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...
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MDPI AG
2022-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/4/1963 |
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| author | Ryuichi Mashima Torayuki Okuyama Mari Ohira |
| author_facet | Ryuichi Mashima Torayuki Okuyama Mari Ohira |
| author_sort | Ryuichi Mashima |
| collection | DOAJ |
| 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 <i>N</i>-acetylglucosamine. Subsequently, several modification reactions take place to complete the maturation of HS. The sulfation positions of <i>N</i>-, 2-<i>O</i>-, 6-<i>O</i>-, and 3-<i>O</i>- 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. |
| first_indexed | 2024-03-09T21:45:37Z |
| format | Article |
| id | doaj.art-0247c37bb8f848379d8c7cbb1e9e7eaf |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T21:45:37Z |
| publishDate | 2022-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0247c37bb8f848379d8c7cbb1e9e7eaf2023-11-23T20:17:27ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-02-01234196310.3390/ijms23041963Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and DegradationRyuichi Mashima0Torayuki Okuyama1Mari Ohira2Department of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, JapanDepartment of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, JapanDepartment of Clinical Laboratory Medicine, National Center for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, JapanHeparan 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 <i>N</i>-acetylglucosamine. Subsequently, several modification reactions take place to complete the maturation of HS. The sulfation positions of <i>N</i>-, 2-<i>O</i>-, 6-<i>O</i>-, and 3-<i>O</i>- 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.https://www.mdpi.com/1422-0067/23/4/1963heparan sulfateknockout micebiosynthesislysosome |
| spellingShingle | Ryuichi Mashima Torayuki Okuyama Mari Ohira Physiology and Pathophysiology of Heparan Sulfate in Animal Models: Its Biosynthesis and Degradation International Journal of Molecular Sciences heparan sulfate knockout mice biosynthesis lysosome |
| 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 | heparan sulfate knockout mice biosynthesis lysosome |
| url | https://www.mdpi.com/1422-0067/23/4/1963 |
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