GLYCOLIPID METABOLISM IN NORMAL AND PATHOLOGICAL TISSUES

拟议研究的近期目标有四个：L。 11日龄β-GalT-4和SAT-3的纯化及动力学研究 鸡脑胚胎。2.纯化和底物专一性 α-FucT-2(GDP-Fuc：nLcOse4Cer(al-2)岩藻糖基转移酶)的研究 牛脾。3.体外生物合成及结构测定 Disialoneolactotetraosylceramide(NeuAc-NeuGc-Gal-GlcNAc-Gal-Glc-Cer)和 牛体内的lacto-N-norhexaosylceramide(Gal-GlcNac-Gal-GlcNac-Gal-Glc-Cer) 脾富含高尔基体膜组分。这些产品的前身是 本实验室从牛红细胞中分离并鉴定。4. 在这项调查的最后阶段，将尝试比较 糖脂：糖基转移酶活性(β-GalT-3， BetaGalT-4和SAT-3)在培养的Tay-Sachs病细胞(转化)中 和非转化)和从Tay-Sachs衍生的亚细胞组分中 脑部病变(尸检)。除了没有溶酶体外 己糖胺酶A-GM2神经节苷脂在Tay-Sachs脑内的蓄积 可能是合成酶严重缺乏的结果 β-GalT-3(UDP-Gal：GM2(β1-3)半乳糖基转移酶)，建议 从我们的前期工作中。(神经鞘糖脂：糖基转移酶 缩写为GSLT)。目前的研究关注的是 神经节苷脂和血型相关神经鞘糖脂的生物合成 正常组织(鸡胚脑和牛脾)和 病理人脑(死后组织)。我们的总体目标是 研究是为了加深对全球可持续发展教育的特殊性的理解。

Immediate objectives of the proposed research are fourfold: l. Purification and kinetic studies of BetaGalT-4 and SAT-3 from 11-day-old embryonic chicken brains. 2. Purification and substrate specificity studies with AlphaFucT-2 (GDP-Fuc:nLcOse4Cer(al-2)fucosyltransferase) from bovine spleen. 3. Biosynthesis in vitro and structure determination of disialoneolactotetraosylceramide(NeuAc-NeuGc-Gal-GlcNAc-Gal-Glc-Cer) and lacto-N-norhexaosylceramide(Gal-GlcNac-Gal-GlcNac-Gal-Glc-Cer) in bovine spleen Golgi-rich membrane fraction. Precursor of these products have been isolated and characterized from bovine erythrocytes in our laboratory. 4. In the final states of this investigation attempts will be made to compare the levels of glycolipid:glycosyltransferase activities (BetaGalT-3, BetaGalT-4, and SAT-3) in cultured Tay-Sachs diseased cells (Transformed and nontransformed) and in the subcellular fractions derived from Tay-Sachs diseased brains (post-mortem). In addition to the absence of lysosomal hexosaminidase A the accumulation of GM2 ganglioside in Tay-Sachs brains could be the result of a severe deficiency of the synthetic enzyme BetaGalT-3 (UDP-Gal:Gm2(Beta1-3)galactosyltransferase), which is suggested from our preliminary work. (The glycosphingolipid: glycosyltransferases are abbreviated as GSLTs). Present studies are concerned with the biosynthesis of gangliosides and blood group-related glycosphingolipids in normal tissues (embryonic chicken brains and bovine spleen) and pathological human brains (post-mortem tissues). The overall goal of our research is to develop an understanding of the specificities of GSLTs.