D-丝氨酸与丝氨酸消旋酶
D-Serine and Serine Racemase
DOI: 10.12677/HJBM.2013.32003, PDF, HTML, XML,  被引量    国家自然科学基金支持
作者: 冯延琼*, 石亚伟：山西大学生物技术研究所，教育部化学生物学与分子工程重点实验室，太原；肖虹：山西医科大学第一医院病理科，太原
关键词: 丝氨酸消旋酶；D-丝氨酸；结构；机理；功能；调控；Serine Racemase; D-Serine; Structure; Function; Mechanism; Regulation
摘要: D-丝氨酸主要存在于哺乳动物的前脑，海马区和纹状体，作为胶质细胞释放的神经递质，作用于NMDA (N-methyl-D-aspartate receptor)受体，引起中枢神经系统中信号的传导。在突触可塑性，学习和记忆等方面起重要作用。丝氨酸消旋酶是一种磷酸吡多醛依赖酶，在ATP和Mg2+的辅助下，通过消旋作用将L型丝氨酸转变为D型丝氨酸。对于神经及精神性疾病，丝氨酸消旋酶可能是一个新的治疗靶点。本文从D-丝氨酸和丝氨酸消旋酶的结构性质，作用机理，功能，调控等方面进行了阐述。
Abstract: D-serine mainly distributed in the mammalian forebrain, hippocampus and striatum, which as neurotransmit-ters from glial cells, target at NMDA receptors, and cause central nervous system signal transduction. A new neuro-transmitter of D-serine is found playing an important role in synaptic plasticity, learning and memory. Serine racemase (SR) is a pyridoxal 5'-phosphate(PLP)-dependent enzyme that catalyzes the interconversion of L- and D-serine. Serine racemase may be a new target for the neurological and psychiatric diseases. In this review, the recent advances in D-serine and serine racemase with the aspects of structure, function, mechanism and regulation will be discussed.
文章引用：冯延琼, 肖虹, 石亚伟. D-丝氨酸与丝氨酸消旋酶[J]. 生物医学, 2013, 3(2): 12-16. http://dx.doi.org/10.12677/HJBM.2013.32003

参考文献

[1] N. Fujii. D-amino acids in living higher organisms. Origins of Life and Evolution of Biospheres, 2002, 32(2): 103-127.
[2] M. J. Schell, M. E. Molliver and S. H. Snyder. D-serine, an endogenus synaptic modulator: Localization to astrocytes and glutamate-stimulated release. Proceedings of National Academy Science USA, 1995, 92(9): 3948-3952.
[3] M. J. Schell, R. O. Brady Jr, M. E. Molliver, et al. D-serine as a neuromodulator: Regional and development localization in rat brain glia resemble NMDA receptors. Neuroscience, 1997, 17(5): 1604-1615.
[4] H. Wolosker, R. Panizzutti and J. De Miranda. Neurobiology through the looking-glass:d-serine as a new glial-derived trans-mitter. Neurochemistry international, 2001, 41(5): 327-332.
[5] A. K. Mustafa, P. M. Kim and S. H. Snyder. D-serine as a puta-tive glial neurotransmitter. Neuron Glia Biology, 2004, 8(3): 275-281.
[6] C. S. Ribeiro, M. Reis, R. Panizzutti., et al. Glial transport of the neuromodulator d-serine. Brain Research, 2000, 929(2): 202- 209.
[7] R. Panizzutti, J. De Miranda, C. S. Ribeiro, et al. A new strateg to decrease N-methyl-D-aspartate (NMDA) receptor coactiva-tion:inhibition of D-serine synthesisi by converting serine race-mase into an eliminase. Proceedings of National Academy Sci-ence USA, 2001, 98(9): 5294-5299.
[8] J. De Miranda, A. Santoro, S. Enqelender, et al. Human serine racemase: Molecular cloning, genomic organization and func-tional analysis. Gene, 2000, 256(1-2): 183-188.
[9] H. Wolosker, K. N. Sheth, M. Takahashi, et al. Purification of serine racemase: Biosynthesis of the neuromodulator D-serine. Neurobiology, 1999, 96(2): 721-725.
[10] F. Baumgart, J. M. Manchen and I. Rodrıguez-Crespo. D-Amino acids in the brain: The biochemistry of brain serine racemase. FEBS Journal 2008, 275(14): 3538-3545.
[11] F. Baumgart, J. M. Manchen and I. Rodrıguez-Crespo. Insights into the activation of brain serine racemase by the multi-PDZ domain glutamate receptor interacting protein, divalent cations and ATP. FEBS Journal, 2007, 274(17): 4561-4571.
[12] M. Goto, T. Yamauchi, N. Kamiya, et al. Crystal structure of a homolog of mammalian serine racemase from Schizosaccharo-myces pombe. Biological Chemistry, 2009, 284(38): 25944-25952.
[13] M. A. Smith, V. Mack, A. Ebneth, et al. The structure of mam-malian serine racemase: Evidence for conformational changes upon inhibitor binding. Biological Chemistry, 2010, 285(17): 12873-12881.
[14] V. N. Foltyn, I. Bendikov, J. De Miranda, et al. Serine racemase modulates intracellular D-serine levels through an alpha, beta- elimination activity. Biological Chemistry, 2005, 280(3): 1754- 1763.
[15] M. D. Toney. Reaction specificity in pyridoxal phosphate en-zymes. Archives of Biochemistry and Biophysics, 2005, 433(1): 279-287.

为你推荐