METABOLISM OF COMPLEX LIPIDS OF NERVOUS TISSUES

1.C型和D型尼曼综合征患者的代谢缺陷 皮克病已被证明是由于细胞内异常引起的 胆固醇动态平衡。这些疾病中的分子损害 结果：(1)未能下调细胞上的低密度脂蛋白受体 膜；(2)HMGCoA还原酶缺乏下调，这是一个关键 胆固醇生物合成中的酶；以及(3)不能上调- 调节酰基胆固醇酰基辅酶A转移酶，该酶 催化细胞内胆固醇的酯化。测试 用于诊断C型和D型尼曼-皮克病和 杂合子的鉴定和产前诊断 这些条件。 2.其他工作主要集中在合成和使用非 葡萄糖脑苷代谢类似物的研究 高雪病的发病机制及高雪病动物模型的建立 人类的紊乱。一种葡萄糖脑苷的类似物已经被 人工合成的，似乎对选择 缺乏葡萄糖脑苷酶的诱变细胞，这种酶缺乏 在高谢病中。这些细胞将被用来构建一个 转基因类似高谢病的小鼠。

1. The metabolic defect in patients with Types C and D Niemann- Pick disease has been shown to be due to abnormal Intracellular cholesterol homeostasis. The molecular lesion in these disorders results in: (1) failure to down-regulate LDL receptors on cell membranes; (2) lack of down-regulation of HMGCoA reductase, a key enzyme in cholesterol biosynthesis; and (3) inability to up- regulate acyl cholesterol acyl CoA transferase, the enzyme that catalyzes the esterification of intracellular cholesterol. Tests for the diagnosis of Types C and D Niemann-Pick disease and the identification of heterozygotes, and the prenatal diagnosis of these conditions. 2. Other work has centered on the synthesis and use of non- metabolizable analogs of glucocerebroside to examine the pathogenesis of Gaucher's disease and to develop a rodent model of the human disorders. An analog of glucocerebroside has been synthesized that appears to be useful for the selection of mutagenized cells that lack glucocerebrosidase, the enzyme lacking in Gaucher's disease. These cells will be used to construct a transgenic murine analog of Gaucher's disease.