TETRAHYDROBIOPTERIN BIOSYNTHESIS BY DOPAMINE NEURONS

四氢生物蝶呤是酪氨酸和色氨酸的重要辅因子 羟基酶，生物合成中的限速酶 单胺类神经递质。最近的证据也表明了 四氢生物蝶呤与细胞增殖和分化。的确有 人类单胺类遗传缺陷的确凿证据 神经传递是遗传缺陷的直接结果 四氢生物蝶呤代谢。有暗示的证据表明这些 基因缺陷也可能导致神经发育异常。这 竞争更新概述了一系列广泛的实验，两者都进行了 在培养和活体中，旨在进一步了解 四氢生物蝶呤在儿茶酚胺调节中的作用(S) 儿茶酚胺神经元的生物合成及其发育和可塑性 表型。因为现在很明显，在 四氢生物蝶呤在特定人群中的代谢 儿茶酚胺神经元，这一目标只能通过 对这些差异的本质有一个更全面的了解。 因此，将在多巴胺中研究辅因子代谢的调节。 中枢神经和外周神经中的去甲肾上腺素神经元 在初代组织培养中维护的系统。短期和长期 四氢生物蝶呤与儿茶酚胺生物合成的相互作用 系统将使用组织培养和完整的动物进行研究 这些生物合成系统受到协调调控的期望。 四氢生物蝶呤的发育表达及其可塑性 与儿茶酚胺神经元相关的表型也将被研究。 在组织培养和完整的动物体内。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 发育过程中的生物合成系统和对神经递质的响应 可塑性将在很大程度上取决于对 它们在成熟神经元中的相互作用。希望这些研究能够 最终有助于更好地了解肺炎的病因。 为神经精神障碍的治疗提供不同的方向 本病的治疗方法。

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.