Abstract
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.
Highlights
Heparan sulfate (HS) is a type of glycosaminoglycan (GAG) that contains manyO-(1→4)-linked uronic acid and a glucosamine [1,2]
The core protein of HSPG is biosynthesized in the ribosome followed by translocation to the endoplasmic reticulum (ER) and Golgi, where O-linked attachment of xylose followed by extension of HS takes place (Figure 1A)
Following the formation of linker tetrasaccharide and an extension of glucuronic acid (GlcA) and N-acetylglucosamine (GlcNAc), the modification of HS by sulfation, epimerization, and desulfation modifies the bioactivity of HS (Figure 1B)
Summary
O-(1→4)-linked uronic acid and a glucosamine [1,2]. HS is widely found in tissues, playing an essential role in maintaining cellular function. While these disorders are well-known example includes mucopolysaccharidosis (MPSs), a group of genetic disrare, effective treatments have developed. Mass spectrometric detection has become an increasingly common technique for the quantification of low molecular weight compounds This technique allows us to quantify HS disaccharide species in their intact or derivatized form. Methanolysis may be used for quantification of HS disaccharide [9,10] In this case, the COOH moiety of uronic acid and one glycosylation bond were methylated during the reaction. The COOH moiety of uronic acid and one glycosylation bond were methylated during the reaction Such a technique has been used for the diagnosis of MPS-affected individuals. HS is O-linked through Ser residue to core protein, HSPG (Figure 1) This reaction occurs in the ER and Golgi apparatus. HS species with no sulfation are prominent in dried blood spots, and this is applicable to many tissues [12,13]
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