BIOCHEMICAL PATTERNS OF NORMAL AND ABNORMAL PIGMENTATION

色素形成的遗传性疾病是一个医学和心理学问题。 对受影响的个人和社会的负担，但在大多数情况下， 产生色素缺陷的异常尚不清楚， 不可能 黑色素的形成已经在许多物种中进行了研究 在许多组织中，但人体研究一直很困难，因为 缺乏适用于现有人体样本技术。 的 人类色素形成的特征还没有被充分定义 并且对这种疾病的生化和遗传基础没有清楚的了解， 正常和异常色素模式的变化已经发展。 与 在我的实验室开发或正在开发的技术，它现在是 可以进行人体研究。 提案的具体目标 是：1）不同类型的生物化学表征 眼皮肤白化病，2）正常的生化特征 色素模式，和3）色素减退的特点， 普拉德-威利综合征 使用的方法将分析 色素途径，包括：1）酪氨酸酶活性和动力学性质 在酪氨酸、多巴和5，6-二羟基吲哚步骤; 2）酪氨酸酶周转; 3)酪氨酸酶电泳图谱，4）酪氨酸摄取，5）酪氨酸和 血浆和尿液中的途径中间化合物水平; 6）谷胱甘肽 7）多巴色素转换因子和吲哚阻断 因子活性，8）通过电泳、ESR和化学分析黑色素 分析; 9）通过EM的毛球形态学;和10）后的毛干形态学 清理 这些研究将增加我们对人类生物学的理解。 希望这些研究能让不同类型的块 白化病的定义和建议的方法，克服块。

Genetic disorders of pigment formation place a medical and psychological burden on the affected individual and on society, yet in most cases the abnormality producing the pigment defect is unknown and specific therapy is not possible. The formation of melanin has been studied in many species and in many tissues, but human studies have been difficult because of the lack of technique suitable for available human samples. The characterization of human pigment formation has not been adequately defined and no clear understanding of the biochemical and genetic basis for the variations in normal and abnormal pigment patterns has developed. With techniques developed or under development in my laboratory, it is now possible to carry out human studies. The specific aims of the proposal are: 1) the biochemical characterization of the different types of oculocutaneous albinism, 2) the biochemical characterization of normal pigment patterns, and 3) the characterization of the hypopigmentation in the Prader-Willi Syndrome. Methods used will analyze all components of the pigment pathway, including: 1) tyrosinase activity and kinetic properties at the tyrosine, dopa and 5,6-dihydroxyindole step; 2) tyrosinase turnover; 3) tyrosinase electrophoretic pattern, 4) tyrosine uptake, 5) tyrosine and pathway intermediate compound levels in plasma and urine; 6) glutathione levels in hairbulbs; 7) dopachrome conversion factor and indole blocking factor activity, 8) melanin analysis by electrophoresis, ESR, and chemical assay; 9) hairbulb morphology by EM; and 10) hairshaft morphology after clearing. These studies will add to our understanding of human biology. It is hoped that these studies will allow the block in the different types of albinism to be defined and suggest methods for overcoming the block.