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 though t not to occur in mammals. Recently, high levels of D-serine have been foun d in mammalian brain where it activates glutamate/N-methyl-D-aspartate rece ptors by interacting with the "glycine site" of the receptor. Because amino acid racemases are thought to be restricted to bacteria and insects, the o rigin of D-serine in mammals has been puzzling. We now report cloning and e xpression of serine racemase, an enzyme catalyzing the formation of D-serin e from L-serine, Serine racemase is a protein representing an additional fa mily of pyridoxal-5' phosphate-dependent enzymes in eukaryotes, The enzyme is enriched in rat brain where it occurs in glial cells that possess high l evels of D-serine in vivo, Occurrence of serine racemase in the brain demon strates the conservation of D-amino acid metabolism in mammals with implica tions for the regulation of N-methyl-D-aspartate neurotransmission through glia-neuronal interactions.