![]() ![]() Finally, the 6- O and 3- O positions of GlcNAc moities are sulfated by 6- O ( Heparan sulfate 6-O-sulfotransferase) and 3-O (3-OST) sulfotransferases.Ĭhondroitin sulfate and dermatan sulfate, which comprise CSGAGs, are differentiated from each other by the presence of GlcA and IdoA epimers respectively. Next, C-5 uronyl epimerase coverts d-GlcA to l-IdoA followed by 2- O sulfation of the uronic acid sugar by 2- O sulfotransferase ( Heparan sulfate 2-O-sulfotransferase). While elongating, the HSGAG is dynamically modified, first by N-deacetylase, N-sulfotransferase ( NDST1), which is a bifunctional enzyme that cleaves the N-acetyl group from GlcNAc and subsequently sulfates the N-position. With regard to HSGAGs, a multimeric enzyme encoded by EXT1 and EXT2 of the EXT family of genes, transfers both GlcNAc and GlcA for HSGAG chain elongation. Conversely, GalNAc is transferred to the linker by the enzyme GalNAcT to initiate synthesis of CSGAGs, an enzyme which may or may not have distinct activity compared to the GalNAc transferase activity of chondroitin synthase. EXTL2 and EXT元, two genes in the EXT tumor suppressor family, have been shown to have GlcNAcT-I activity. ![]() GlcNAcT-I transfers GlcNAc to the tetrasaccahride linker, which is distinct from glycosyltransferase GlcNAcT-II, the enzyme that is utilized to build HSGAGs. Addition of a GlcNAc promotes the addition of HSGAGs while addition of GalNAc to the tetrasaccharide linker promotes CSGAG development. The first modification of the tetrasaccharide linker determines whether the HSGAGs or CSGAGs will be added. Construction of a tetrasaccharide linker that consists of -GlcAβ1–3Galβ1–3Galβ1–4Xylβ1-O-(Ser)-, where xylosyltransferase, β4-galactosyl transferase (GalTI),β3-galactosyl transferase (GalT-II), and β3-GlcA transferase (GlcAT-I) transfer the four monosaccharides, begins synthesis of the GAG modified protein. HSGAG and CSGAG modified proteoglycans first begin with a consensus Ser-Gly/Ala-X-Gly motif in the core protein. The fourth class of GAG, hyaluronic acid, is synthesized by integral membrane synthases, which immediately secrete the dynamically elongated disaccharide chain. Keratan sulfate may modify core proteins through N-linked glycosylation or O-linked glycosylation of the proteoglycan. Heparin/ heparan sulfate (HSGAGs) and chondroitin sulfate/ dermatan sulfate (CSGAGs) are synthesized in the Golgi apparatus, where protein cores made in the rough endoplasmic reticulum are post-translationally modified via O-linked glycosylation by glycosyltransferases ,forming proteoglycans. GAGs are classified into four groups, based on their core disaccharide structures. This is because GAG synthesis is not template driven, as are proteins or nucleic acids, but constantly altered by processing enzymes. Glycosaminoglycans vary greatly in molecular mass, disaccharide structure, and sulfation. ![]() Mucopolysaccharidoses are a group of metabolic disorders in which abnormal accumulations of glycosaminoglycans occur due to enzyme deficiencies. īecause GAGs are highly polar molecules and attract water the body uses them as lubricants or shock absorbers. GAGs are found in vertebrates, invertebrates and bacteria. The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case of the sulfated glycosaminoglycan keratan, where, in place of the uronic sugar there is a galactose unit. Glycosaminoglycans ( GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. For polysaccharide nomenclature see here. The repeating disaccharide unit (GlcUA(1β→3)GalNAc(1β→4)) n of chondroitin sulfate. ![]() ( July 2015) ( Learn how and when to remove this template message) Please help improve it to make it understandable to non-experts, without removing the technical details. This article may be too technical for most readers to understand. ![]()
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |