Human serine racemase: moleular cloning, genomic organization and functional analysis.
High levels of D-serine are found in mammalian brain, where it is an endogenous agonist of the strichinine-insensitive site of N-methyl D-aspartate type of glutamate receptors. D-serine is enriched in protoplasmic astrocytes that occur in gray matter areas of the brain and was shown to be synthesized from L-serine. We now report cloning and expression of human serine racemase, 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 biosynthetic threonine dehydratase. Northern-blot analysis show high levels of human serine racemase in areas known to contain large amounts of endogenous D-serine, such as hippocampus and corpus callosum. Robust synthesis of D-serine was detected in cells transfected with human serine racemase, demonstrating the conservation of D-amino acid metabolism in humans. Serine racemase may be a therapeutic target in psychiatric diseases as supplementation of D-serine 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 boundaries of the human serine racemase gene will be useful to search for mutations in neuropsychiatric disorders.
De Miranda
J
J
Departamento de Bioquímica Médica, Instituto de Ciências Biomédicas, RJ 21491-590, Rio de Janeiro, Brazil.
Santoro
A
A
Engelender
S
S
Wolosker
H
H
D000595:Amino Acid Sequence; D001483:Base Sequence; D015152:Blotting, Northern; D001921:Brain / Q000201:enzymology; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000737:chemistry / Q000235:genetics; D005091:Exons; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019998:Racemases and Epimerases / Q000235:genetics* / Q000378:metabolism; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D017386:Sequence Homology, Amino Acid; D000099300:Serine Racemase
D018076:DNA, Complementary; D012333:RNA, Messenger; D019998:Racemases and Epimerases; D000099300:Serine Racemase