A new strategy to decrease N-methyl-d-aspartate (NMDA) receptor coactivation: Inhibition of d-serine synthesis by converting serine racemase into an eliminase Export

@article{citeulike:3660166, abstract = {10.1073/pnas.091002298 Serine racemase is a brain-enriched enzyme that synthesizes -serine, an endogenous modulator of the glycine site of -methyl--aspartate (NMDA) receptors. We now report that serine racemase catalyzes an elimination reaction toward a nonphysiological substrate that provides a powerful tool to study its neurobiological role and will be useful to develop selective enzyme inhibitors. Serine racemase catalyzes robust elimination of -serine -sulfate that is 500 times faster than the physiological racemization reaction, generating sulfate, ammonia, and pyruvate. This reaction provides the most simple and sensitive assay to detect the enzyme activity so far. We establish stable cell lines expressing serine racemase and show that serine racemase can also be converted into a powerful eliminase in cultured cells, while the racemization of -serine is inhibited. Likewise, -serine -sulfate inhibits the synthesis of -serine in primary astrocyte cultures. We conclude that the synthetic compound -serine -sulfate is a better substrate than -serine as well as an inhibitor of -serine synthesis. Inhibition of serine racemase provides a new strategy to selectively decrease NMDA receptor coactivation and may be useful in conditions in which overstimulation of NMDA receptors plays a pathological role.}, author = {Panizzutti, Rog\'{e}rio and De Miranda, Joari and Ribeiro, C\'{a}tia S. and Engelender, Simone and Wolosker, Herman}, citeulike-article-id = {3660166}, citeulike-linkout-0 = {http://dx.doi.org/10.1073/pnas.091002298}, citeulike-linkout-1 = {http://www.pnas.org/content/98/9/5294.abstract}, citeulike-linkout-2 = {http://www.pnas.org/content/98/9/5294.full.pdf}, citeulike-linkout-3 = {http://view.ncbi.nlm.nih.gov/pubmed/11309496}, citeulike-linkout-4 = {http://www.hubmed.org/display.cgi?uids=11309496}, day = {24}, doi = {10.1073/pnas.091002298}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, keywords = {nmda, serinracemase}, month = {April}, number = {9}, pages = {5294--5299}, posted-at = {2008-11-22 11:25:39}, priority = {5}, title = {A new strategy to decrease N-methyl-d-aspartate (NMDA) receptor coactivation: Inhibition of d-serine synthesis by converting serine racemase into an eliminase}, url = {http://dx.doi.org/10.1073/pnas.091002298}, volume = {98}, year = {2001} }

TY - JOUR ID - citeulike:3660166 L3 - citeulike-article-id:3660166 N2 - 10.1073/pnas.091002298 Serine racemase is a brain-enriched enzyme that synthesizes -serine, an endogenous modulator of the glycine site of -methyl--aspartate (NMDA) receptors. We now report that serine racemase catalyzes an elimination reaction toward a nonphysiological substrate that provides a powerful tool to study its neurobiological role and will be useful to develop selective enzyme inhibitors. Serine racemase catalyzes robust elimination of -serine -sulfate that is 500 times faster than the physiological racemization reaction, generating sulfate, ammonia, and pyruvate. This reaction provides the most simple and sensitive assay to detect the enzyme activity so far. We establish stable cell lines expressing serine racemase and show that serine racemase can also be converted into a powerful eliminase in cultured cells, while the racemization of -serine is inhibited. Likewise, -serine -sulfate inhibits the synthesis of -serine in primary astrocyte cultures. We conclude that the synthetic compound -serine -sulfate is a better substrate than -serine as well as an inhibitor of -serine synthesis. Inhibition of serine racemase provides a new strategy to selectively decrease NMDA receptor coactivation and may be useful in conditions in which overstimulation of NMDA receptors plays a pathological role. IS - 9 JF - Proceedings of the National Academy of Sciences of the United States of America EP - 5299 TI - A new strategy to decrease N-methyl-d-aspartate (NMDA) receptor coactivation: Inhibition of d-serine synthesis by converting serine racemase into an eliminase VL - 98 SP - 5294 KW - nmda KW - serinracemase AU - Panizzutti, Rogério AU - De Miranda, Joari AU - Ribeiro, Cátia AU - Engelender, Simone AU - Wolosker, Herman PY - 2001/04/24/ UR - http://dx.doi.org/10.1073/pnas.091002298 ER -