Meta-Biol

• Pathways

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).