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

PXLP-K56-SRR dimer deaminates D-Ser

Stable Identifier

R-HSA-9014741

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

D-serine => NH4(+) + pyruvate

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 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).

Literature References

PubMed ID	Title	Journal	Year
24795622	Serine racemase: a key player in apoptosis and necrosis Canu, N, Ciotti, MT, Pollegioni, L	Front Synaptic Neurosci	2014
20106978	The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding Smith, MA, Mack, V, Ebneth, A, Moraes, I, Felicetti, B, Wood, M, Schonfeld, D, Mather, O, Cesura, A, Barker, J	J. Biol. Chem.	2010
15536068	Serine racemase modulates intracellular D-serine levels through an alpha,beta-elimination activity Foltyn, VN, Bendikov, I, De Miranda, J, Panizzutti, R, Dumin, E, Shleper, M, Li, P, Toney, MD, Kartvelishvily, E, Wolosker, H	J. Biol. Chem.	2005
11054547	Human serine racemase: moleular cloning, genomic organization and functional analysis De Miranda, J, Santoro, A, Engelender, S, Wolosker, H	Gene	2000
12393813	Cofactors of serine racemase that physiologically stimulate the synthesis of the N-methyl-D-aspartate (NMDA) receptor coagonist D-serine De Miranda, J, Panizzutti, R, Foltyn, VN, Wolosker, H	Proc. Natl. Acad. Sci. U.S.A.	2002