Serine racemase: a glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission.
Although D amino acids are prominent in bacteria, they generally are thought not to occur in mammals. Recently, high levels of D-serine have been found in mammalian brain where it activates glutamate/N-methyl-D-aspartate receptors by interacting with the "glycine site" of the receptor. Because amino acid racemases are thought to be restricted to bacteria and insects, the origin of D-serine in mammals has been puzzling. We now report cloning and expression of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine. Serine racemase is a protein representing an additional family of pyridoxal-5' phosphate-dependent enzymes in eukaryotes. The enzyme is enriched in rat brain where it occurs in glial cells that possess high levels of D-serine in vivo. Occurrence of serine racemase in the brain demonstrates the conservation of D-amino acid metabolism in mammals with implications for the regulation of N-methyl-D-aspartate neurotransmission through glia-neuronal interactions.
Wolosker
H
H
Departments of Neuroscience, The Johns Hopkins University, School of Medicine, 725 North Wolfe Street, Baltimore, MD 21205, USA.
Blackshaw
S
S
Snyder
S H
SH
D000595:Amino Acid Sequence; D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D001483:Base Sequence; D002460:Cell Line; D017931:DNA Primers; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D016202:N-Methylaspartate / Q000378:metabolism*; D019998:Racemases and Epimerases / Q000378:metabolism*; D051381:Rats; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000096:biosynthesis*; D000099300:Serine Racemase
D017931:DNA Primers; D016202:N-Methylaspartate; D019998:Racemases and Epimerases; D012694:Serine; D000099300:Serine Racemase