Purification of serine racemase: Biosynthesis of the neuromodulator D-serine
Purification of serine racemase: Biosynthesis of the neuromodulator D-serine
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DOI：
10.1073/pnas.96.2.721
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发表时间：
1999-01-19
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;Sheth, KN;Snyder, SH
高水平的D-丝氨酸存在于哺乳动物脑中，在那里它似乎是N-甲基-D-天冬氨酸受体的甘氨酸位点的内源性配体。在大鼠大脑皮层的神经胶质培养物中，D-丝氨酸在II型星形胶质细胞中富集，并且在用非N-甲基-D-天冬氨酸谷氨酸受体的激动剂刺激时释放，大鼠脑内高水平的D-丝氨酸意味着生物合成途径的存在。我们从大鼠脑中纯化了一种可溶性酶，该酶催化L-丝氨酸直接外消旋为D-丝氨酸，纯化的丝氨酸消旋酶具有37 kDa的分子量，并且其活性需要吡哆醛5 '-磷酸。该酶对L-丝氨酸具有高度选择性，不能外消旋任何其他测试的氨基酸。性质，如pH值的最佳值，K-m值，磷酸吡哆醛的要求类似的细菌消旋酶，这表明生物合成途径的D-氨基酸是保守的从细菌到哺乳动物的大脑。
High levels of D-serine occur in mammalian brain, where it appears to be an endogenous ligand of the glycine site of N-methyl-D-aspartate receptors, In glial cul tures of rat cerebral cortex, D-serine is enriched in type II astrocytes and is released upon stimulation with agonists of non-N-methyl-D-aspartate glutamate receptors, The high levels of D-serine in discrete areas of rat brain imply the existence of a biosynthetic pathway, We have purified from rat brain a soluble enzyme that catalyzes the direct racemization of L-serine to D-serine, Purified serine racemase has a molecular mass of 37 kDa and requires pyridoxal 5'-phosphate for its activity. The enzyme is highly selective toward L-serine, failing to racemize any other amino acid tested. Properties such as pH optimum, K-m values, and the requirement for pyridoxal phosphate resemble those of bacterial racemases, suggesting that the biosynthetic pathway for D-amino acids is conserved from bacteria to mammalian brain.