BIOSYNTHESIS OF CATECHOLAMINES

儿茶酚胺的生物合成

• 批准号: 3880872
• 负责人: S KAUFMAN
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF MENTAL HEALTH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3880872
• 关键词: adrenal medulla; catecholamines; corpus striatum; enzyme mechanism; enzyme structure; laboratory rat; neoplastic cell culture for noncancer research; neurochemistry; neurotransmitter biosynthesis; pheochromocytoma; phosphorylation; protein kinase A; pteridines; synaptosomes; tyrosine 3 monooxygenase

Previous studies in our laboratory have shown that tetrahydrobiopterin (BH4) activates a sine hydroxylase phosphatase in vitro. The present results,are consistent with these earlier findings and suggest that BH4 has a similar effect in intact rat striatal synaptosomes. An increase in intrasynaptosomal BH4, caused by the intake of exogenous pterin, produced an increase in the dephosphorylation of tyrosine hydroxylase in intact synaptosomes. The effect was rapid and concentration dependent. Moreover, the response appeared to be specific for BH4. A similar and reversible effect was observed with the BH4 precursor sepiapterin, whereas biopterin was virtually inactive. Future studies will continue to address this novel regulatory function with a view to characterizing further the mode of action of BH4 and its biological significance in vivo. Other studies have used rat striatal slices to examine the role of tyrosine hydroxylase in the brain during hyperphenylalanemic states. Specifically, the relative contribution to the protein-bound tyrosine of endogenously formed 3H-tyrosine from exogenous 3H-phenylalanine was compared to that from exogenous l4C-tyrosine. Newly formed 3H-tyrosine incorporation into protein was demonstrated. This 3H-tyrosine incorporation was dependent on the concentration of exogenous 3H-phenylalanine.

我们实验室之前的研究表明，四氢生物蝶呤 (BH4) 在体外激活正弦羟化酶磷酸酶。现在的 结果与这些早期发现一致，表明 BH4 在完整的大鼠纹状体突触体中也有类似的作用。增加 突触体内 BH4，由摄入外源性蝶呤引起，产生 完整酪氨酸羟化酶去磷酸化的增加 突触体。效果迅速且依赖于浓度。而且， 该响应似乎是针对 BH4 的。类似且可逆 使用 BH4 前体七蝶呤观察到效果，而生物蝶呤 几乎不活跃。未来的研究将继续解决这部小说 监管职能，以进一步确定监管模式的特征 BH4 的作用及其体内生物学意义。 其他研究使用大鼠纹状体切片来检查酪氨酸的作用 高苯丙氨酸血症状态下大脑中的羟化酶。具体来说， 对内源性蛋白质结合酪氨酸的相对贡献 将外源 3H-苯丙氨酸形成的 3H-酪氨酸与 来自外源性14C-酪氨酸。新形成的 3H-酪氨酸掺入 蛋白质被证明。这种 3H-酪氨酸的掺入取决于 外源3H-苯丙氨酸的浓度。