Reactome | PXLP-K56-SRR dimer isomerises L-Ser to D-Ser

PXLP-K56-SRR dimer isomerises L-Ser to D-Ser

Stable Identifier

R-HSA-9014766

Type

Reaction [transition]

Species

Homo sapiens

Compartment

cytosol

Synonyms

L-serine => D-serine

ReviewStatus

5/5

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PXLP-K56-SRR dimer isomerises L-Ser to D-Ser

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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). Dimeric serine racemase (SRR), a pyridoxal 5'-phosphate-dependent enzyme expressed in human brain (Smith et al. 2010) mediates the efficient conversion of L-Serine to pyruvate (Foltyn et al. 2005), but also mediates the slower 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, indirectly modulating NMDA receptor function. 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 Ciotti, MT, Pollegioni, L, Canu, N	Front Synaptic Neurosci	2014
20106978	The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding Smith, MA, Cesura, A, Barker, J, Mather, O, Ebneth, A, Mack, V, Wood, M, Moraes, I, Felicetti, B, Schonfeld, D	J. Biol. Chem.	2010
15193426	Characterization and localization of a human serine racemase Lu, P, Wei, N, Liu, Y, Chiu, CS, Lawlor, AM, Sur, C, Figueroa, DJ, Xia, M, Connolly, TM, Koblan, KS	Brain Res. Mol. Brain Res.	2004
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
11054547	Human serine racemase: moleular cloning, genomic organization and functional analysis Engelender, S, De Miranda, J, Wolosker, H, Santoro, A	Gene	2000
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