GENETIC DISORDERS OF MAMMALIAN BIOTIN METABOLISM

在初步工作中，我们已经描述了两种不同的遗传（常染色体） 隐性）人生物素代谢紊乱。 在本提案中， 我们扩展了我们对人类生物素代谢缺陷的研究， 生物素依赖性糖尿病的机制和病理生理学的某些问题 遗传病 我们将鉴定和表征生物素 运输，并利用大鼠动物系统来研究生物素在 中枢神经系统 我们将利用某些独特的性质， 突变细胞研究乙酰辅酶A羧化酶的调节， 哺乳动物脂肪酸合成中的限速酶， 调节脂肪酸合成的酶。 这些 机械研究将补充有关扭曲的调查， 脂肪酸代谢的疾病的病理生理学方面 states.

In preliminary work we have characterized two different genetic (autosomal recessive) disorders of human biotin metabolism. In the present proposal we extend our studies of defects in human biotin metabolism, and address certain questions of mechanism and pathophysiology in biotin-dependent genetic diseases. We shall identify and characterize mutants in biotin transport, and utilize a rat animal system to study biotin transport in the central nervous system. We shall exploit certain unique properties of the mutant cells to study the regulation of acetyl CoA carboxylase, a rate-limiting enzyme in mammalian fatty acid synthesis, and the coordinate regulation of the enzymes mediating fatty acid synthesis. These mechanistic studies will complement investigations relating distortions in fatty acid metabolism to aspects of the pathophysiology of the disease states.