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

Synonyms

L-serine => NH4(+) + pyruvate

ReviewStatus

4/5

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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 (Glu) 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) is a bifunctional enzyme mediating mainly L-serine catabolism to form pyruvate (De Miranda et al. 2002, Foltyn et al. 2005). SRR can also catalyze the isomerisation of L-Ser to D-Ser, consistent with the hypothesis that SRR modulation of D-Ser homeostasis in neurons could indirectly modulate NMDA receptors. Targeting SRR could find potential in neurodegenerative diseases (Canu et al. 2014).

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
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