The Role of Phosphorylated Dolichols in Membrane Glycoprotein Biosynthesis: Relation to Cholesterol Biosynthesis

Abstract

Publisher Summary The participation of certain phosphorylated long-chain polyisoprenols (dolichols) as saccharide carriers and donors in the biosynthesis of complex carbohydrates has been among the most actively pursued discoveries in the field of membrane biosynthesis and glycoprotein metabolism in the last decade. Dolichols are major long-chain polyisoprenols found in animal cells. They mediate the assembly of asparagine-linked oligosaccharide units of exported and intracellular glycoproteins. This chapter focuses on the animal cell, particularly the cultured vascular smooth muscle cell. The chapter reviews the aspects of glycoprotein structure, the participation of phosphorylated dolichols in glycoprotein biosynthesis, and the interdependent regulation of biosynthesis of phosphorylated dolichols and cholesterol. HMG-CoA reductase is an inducible enzyme that, under steady-state cultural conditions, is in the suppressed state and behaves as a classic nonequilibrium enzyme. It has a rapid turnover rate and its activity is barely detectable in vitro. In some tissues it undergoes covalent modification by phosphorylation/dephosphorylation as a means of modulating its activity. These characteristics of HMG-CoA contribute to its position as a rate-controlling enzyme in polyisoprenol biosynthesis. The increased flux of substrates through this enzyme is useful in discerning regulatory enzymatic steps secondary to the reductase and specific to the pathways of cholesterol or other polyisoprenols such as the dolichols.