma y be a therapeutic target in psychiatric diseases as supplementation of D-s erine greatly improves schizophrenia symptoms. We identify the human serine racemase genomic structure and show that the gene encompasses seven exons and localizes to chromosome 17q13.3. Identification of the intron-exon boun daries of the human serine racemase gene will be useful to search for mutat ions in neuropsychiatric disorders. (C) 2000 Elsevier Science B.V. All righ ts reserved.