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: Martin A Thelin, Barbara Bartolini, Jakob Axelsson, Renata Gustafsson, Emil Tykesson, Edgar Pera, Åke Oldberg, Marco Maccarana, Anders Malmstrom
• Journal: The FEBS journal (FEBS J) Vol. 280 Issue 10 Pg. 2431-46 (May 2013) ISSN: 1742-4658 [Electronic] England
• PMID: 23441919 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
• Copyright: © 2013 The Authors Journal compilation © 2013 FEBS.

Chemical References

• Antigens, Neoplasm
• DNA-Binding Proteins
• Neoplasm Proteins
• Dermatan Sulfate
• Iduronic Acid
• Chondroitin Sulfates
• Sulfotransferases
• dermatan-4-sulfotransferase-1
• Carbohydrate Epimerases
• DSE protein, human
• dermatan sulfate epimerase 1, mouse

Topics

• Amino Acid Motifs
• Animals
• Antigens, Neoplasm (genetics, metabolism)
• Carbohydrate Epimerases (genetics, metabolism)
• Carcinoma, Squamous Cell (metabolism, pathology)
• Cell Movement
• Chondroitin Sulfates (metabolism)
• DNA-Binding Proteins (genetics, metabolism)
• Dermatan Sulfate (biosynthesis, metabolism)
• Ehlers-Danlos Syndrome (pathology)
• Extracellular Matrix (metabolism)
• Eye Abnormalities
• Foot Deformities, Congenital (pathology)
• Hand Deformities, Congenital (pathology)
• Humans
• Iduronic Acid (metabolism)
• Joint Instability (congenital)
• Molecular Conformation
• Neoplasm Proteins (genetics, metabolism)
• Skin Abnormalities
• Stem Cells (metabolism)
• Sulfotransferases (genetics, metabolism)
• Thumb (abnormalities, pathology)