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Neurochemical Research

, Volume 25, Issue 5, pp 553–560 | Cite as

D-Amino Acids as Putative Neurotransmitters: Focus on D-Serine

  • Solomon H. Snyder
  • Paul M. Kim
Article

Abstract

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.

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

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Copyright information

© Plenum Publishing Corporation 2000

Authors and Affiliations

  • Solomon H. Snyder
    • 1
  • Paul M. Kim
    • 1
  1. 1.School of Medicine Departments of Neuroscience, Pharmacology and Molecular Sciences and PsychiatryThe Johns Hopkins UniversityBaltimore

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