Editing Serine (section)

=== Signaling ===
<small>D</small>-Serine, synthesized in neurons by [[serine racemase]] from <small>L</small>-serine (its [[enantiomer]]), serves as a neuromodulator by coactivating [[NMDA receptor]]s, making them able to open if they then also bind [[glutamate]]. <small>D</small>-serine is a potent [[agonist]] at the [[glycine]] site (NR1) of canonical diheteromeric [[NMDA receptor]]s. For the receptor to open, glutamate and either glycine or <small>D</small>-serine must bind to it; in addition a pore blocker must not be bound (e.g. Mg<sup>2+</sup> or Zn<sup>2+</sup>).<ref>{{cite journal |vauthors=Liu Y, Hill RH, Arhem P, von Euler G |title=NMDA and glycine regulate the affinity of the Mg2+-block site in NR1-1a/NR2A NMDA receptor channels expressed in Xenopus oocytes |journal=Life Sciences |volume=68 |issue=16 |pages=1817–1826 |year=2001 |pmid=11292060 |doi=10.1016/S0024-3205(01)00975-4 }}</ref> Some research has shown that <small>D</small>-serine is a more potent agonist at the NMDAR glycine site than glycine itself.<ref name="MacKay 2019">{{cite journal | last1=MacKay | first1=Mary-Anne B. | last2=Kravtsenyuk | first2=Maryana | last3=Thomas | first3=Rejish | last4=Mitchell | first4=Nicholas D. | last5=Dursun | first5=Serdar M. | last6=Baker | first6=Glen B. | title=D-Serine: Potential Therapeutic Agent and/or Biomarker in Schizophrenia and Depression? | journal=Frontiers in Psychiatry | date=6 February 2019 | volume=10 | page=25 | issn=1664-0640 | doi=10.3389/fpsyt.2019.00025 | pmid=30787885 | pmc=6372501 | quote=D-Serine is more potent than glycine as a coagonist at the NMDA receptor, has a regional distribution in the brain that is similar to that of NMDA receptors and appears to be more closely associated with synaptic NMDA receptors than glycine (which is more closely associated with non-synaptic NMDA receptors).| doi-access=free }}</ref><ref name="Wolosker 2020">{{cite journal | last1=Wolosker | first1=Herman | last2=Balu | first2=Darrick T. | title=D-Serine as the gatekeeper of NMDA receptor activity: implications for the pharmacologic management of anxiety disorders | journal=Translational Psychiatry | volume=10 | issue=1 | date=9 June 2020 | page=184 | issn=2158-3188 | doi=10.1038/s41398-020-00870-x | pmid=32518273 | pmc=7283225 | quote=D-Serine is functionally a more potent activator of synaptic NMDARs than glycine, and mounting evidence suggests that it serves as the major NMDAR co-agonist in limbic brain regions implicated in neuropsychiatric disorders.}}</ref> However, D-serine has been shown to work as an antagonist/inverse co-agonist of [[NMDA receptor|''t''-NMDA receptors]] through the glycine binding site on the GluN3 subunit.<ref>{{cite journal |last1=Pilli |first1=J. |last2=Kumar |first2=S. S. |date=2012-10-11 |title=Triheteromeric N-methyl-D-aspartate receptors differentiate synaptic inputs onto pyramidal neurons in somatosensory cortex: involvement of the GluN3A subunit |url=https://pubmed.ncbi.nlm.nih.gov/22814002 |journal=Neuroscience |volume=222 |pages=75–88 |doi=10.1016/j.neuroscience.2012.07.020 |issn=1873-7544 |pmid=22814002|s2cid=23158971 }}</ref><ref>{{cite journal |last1=Beesley |first1=Stephen |last2=Kumar |first2=Sanjay S. |date=2023-11-01 |title=The t-N-methyl-d-aspartate receptor: Making the case for d-Serine to be considered its inverse co-agonist |journal=Neuropharmacology |volume=238 |pages=109654 |doi=10.1016/j.neuropharm.2023.109654 |issn=1873-7064 |pmid=37437688|doi-access=free }}</ref>