BIOCHEMICAL PATTERNS OF NORMAL AND ABNORMAL PIGMENTATION

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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.