Serine racemase: A glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)13409-13414
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume96
Issue number23
DOIs
StatePublished - Nov 9 1999

ASJC Scopus subject areas

  • General

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