CHEMISTRY AND METABOLISM OF SPHINGOLIPIDS & GLYCOPROTEIN

拟议的调查是对分布研究的继续， 化学和鞘脂的中间代谢。 这些研究将 主要集中在四个具体领域的努力，鞘脂的生物合成 基础上，开发改进的色谱分析程序， 从鞘糖脂和糖蛋白衍生的碳水化合物，分离和 溶酶体糖基化酶的表征，以及 细胞表面鞘糖脂的同步培养正常和 转化细胞 虽然在这些领域取得了实质性进展 在过去的几年里，仍然需要了解的性质， 鞘氨醇合成酶及其反应的立体化学机理 由这种微粒体酶催化; 细胞的外表面;溶酶体的底物特异性 糖基化酶，这些酶上疏水位点的性质，以及化学性质。 多种形式之间的差异;以及调节细胞周期的因子 膜鞘糖脂的特异性合成和催化， 与真核细胞中的现象如接触抑制有关， 细胞-细胞粘附、细胞表面受体和恶性转化。 在 除了这些项目之外，还提供了分离、定量和 鞘脂的表征和溶酶体糖苷酶的测定 将继续与临床医生合作， 鞘脂代谢错误。

The proposed investigations are a continuation of studies on the distribution, chemistry, and intermediary metabolism of sphingolipids. These studies will focus largely in four specific areas of effort, biosynthesis of sphingolipid bases, development of improved chromatographic procedures for the analysis of carbohydrates derived from glycosphingolipids and glycoproteins, isolation and characterization of lysosomal glycosidases, and control of the metabolism of cell surface glycosphingolipids in synchronized cultures of normal and transformed cells. Although substantial progress has been made in these areas during the past several years, much remains to be learned about the nature of sphingosine synthetase and the stereochemical mechanism of the reaction catalyzed by this microsomal enzyme; the composition of glycosphingolipids on the outer surface of cells; the substrate specificities of lysosomal glycosidases, the nature of hydrophobic sites on these enzymes, and chemical differences between multiple forms; and factors that regulate cell-cycle specific synthesis and catabolism of membrane glycosphingolipids that are associated with phenomena in eukaryotic cells such as contact inhibition, cell-cell adhesion, cell surface receptors, and malignant transformation. In addition to these projects, expertise for the isolation, quantitation and characterization of sphingolipids and for the assay of lysosomal glycosidases will remain available for collaboration with clinicians on potential inborn errors of sphingolipid metabolism.