Metabolism of the neuromodulator D-serine

Cell Mol Life Sci. 2010 Jul;67(14):2387-404. doi: 10.1007/s00018-010-0307-9. Epub 2010 Mar 2.


Over the past years, accumulating evidence has indicated that D-serine is the endogenous ligand for the glycine-modulatory binding site on the NR1 subunit of N-methyl-D-aspartate receptors in various brain areas. D-Serine is synthesized in glial cells and neurons by the pyridoxal-5' phosphate-dependent enzyme serine racemase, and it is released upon activation of glutamate receptors. The cellular concentration of this novel messenger is regulated by both serine racemase isomerization and elimination reactions, as well as by its selective degradation catalyzed by the flavin adenine dinucleotide-containing flavoenzyme D-amino acid oxidase. Here, we present an overview of the current knowledge of the metabolism of D-serine in human brain at the molecular and cellular levels, with a specific emphasis on the brain localization and regulatory pathways of D-serine, serine racemase, and D-amino acid oxidase. Furthermore, we discuss how D-serine is involved with specific pathological conditions related to N-methyl-D-aspartate receptors over- or down-regulation.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Brain / metabolism*
  • D-Amino-Acid Oxidase / chemistry
  • D-Amino-Acid Oxidase / genetics
  • D-Amino-Acid Oxidase / metabolism
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Mental Disorders / metabolism
  • Neurodegenerative Diseases / metabolism
  • Neurotransmitter Agents / metabolism*
  • Racemases and Epimerases / chemistry
  • Racemases and Epimerases / genetics
  • Racemases and Epimerases / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Serine / metabolism*
  • Stereoisomerism


  • Neurotransmitter Agents
  • Receptors, N-Methyl-D-Aspartate
  • Serine
  • D-Amino-Acid Oxidase
  • Racemases and Epimerases
  • serine racemase