D-amino acids as putative neurotransmitters: Focus on D-serine
D-amino acids as putative neurotransmitters: Focus on D-serine
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DOI：
10.1023/a:1007586314648
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发表时间：
2000-05-01
影响因子：
4.4
通讯作者：
Kim, PM
中科院分区：
文献类型：
--
作者：
Snyder, SH;Kim, PM
在哺乳动物体内的20种氨基酸中，只有丝氨酸和天冬氨酸以D-构型以及L-构型大量存在。D-丝氨酸选择性地集中在脑中，定位于包裹突触的原生质星形胶质细胞，并且分布类似于谷氨酸受体的N-甲基-D-天冬氨酸（NMDA）亚型。已发现D-丝氨酸作为NMDA受体的“甘氨酸”位点的内源性配体起作用。这方面的证据包括D-丝氨酸比甘氨酸更有效地激活该位点，并且降解D-丝氨酸以及其他中性D-氨基酸的D-氨基酸氧化酶显著减弱NMDA神经传递。D-丝氨酸也由丝氨酸消旋酶形成，丝氨酸消旋酶是最近克隆的将L-丝氨酸转化为D-丝氨酸的酶。因此，在许多方面，D-丝氨酸满足了将其功能定义为神经递质的标准，并挑战了与神经传递有关的教条，因为它是来自神经胶质而不是神经元的氨基酸的“非天然”异构形式。
Of the twenty amino acids in the mammalian body, only serine and aspartate occur in D-configuration as well as L-configuration in significant amount. D-serine is selectively concentrated in the brain, localized to protoplasmic astrocytes that ensheath synapses and distributed similarly to N-methyl-D-aspartate (NMDA) subtype of glutamate receptors. D-serine has been found to function as an endogenous ligand for the "glycine" site of the NMDA receptor. Evidences for this include the greater potency of D-serine to activate this site than glycine, and D-amino acid oxidase, which degrades D-serine as well as other neutral D-amino acids, markedly attenuates NMDA neurotransmission, D-serine is also formed by serine racemase, a recently cloned enzyme that converts L-serine to D-serine. Thus, in many ways D-serine fulfills criteria for defining its functionality as a neurotransmitter and challenges the dogma relating to neurotransmission, for it is the "unnatural" isomeric form of an amino acid derived from glia rather than neurons.