The majority of synapses in the central nervous sy
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The majority of synapses in the central nervous system utilize glutamate as a neurotransmitter to produce rapid neuronal excitation. Glutamate has a diverse array of receptors that can be categorized into two groups: ionotropic and metabotropic. The ionotropic receptors are subdivided into two distinct types: 1) receptors for N-methyl D-aspartate (NMDAR) and 2) non-NMDA receptors for AMPA and kainate. NMDA receptors require coactivation at both glutamate and glycine sites. D-serine is a D-amino acid found in mammalian tissues that can act as a potent ligand for the glycine site on NMDA receptors. D-serine is made by the enzyme serine racemase, which is a member of the pyridoxal-5' phosphate (PLP)-dependent enzyme family. Serine racemase mRNA is expressed in brain and liver, and serine racemase protein is expressed in glial cells. Degradation of D-serine by D-amino acid oxidase attenuates NMDA receptor-mediated calcium influx, and implicates D-serine as an endogenouse modulator of NMDA receptor function. Thus, glial cell production of D-serine via serine racemase activity may be an important system for modulation of synaptic transmission.
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