title: Biological functions of iduronic acid in chondroitin/dermatan sulfate.
abstract: The presence of iduronic acid in chondroitin/dermatan sulfate changes the properties of the polysaccharides because it generates a more flexible chain with increased binding potentials. Iduronic acid in chondroitin/dermatan sulfate influences multiple cellular properties, such as migration, proliferation, differentiation, angiogenesis and the regulation of cytokine/growth factor activities. Under pathological conditions such as wound healing, inflammation and cancer, iduronic acid has diverse regulatory functions. Iduronic acid is formed by two epimerases (i.e. dermatan sulfate epimerase 1 and 2) that have different tissue distribution and properties. The role of iduronic acid in chondroitin/dermatan sulfate is highlighted by the vast changes in connective tissue features in patients with a new type of Ehler-Danlos syndrome: adducted thumb-clubfoot syndrome. Future research aims to understand the roles of the two epimerases and their interplay with the sulfotransferases involved in chondroitin sulfate/dermatan sulfate biosynthesis. Furthermore, a better definition of chondroitin/dermatan sulfate functions using different knockout models is needed. In this review, we focus on the two enzymes responsible for iduronic acid formation, as well as the role of iduronic acid in health and disease.
authors: Department of Experimental Medical Science, BMC, Lund University, Sweden.
authors: Martin A
authors: MA
authors: Thelin
authors: Barbara
authors: B
authors: Bartolini
authors: Jakob
authors: J
authors: Axelsson
authors: Renata
authors: R
authors: Gustafsson
authors: Emil
authors: E
authors: Tykesson
authors: Edgar
authors: E
authors: Pera
authors: Åke
authors: Å
authors: Oldberg
authors: Marco
authors: M
authors: Maccarana
authors: Anders
authors: A
authors: Malmstrom
mesh_terms: D020816:Amino Acid Motifs; D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism*; D002238:Carbohydrate Epimerases / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002809:Chondroitin Sulfates / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D003871:Dermatan Sulfate / Q000096:biosynthesis / Q000378:metabolism*; D004535:Ehlers-Danlos Syndrome / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005124:Eye Abnormalities; D005532:Foot Deformities, Congenital / Q000473:pathology; D006228:Hand Deformities, Congenital / Q000473:pathology; D006801:Humans; D007067:Iduronic Acid / Q000378:metabolism*; D007593:Joint Instability / Q000151:congenital; D008968:Molecular Conformation; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D012868:Skin Abnormalities; D013234:Stem Cells / Q000378:metabolism; D015238:Sulfotransferases / Q000235:genetics / Q000378:metabolism; D013933:Thumb / Q000002:abnormalities / Q000473:pathology
chemical_list: D000951:Antigens, Neoplasm; D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D003871:Dermatan Sulfate; D007067:Iduronic Acid; D002809:Chondroitin Sulfates; D015238:Sulfotransferases; C438013:dermatan-4-sulfotransferase-1; D002238:Carbohydrate Epimerases; C405383:DSE protein, human; C544542:dermatan sulfate epimerase 1, mouse