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Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation
Heparan sulfate (HS) is a type of glycosaminoglycan that plays a key role in a variety of biological functions in neurology, skeletal development, immunology, and tumor metastasis. Biosynthesis of HS is initiated by a link of xylose to Ser residue of HS proteoglycans, followed by the formation of a...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876164/ https://www.ncbi.nlm.nih.gov/pubmed/35216081 http://dx.doi.org/10.3390/ijms23041963 |
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author | Mashima, Ryuichi Okuyama, Torayuki Ohira, Mari |
author_facet | Mashima, Ryuichi Okuyama, Torayuki Ohira, Mari |
author_sort | Mashima, Ryuichi |
collection | PubMed |
description | Heparan sulfate (HS) is a type of glycosaminoglycan that plays a key role in a variety of biological functions in neurology, skeletal development, immunology, and tumor metastasis. Biosynthesis of HS is initiated by a link of xylose to Ser residue of HS proteoglycans, followed by the formation of a linker tetrasaccharide. Then, an extension reaction of HS disaccharide occurs through polymerization of many repetitive units consisting of iduronic acid and N-acetylglucosamine. Subsequently, several modification reactions take place to complete the maturation of HS. The sulfation positions of N-, 2-O-, 6-O-, and 3-O- are all mediated by specific enzymes that may have multiple isozymes. C5-epimerization is facilitated by the epimerase enzyme that converts glucuronic acid to iduronic acid. Once these enzymatic reactions have been completed, the desulfation reaction further modifies HS. Apart from HS biosynthesis, the degradation of HS is largely mediated by the lysosome, an intracellular organelle with acidic pH. Mucopolysaccharidosis is a genetic disorder characterized by an accumulation of glycosaminoglycans in the body associated with neuronal, skeletal, and visceral disorders. Genetically modified animal models have significantly contributed to the understanding of the in vivo role of these enzymes. Their role and potential link to diseases are also discussed. |
format | Online Article Text |
id | pubmed-8876164 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-88761642022-02-26 Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation Mashima, Ryuichi Okuyama, Torayuki Ohira, Mari Int J Mol Sci Review Heparan sulfate (HS) is a type of glycosaminoglycan that plays a key role in a variety of biological functions in neurology, skeletal development, immunology, and tumor metastasis. Biosynthesis of HS is initiated by a link of xylose to Ser residue of HS proteoglycans, followed by the formation of a linker tetrasaccharide. Then, an extension reaction of HS disaccharide occurs through polymerization of many repetitive units consisting of iduronic acid and N-acetylglucosamine. Subsequently, several modification reactions take place to complete the maturation of HS. The sulfation positions of N-, 2-O-, 6-O-, and 3-O- are all mediated by specific enzymes that may have multiple isozymes. C5-epimerization is facilitated by the epimerase enzyme that converts glucuronic acid to iduronic acid. Once these enzymatic reactions have been completed, the desulfation reaction further modifies HS. Apart from HS biosynthesis, the degradation of HS is largely mediated by the lysosome, an intracellular organelle with acidic pH. Mucopolysaccharidosis is a genetic disorder characterized by an accumulation of glycosaminoglycans in the body associated with neuronal, skeletal, and visceral disorders. Genetically modified animal models have significantly contributed to the understanding of the in vivo role of these enzymes. Their role and potential link to diseases are also discussed. MDPI 2022-02-10 /pmc/articles/PMC8876164/ /pubmed/35216081 http://dx.doi.org/10.3390/ijms23041963 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Review Mashima, Ryuichi Okuyama, Torayuki Ohira, Mari Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation |
title | Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation |
title_full | Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation |
title_fullStr | Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation |
title_full_unstemmed | Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation |
title_short | Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation |
title_sort | physiology and pathophysiology of heparan sulfate in animal models: its biosynthesis and degradation |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876164/ https://www.ncbi.nlm.nih.gov/pubmed/35216081 http://dx.doi.org/10.3390/ijms23041963 |
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