N-methyl D-aspartate (NMDA) receptors play a key role in excitatory neurotransmission, learning, memory and synaptic plasticity. Their activity is modulated by the agonist glutamate and by the co-agonists D-Serine (D-Ser) and glycine (gly). In human brain, dimeric serine racemase (SRR), a pyridoxal 5'-phosphate-dependent enzyme (Smith et al. 2010), is a bifunctional enzyme mediating mainly the catabolism of L-Serine by alpha,beta-elimination of water to form pyruvate (Foltyn et al. 2005). A small part of L-Serine does not undergo deamination so SRR can also mediate the minor reversible isomerisation of L-Ser to D-Ser (De Miranda et al. 2000, Xia et al. 2004). Thus, D-Ser homeostasis in neurons is modulated by SRR, and therefore indirectly, modulates NMDA receptors. Targeting SRR could find potential in neurodegenerative diseases (Canu et al. 2014). Mg2+ and ATP stimulate SRR (De Miranda et al. 2002).
De Miranda, J,
serine racemase activity of PXLP-K56-SRR dimer [cytosol]