Cargando…
Genetic defects in dolichol metabolism
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 th...
Autores principales: | , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Netherlands
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281381/ https://www.ncbi.nlm.nih.gov/pubmed/25270028 http://dx.doi.org/10.1007/s10545-014-9760-1 |
_version_ | 1782350986824646656 |
---|---|
author | Buczkowska, Anna Swiezewska, Ewa Lefeber, Dirk J. |
author_facet | Buczkowska, Anna Swiezewska, Ewa Lefeber, Dirk J. |
author_sort | Buczkowska, Anna |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-4281381 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Springer Netherlands |
record_format | MEDLINE/PubMed |
spelling | pubmed-42813812015-01-05 Genetic defects in dolichol metabolism Buczkowska, Anna Swiezewska, Ewa Lefeber, Dirk J. J Inherit Metab Dis Complex Lipids 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. Springer Netherlands 2014-10-01 2015 /pmc/articles/PMC4281381/ /pubmed/25270028 http://dx.doi.org/10.1007/s10545-014-9760-1 Text en © The Author(s) 2014 https://creativecommons.org/licenses/by/4.0/ Open Access This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited. |
spellingShingle | Complex Lipids Buczkowska, Anna Swiezewska, Ewa Lefeber, Dirk J. Genetic defects in dolichol metabolism |
title | Genetic defects in dolichol metabolism |
title_full | Genetic defects in dolichol metabolism |
title_fullStr | Genetic defects in dolichol metabolism |
title_full_unstemmed | Genetic defects in dolichol metabolism |
title_short | Genetic defects in dolichol metabolism |
title_sort | genetic defects in dolichol metabolism |
topic | Complex Lipids |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4281381/ https://www.ncbi.nlm.nih.gov/pubmed/25270028 http://dx.doi.org/10.1007/s10545-014-9760-1 |
work_keys_str_mv | AT buczkowskaanna geneticdefectsindolicholmetabolism AT swiezewskaewa geneticdefectsindolicholmetabolism AT lefeberdirkj geneticdefectsindolicholmetabolism |