TETRAHYDROBIOPTERIN BIOSYNTHESIS BY DOPAMINE NEURONS

四氢生物蝶呤是酪氨酸和色氨酸的必需辅助因子 羟化酶，在生物合成的限速酶， 单胺类神经递质最近的证据也表明， 四氢生物蝶呤在细胞增殖和分化中的作用。有 人类单胺遗传缺陷的明确证据 神经传递的遗传缺陷的直接结果， 四氢生物蝶呤代谢有证据表明，这些 遗传缺陷也可能导致神经发育异常。这 竞争性更新概述了一系列广泛的实验， 在培养和体内，旨在进一步了解 四氢生物蝶呤在调节儿茶酚胺中的作用 生物合成与儿茶酚胺神经元的发育和可塑性 表型因为现在很明显， 四氢生物蝶呤在特定人群中的代谢 在神经元中，这一目标只能通过以下方式实现： 更全面地了解这些差异的本质。 因此，将在多巴胺和多巴胺受体中研究辅因子代谢的调节。 来自中枢和外周神经的含去甲肾上腺素的神经元 在原代组织培养中维持的系统。短期和长期范围 四氢生物蝶呤与儿茶酚胺生物合成相互作用 系统将使用组织培养和完整动物进行研究， 期望这些生物合成系统受到协调调节。 四氢生物蝶呤的发育表达及其可塑性 表型，因为它涉及到儿茶酚胺神经元也将进行研究 在组织培养和完整的动物中。这些目标是相互关联的， 儿茶酚胺与辅因子相互作用的解释 生物合成系统在发展和响应神经递质 可塑性将高度依赖于进一步表征 它们在成熟神经元中的相互作用。希望这些研究将 最终有助于更好地了解 神经精神疾病，并提供不同的方向， 在其治疗方法。

Tetrahydrobiopterin is the essential cofactor for tyrosine and tryptophan hydroxylases, the rate-limiting enzymes in the biosynthesis of the monoamine neurotransmitters. Recent evidence also suggests roles for tetrahydrobiopterin in cell proliferation and differentiation. There is unequivocal evidence of inherited deficiencies in human monoamine neurotransmission which are the direct result of genetic defects in tetrahydrobiopterin metabolism. There is suggestive evidence that these genetic defects might also result in abnormal neural development. This competitive renewal outlines a broad series of experiments performed both in culture and in vivo which are designed to further the understanding of the role(s) of tetrahydrobiopterin in the regulation of catecholamine biosynthesis and the development and plasticity of the catecholamine neuron phenotype. Since it is now apparent that there are important differences in the metabolism of tetrahydrobiopterin across specific populations of catecholamine neurons, this objective can only be accomplished by first obtaining a more complete understanding of the nature of these differences. The regulation of cofactor metabolism will thus be studied in dopamine and norepinephrine-containing neurons from the central and peripheral nervous systems maintained in primary tissue culture. The short and long-term interaction between tetrahydrobiopterin and catecholamine biosynthetic systems will be investigated using tissue culture and intact animals with the expectation that these biosynthetic systems are coordinately regulated. The developmental expression and plasticity of the tetrahydrobiopterin phenotype as it relates to catecholamine neurons will also be investigated in tissue culture and in the intact animal. These goals are related in that the interpretation of the interaction between catecholamine and cofactor biosynthetic systems during development and in response to neurotransmitter plasticity will be highly dependent upon the further characterization of their interaction in the mature neuron. It is hoped that these studies will ultimately aid in a better understanding of the etiology of neuropsychiatric disorders and provide different directions for therapeutic approaches in its treatment.