From glycosylation disorders to dolichol biosynthesis defects: a new class of metabolic diseases
Open Access
- 8 March 2011
- journal article
- review article
- Published by Wiley in Journal of Inherited Metabolic Disease
- Vol. 34 (4), 859-867
- https://doi.org/10.1007/s10545-011-9301-0
Abstract
Polyisoprenoid alcohols are membrane lipids that are present in every cell, conserved from archaea to higher eukaryotes. The most common form, alpha‐saturated polyprenol or dolichol is present in all tissues and most organelle membranes of eukaryotic cells. Dolichol has a well defined role as a lipid carrier for the glycan precursor in the early stages of N‐linked protein glycosylation, which is assembled in the endoplasmic reticulum of all eukaryotic cells. Other glycosylation processes including C‐ and O‐mannosylation, GPI‐anchor biosynthesis and O‐glucosylation also depend on dolichol biosynthesis via the availability of dolichol‐P‐mannose and dolichol‐P‐glucose in the ER. The ubiquity of dolichol in cellular compartments that are not involved in glycosylation raises the possibility of additional functions independent of these protein post‐translational modifications. The molecular basis of several steps involved in the synthesis and the recycling of dolichol and its derivatives is still unknown, which hampers further research into this direction. In this review, we summarize the current knowledge on structural and functional aspects of dolichol metabolites. We will describe the metabolic disorders with a defect in known steps of dolichol biosynthesis and recycling in human and discuss their pathogenic mechanisms. Exploration of the developmental, cellular and biochemical defects associated with these disorders will provide a better understanding of the functions of this lipid class in human.This publication has 70 references indexed in Scilit:
- A novel cerebello-ocular syndrome with abnormal glycosylation due to abnormalities in dolichol metabolismBrain, 2010
- Next generation sequencing in a family with autosomal recessive Kahrizi syndrome (OMIM 612713) reveals a homozygous frameshift mutation in SRD5A3European Journal of Human Genetics, 2010
- Expression of functional bacterial undecaprenyl pyrophosphate synthase in the yeast rer2 mutant and CHO cellsGlycobiology, 2010
- SRD5A3 Is Required for Converting Polyprenol to Dolichol and Is Mutated in a Congenital Glycosylation DisorderCell, 2010
- Deficiency of Dol-P-Man Synthase Subunit DPM3 Bridges the Congenital Disorders of Glycosylation with the DystroglycanopathiesAmerican Journal of Human Genetics, 2009
- Structure and synthesis of polyisoprenoids used in N-glycosylation across the three domains of lifeBiochimica et Biophysica Acta (BBA) - General Subjects, 2009
- A Defect in Dolichol Phosphate Biosynthesis Causes a New Inherited Disorder with Death in Early InfancyAmerican Journal of Human Genetics, 2007
- The Importance of Being DolicholBiochemical and Biophysical Research Communications, 1998
- Isoprenoids in aging and neurodegenerationNeurochemistry International, 1994
- Uptake and modification of dietary polyprenols and dolichols in rat liverFEBS Letters, 1989