Lehrman M A
Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas 75235.
Glycobiology. 1991 Dec;1(6):553-62. doi: 10.1093/glycob/1.6.553.
Asparagine-linked glycosylation is initiated by the synthesis of N-acetylglucosaminylpyrophosphoryl dolichol (GlcNAc-P-P-dolichol), which is extended by a series of glycosyltransferases to yield Glc3Man9GlcNAc2-P-P-dolichol (where Glc is glucose and Man is mannose). The oligosaccharide unit is then transferred en bloc to asparagine residues of nascent polypeptides in the lumen of the rough endoplasmic reticulum. The question here is whether GlcNAc-P-P-dolichol biosynthesis is a fixed process unaffected by cellular events, or a regulated reaction responsive to cellular requirements for glycoprotein biosynthesis. Several lines of evidence indicate that the latter is the case and that GlcNAc-P-P-dolichol biosynthesis may be subject to multiple forms of regulation. Recent information about the N-acetylglucosamine-1-P transferase (GPT) responsible for this reaction and the cloning of cDNA candidates for this enzyme have provided further insight into these mechanisms. This review will examine current hypotheses dealing with GPT and its role in the committed step of asparagine-linked glycosylation.
天冬酰胺连接的糖基化由N-乙酰葡糖胺焦磷酸多萜醇(GlcNAc-P-P-多萜醇)的合成起始,该物质通过一系列糖基转移酶进行延伸,生成Glc3Man9GlcNAc2-P-P-多萜醇(其中Glc为葡萄糖,Man为甘露糖)。然后,寡糖单元作为一个整体转移至糙面内质网腔中新生多肽的天冬酰胺残基上。这里的问题是,GlcNAc-P-P-多萜醇的生物合成是一个不受细胞事件影响的固定过程,还是一个对细胞中糖蛋白生物合成需求有响应的调控反应。有几条证据表明情况是后者,并且GlcNAc-P-P-多萜醇的生物合成可能受到多种形式的调控。有关负责此反应的N-乙酰葡糖胺-1-磷酸转移酶(GPT)的最新信息以及该酶的cDNA候选克隆,为这些机制提供了进一步的见解。本综述将探讨目前关于GPT及其在天冬酰胺连接的糖基化关键步骤中作用的假说。