Serine racemase:: A glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission
Serine racemase:: A glial enzyme synthesizing D-serine to regulate glutamate-N-methyl-D-aspartate neurotransmission
复制标题
DOI：
10.1073/pnas.96.23.13409
复制
发表时间：
1999-11-09
影响因子：
11.1
通讯作者：
Snyder, SH
中科院分区：
文献类型：
--
作者：
Wolosker, H;Blackshaw, S;Snyder, SH
虽然D氨基酸在细菌中很突出，但它们通常被认为不存在于哺乳动物中。最近，在哺乳动物脑中发现了高水平的D-丝氨酸，其通过与受体的“甘氨酸位点”相互作用来激活谷氨酸/N-甲基-D-天冬氨酸受体。由于氨基酸消旋酶被认为仅限于细菌和昆虫，因此哺乳动物中D-丝氨酸的起源一直令人困惑。我们现在报道丝氨酸消旋酶的克隆和表达，丝氨酸消旋酶是催化从L-丝氨酸形成D-丝氨酸的酶，丝氨酸消旋酶是真核生物中代表吡哆醛-5 '磷酸依赖酶的另一个家族的蛋白质，该酶在大鼠脑中富集，在那里它存在于体内具有高水平D-丝氨酸的神经胶质细胞中，丝氨酸消旋酶在脑中的发生证明了哺乳动物中D-氨基酸代谢的保守性，并暗示通过胶质细胞-神经元相互作用调节N-甲基-D-天冬氨酸神经传递。
Although D amino acids are prominent in bacteria, they generally are thought not to occur in mammals. Recently, high levels of D-serine have been found in mammalian brain where it activates glutamate/N-methyl-D-aspartate receptors by interacting with the "glycine site" of the receptor. Because amino acid racemases are thought to be restricted to bacteria and insects, the origin of D-serine in mammals has been puzzling. We now report cloning and expression of serine racemase, an enzyme catalyzing the formation of D-serine from L-serine, Serine racemase is a protein representing an additional family of pyridoxal-5' phosphate-dependent enzymes in eukaryotes, The enzyme is enriched in rat brain where it occurs in glial cells that possess high levels of D-serine in vivo, Occurrence of serine racemase in the brain demonstrates the conservation of D-amino acid metabolism in mammals with implications for the regulation of N-methyl-D-aspartate neurotransmission through glia-neuronal interactions.