Key role of dolichol phosphate in glycoprotein biosynthesis.
Studies on the developmental changes in oviducts of hormone-treated chicks and embryos of sea urchins have indicated that the level of dolichol phosphate in the tissues may serve as a control for asparagine-linked glycoprotein biosynthesis. Acute-phase reactant glycoprotein biosynthesis is greatly increased in inflamed rats given a single injection of turpentine. As most of the serum glycoproteins are synthesized via the dolichol pathway, the rate of synthesis of mannosyl and glucosyl dolichol monophosphate and of glucosyl dolichol pyrophosphoryl oligosaccharide, CTP-dependent dolichol phosphokinase, and the level of dolichol phosphate were measured in the livers of inflamed rats. The activities of the glycosyltransferases were increased at least twofold as a result of inflammation. It was also observed that dexamethasone treatment reversed the inflammation-induced increase of mannosyl and glucosyl transfer to dolichol monophosphate. The endogenous level of dolichol phosphate and dolichol kinase activity were increased in microsomes 24 h after inflammation. With exogenous dolichol added to the microsome assay, increased kinase activity was observed as early as 6 h after turpentine injection. The increase of dolichol phosphate in inflammation is most likely due to both greater availability of dolichol and an increase in the level of CTP-dependent dolichol kinase. Studies with purified subcellular fractions showed that dolichol kinase activity is primarily localized in the rough endoplasmic reticular fraction. Since this is the major site of dolichol-phosphate-linked N-glycosylation reactions, a key role of dolichol phosphokinase activity in rough microsomes to initiate the first steps of N-glycoprotein synthesis seems plausible.
D000818:Animals; D003570:Cytidine Triphosphate / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004288:Dolichol Phosphates / Q000032:analysis / Q000378:metabolism*; D006023:Glycoproteins / Q000096:biosynthesis*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D010770:Phosphotransferases / Q000032:analysis; D017853:Phosphotransferases (Alcohol Group Acceptor); D011106:Polyisoprenyl Phosphates / Q000378:metabolism*; D014425:Turpentine / Q000494:pharmacology
D004288:Dolichol Phosphates; D006023:Glycoproteins; D011106:Polyisoprenyl Phosphates; C028306:dolichol monophosphate; D003570:Cytidine Triphosphate; D003907:Dexamethasone; D010770:Phosphotransferases; D017853:Phosphotransferases (Alcohol Group Acceptor); C020087:dolichol kinase; D014425:Turpentine