D-amino acids as putative neurotransmitters: focus on D-serine.
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.
Snyder
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The Johns Hopkins University, School of Medicine Department of Neuroscience, Baltimore, MD 21205, USA.
Kim
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PM
D000596:Amino Acids / Q000737:chemistry / Q000502:physiology*; D000818:Animals; D001253:Astrocytes / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D006801:Humans; D008322:Mammals; D018377:Neurotransmitter Agents / Q000737:chemistry / Q000502:physiology*; D012694:Serine / Q000737:chemistry / Q000502:physiology*; D013237:Stereoisomerism
D000596:Amino Acids; D018377:Neurotransmitter Agents; D012694:Serine