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- W2020952616 abstract "d-Serine is a brain-enriched d-amino acid that works as a transmitter-like molecule by physiologically activating NMDA receptors. Synthesis of d-serine is carried out by serine racemase (SR), a pyridoxal 5'-phosphate-dependent enzyme. In addition to carry out racemization, SR α,β-eliminates water from l- or d-serine, generating pyruvate and NH(4)(+). Here I review the main mechanisms regulating SR activity and d-serine dynamics in the brain. I propose a role for SR in a novel form of astrocyte-neuron communication-the serine shuttle, whereby astrocytes synthesize and export l-serine required for the synthesis of d-serine by the predominantly neuronal SR. d-Serine synthesized and released by neurons can be further taken up by astrocytes for storage and activity-dependent release. I discuss how SR α,β-elimination with d-serine itself may limit the achievable intracellular d-serine concentration, providing a mechanistic rationale on why neurons do not store as much d-serine as astrocytes. The higher content of d-serine in astrocytes appears to be related to increased d-serine stability, for their low SR expression will prevent substantial d-serine metabolism via α,β-elimination. SR and the serine shuttle pathway are therapeutic targets in neurodegenerative diseases in which NMDA receptor dysfunction plays pathological roles. This article is part of a Special Issue entitled: Pyridoxal Phospate Enzymology." @default.
- W2020952616 created "2016-06-24" @default.
- W2020952616 creator A5005170631 @default.
- W2020952616 date "2011-11-01" @default.
- W2020952616 modified "2023-10-14" @default.
- W2020952616 title "Serine racemase and the serine shuttle between neurons and astrocytes" @default.
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- W2020952616 doi "https://doi.org/10.1016/j.bbapap.2011.01.001" @default.
- W2020952616 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21224019" @default.
- W2020952616 hasPublicationYear "2011" @default.
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