D-amino acids as putative neurotransmitters: Focus on D-serine

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184 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)553-560
Number of pages8
JournalNeurochemical Research
Issue number5
StatePublished - 2000


  • Astrocytes
  • Bergmann glia
  • D-aspartate
  • D-serine
  • N-methyl-D-aspartate (NMDA) receptor

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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