Of the twenty amino acids in the mammalian body, only serine and aspartate occur in D-configuration as well as L-configuration in significant amount. D-serine is selectively concentrated in the brain, localized to protoplasmic astrocytes that ensheath synapses and distributed similarly to N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. D-serine has been found to function as an endogenous ligand for the “glycine” site of the NMDA receptor. Evidences for this include the greater potency of D-serine to activate this site than glycine, and D-amino acid oxidase, which degrades D-serine as well as other neutral D-amino acids, markedly attenuates NMDA neurotransmission. D-serine is also formed by serine racemase, a recently cloned enzyme that converts L-serine to D-serine. Thus, in many ways D-serine fulfills criteria for defining its functionality as a neurotransmitter and challenges the dogma relating to neurotransmission, for it is the “unnatural” isomeric form of an amino acid derived from glia rather than neurons.
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Snyder, S.H., Kim, P.M. D-Amino Acids as Putative Neurotransmitters: Focus on D-Serine. Neurochem Res 25, 553–560 (2000). https://doi.org/10.1023/A:1007586314648
- N-methyl-D-aspartate (NMDA) receptor
- Bergmann glia