title: Serine racemase and the serine shuttle between neurons and astrocytes.
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.
authors.affiliation: Department of Biochemistry, B. Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa 31096, Israel. hwolosker@tx.technion.ac.il
authors.forename: Herman
authors.initials: H
authors.lastname: Wolosker
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000378:metabolism*; D055162:Biocatalysis; D006801:Humans; D008958:Models, Molecular; D009474:Neurons / Q000201:enzymology / Q000378:metabolism*; D011487:Protein Conformation; D019998:Racemases and Epimerases / Q000737:chemistry / Q000378:metabolism*; D000099300:Serine Racemase
chemical_list: D019998:Racemases and Epimerases; D000099300:Serine Racemase