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Review
. 2015 Jan;38(1):157-69.
doi: 10.1007/s10545-014-9760-1. Epub 2014 Oct 1.

Genetic defects in dolichol metabolism

Anna Buczkowska  1 , Ewa Swiezewska, Dirk J Lefeber
Affiliations
Review

Genetic defects in dolichol metabolism

Anna Buczkowska et al. J Inherit Metab Dis. 2015 Jan.

Abstract

Congenital disorders of glycosylation (CDG) comprise a group of inborn errors of metabolism with abnormal glycosylation of proteins and lipids. Patients with defective protein N-glycosylation are identified in routine metabolic screening via analysis of serum transferrin glycosylation. Defects in the assembly of the dolichol linked Glc(3)Man(9)GlcNAc(2) glycan and its transfer to proteins lead to the (partial) absence of complete glycans on proteins. These defects are called CDG-I and are located in the endoplasmic reticulum (ER) or cytoplasm. Defects in the subsequent processing of protein bound glycans result in the presence of truncated glycans on proteins. These defects are called CDG-II and the enzymes involved are located mainly in the Golgi apparatus. In recent years, human defects have been identified in dolichol biosynthesis genes within the group of CDG-I patients. This has increased interest in dolichol metabolism, has resulted in specific recognizable clinical symptoms in CDG-I and has offered new mechanistic insights in dolichol biosynthesis. We here review its biosynthetic pathways, the clinical and biochemical phenotypes in dolichol-related CDG defects, up to the formation of dolichyl-P-mannose (Dol-P-Man), and discuss existing evidence of regulatory networks in dolichol metabolism to provide an outlook on therapeutic strategies.

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Figures

Fig. 1
Fig. 1
Schematic presentation of the enzymatic network leading to production of dolichol and its glycosylated metabolites. Indicated are the biosynthesis-related genes (in italic), glycosylation pathways (gray ovals) and mutations in the genes causative for particular CDGs (gray boxes). All the enzymes involved in the synthesis of dolichol and its glycosylated derivatives are located in the ER or cytoplasm
See this image and copyright information in PMC

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