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


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.

SUBMITTER: Wolosker H 

PROVIDER: S-EPMC23961 | biostudies-literature | 1999 Nov

REPOSITORIES: biostudies-literature

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

Wolosker H H   Blackshaw S S   Snyder S H SH  

Proceedings of the National Academy of Sciences of the United States of America 19991101 23


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  ...[more]

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