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 deamination and isomerisation of L-Serine. It can also catabolise D-Serine by alpha,beta-elimination of water to form pyruvate but at a rate 10-fold lower than for L-Serine (De Miranda et al. 2000, 2002, Foltyn et al. 2005). 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).
Shleper, M, Toney, MD, Wolosker, H, Bendikov, I, Dumin, E, Li, P, De Miranda, J, Kartvelishvily, E, Panizzutti, R, Foltyn, VN
Wolosker, H, De Miranda, J, Panizzutti, R, Foltyn, VN
D-serine ammonia-lyase activity of PXLP-K56-SRR dimer [cytosol]
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