Distribution, metabolism and function of dolichol and polyprenols |
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Authors: | Jack W. Rip C.Anthony Rupar Kothapalli Ravi Kenneth K. Carroll |
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Affiliation: | * Department of Biochemistry, University of Western Ontario, London, Ontario, Canada N6A 5C1 † Children's Psychiatric Research Institute, P.O. Box 2460, Sanitorium Road, London, Ontario, Canada N6A 4G6 |
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Abstract: | Polyisoprenoid alcohols consisting of 9 or more isoprene units are present in all living cells. They can be fully unsaturated (polyprenols) or alpha-saturated (dolichol). Dolichol forms may have additional saturation at or near the omega-end. Some species contain ony dolichol or only polyprenols while others have nearly equal amounts of both types. Some polyisoprenoid alcohols consist entirely of trans isoprene units but most, including dolichol, contain both trans and cis units. Considerable advances in lipid methodology have occurred since the first review of polyisoprenoid alcohols by Hemming in 1974. For example, direct analysis of both dolichol and Dol-P by HPLC has replaced earlier methods which were often both insensitive and inaccurate. The availability of radiolabeled dolichol and polyprenols has facilitated studies concerning the metabolism and distribution of these compounds. Those studies suggest that only a small portion of the dolichol present in cells is likely to be involved in glycosylation. Polyisoprenoid alcohols are usually present at a family of homologues where each differs in size by one isoprene unit. Little or no size related specificity has been observed for any reaction involving dolichol or polyisoprenol intermediates. The overall length of polyisoprenoid alcohols may, however, affect the manner in which these compounds influence the physical and biochemical properties of membranes. Studies on the biosynthetic pathway leading from cis, trans Pol-PP by phosphatase action. The formation of the dolichol backbone from a polyprenol requires the action of an additional enzyme, an alpha-saturase. This enzyme does not always act at the level of a single common substrate, since Pol-PP, Pol-P, and polyprenol all appear to be utilized as substrates. The major product of the de novo pathway differs among different species. Dol-P would appear to be the most energy efficient end-product since it can participate directly in glycoprotein formation. Most often, however, Dol-P is not the major product of metabolic labeling experiments. In some cases, dolichol is formed so that rephosphorylation is required to provide Dol-P for participation in glycoprotein formation. The kinase responsible for this phosphorylation appears to bypass the considerable stores of dolichol present in tissues (i.e. sea urchin eggs) in favor of dolichol derived directly from de novo synthesis. Although HMGR is a major regulatory component of the pathway leading to polyisoprenoid alcohols and cholesterol, control is most often not co-ordinated.(ABSTRACT TRUNCATED AT 400 WORDS) |
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Keywords: | Asn asparaigne CoA coenzyme A reverse phase packing for HPLC in which 18 carbon fatty acids are linked to silica DES diethylstilbestrol DMAPP dimethylallylpyrophosphate Dol-FA dolichyl fatty acyl ester Dol-P dolichyl phosphate Dol-PP dolichyl pyrophosphate ER endoplasmic reticulum FPP farnesyl pyrophosphate Gal galactose GPP geranyl pyrophosphate GGPP geranyl geranyl pyrophosphate GLC gas-liquid chromatography Glc glucose GlcNac HDL high density lipoprotein HMGCoA 3-hydroxy, 3-methylglutaryl coenzyme A HMGR 3-hydroxy, 3-methylglutaryl CoA reductase HPLC high pressure liquid chromatography IPP isopentenyl pyrophosphate I.R. infrared LDL low density lipoprotein Man mannose MVA mevalonic acid MPP mevalonyl pyrophosphate NMR nuclear magnetic resonance Pol-P polyprenyl phosphate Pol-PP pyprenyl pyrophosphate inorganic pyrophosphate RER rough endoplasmic reticulum SER smooth endoplasmic reticulum TLC thin-layer chromatography |
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