Reactome | PXLP-K56-SRR dimer deaminates L-Ser

PXLP-K56-SRR dimer deaminates L-Ser

Stable Identifier

R-HSA-9034539

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

ReviewStatus

5/5

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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 L-Serine catabolism by alpha,beta-elimination of water to form pyruvate (De Miranda et al. 2002, Foltyn et al. 2005). Part of L-Serine is not deaminated then SRR can also catalyse the isomerisation of L-Ser to D-Ser although this is very much a minor reaction. 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).

Literature References

PubMed ID	Title	Journal	Year
15536068	Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity Shleper, M, Toney, MD, Wolosker, H, Bendikov, I, Dumin, E, Li, P, De Miranda, J, Kartvelishvily, E, Panizzutti, R, Foltyn, VN	J. Biol. Chem.	2005
12393813	Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine Wolosker, H, De Miranda, J, Panizzutti, R, Foltyn, VN	Proc. Natl. Acad. Sci. U.S.A.	2002