Lipid intermediates, glycoprotein biosynthesis

Glycoproteins Fonnd in Plants, Type of Linkage between the Peptide and Saccharide Moieties, and Involvement of Lipid Intermediates in Their Biosynthesis... 

Eukaryotic PNPTs are localized in the membrane of the endoplasmic reticulum (ER) where they catalyze the first step in N-linked glycoprotein biosynthesis resulting in a Dol-PP-GlcNAc intermediate. In contrast, bacterial PNPTs such as WecA, MraY, WbpL, and WbcO utilize different N-acetylhexosamine substrates and they also differ in their susceptibility to selective inhibitors. Several regions of conserved amino acid sequence can be found in bacterial and eukaryotic members of the PNPT family. It is plausible that all the members of this family utilize a common enzymatic mechanism for the formation of the phosphodiester bond. However, bacterial and eukaryotic PNPTs differ in their substrate specificity for various N-acetylhexosamine substrates and also they can discriminate the type of polyisoprenol phosphate. Und-P contains 11 isoprene units all of which are fully unsaturated, while Dol-P can be made of 15-19 isoprene units that have a saturated ct-isoprene. The ct-isoprene is the phosphorylated end of the molecule, which participates in the phosphodiester bond formation with the N-acetylhexosamine-l-P. Therefore, the ability of eukaryotic and bacterial enzymes to exquisitely discriminate their lipid substrate is likely a reflection of evolutionary divergence. 

Glaser, L. Lindsay, B. (1974) The Synthesis of Lipoteichoic Acid Carrier , Biochemical and Biophysical Research Communications, 59, 1131-6 Gold, M.H. Hahn, H.J. (1976) Role of a Mannosyl Lipid Intermediate in the Synthesis of Neurospora crassa Glycoproteins, Biochemistry, 15,1808-14 Goldemberg, S.H. Marechal, L.R. (1963) Biosynthesis of Paramylon in Euglena gracilis, Biochimica et Biophysica Acta, 71, 743-4... 

Biosynthesis of Saccharomyces cerevisiae LK 2G12 Mannan , FEBS Letters, 14,109-13 Sentendreu, R. Lampen, J.O. (1972) Biosynthesis of Mannan in Saccharomyces cerevisiae. Isolation of a lipid Intermediate and its Identification as a Mannosyl-1-phosphoryl Polyprenol , FEBS Letters, 27, 331-4 Sharma, C.B., Babczinski, P., Lehle, L. Tanner, W. (1974) The Role of Dolichol-monophosphate in Glycoprotein Biosynthesis in Saccharomyces cerevisiad, European Journal of Biochemistry, 46, 35-41... 

Japanese Journal of Experimental Mediciney 37, 79-81 Tanner, W. (1969) A Lipid Intermediate in Mannan Biosynthesis in Yeast , Biochemical and Biophysical Research Communications, 35,144-150 Tanner, W., Babczinski, P., Marriott, M., Hasilik, A. Lehle, L. (1979) Glycosylation of Intra- and Extra-cellular Yeast Glycoproteins , Biochemical Society Transactions, 7, 329-31... 

A review of the isolation and separation of phosphatldes and glyco-lipids, by solvent fractionation, preparative column chromatography, and h.p.l.c., has appeared. Lipid X (16) and Lipid Y (17)> rel-ated to lipid A and found in E. coli mutants, have been synthesized. Biologically active monosaccharide Lipid A analogues (18) have been synthesized from the appropriate I -substituted butyl glucosaminide. Reference is made to tri- and tetrasaccharide pyrophosphate esters, intermediates in N-glycoprotein biosynthesis. 

Derivatives of cholesterol which inhibit the biosynthesis of cholesterol in aortic smooth muscle, presumably by suppressing the activity of 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase, also effect a corresponding decrease in the levels of glycosylated lipid intermediates with an apparent inhibition of the biosynthesis of glycoproteins. ... 

Lipid intermediates are formed during the biosynthesis of glycoproteins in microsomes. Column chromatography was used to separate dolichyl D-[ C]mannosyI phosphate from a D-[ C]manno-oligosaccharide which was also bound to lipid after removal of the lipid, the oligosaccharide fraction appeared to be heterogeneous in its reaction with concanavalin A. 

Cholesterol biosynthesis proceeds via the isoprenoids in a multistep pathway. The end product, cholesterol, and the intermediates of the pathway participate in diverse cellular functions. The isoprenoid units give rise to dolichol, CoQ, heme A, isopentenyl-tRNA, famesylated proteins, and vitamin D (in the presence of sunlight and 7-dehydrocholesterol). Dolichol is used in the synthesis of glycoproteins, CoQ in the mitochondrial electron transport chain, famesylation and geranylgeranylation by posttrans-lational lipid modification that is required for membrane association and function of proteins such as p2V and G-protein subunits. 

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