Iduronic acid in chondroitin/dermatan sulfate: biosynthesis and biological function.
The ability of chondroitin/dermatan sulfate (CS/DS) to convey biological information is enriched by the presence of iduronic acid. DS-epimerases 1 and 2 (DS-epi1 and 2), in conjunction with DS-4-O-sulfotransferase 1, are the enzymes responsible for iduronic acid biosynthesis and will be the major focus of this review. CS/DS proteoglycans (CS/DS-PGs) are ubiquitously found in connective tissues, basement membranes, and cell surfaces or are stored intracellularly. Such wide distribution reflects the variety of biological roles in which they are involved, from extracellular matrix organization to regulation of processes such as proliferation, migration, adhesion, and differentiation. They play roles in inflammation, angiogenesis, coagulation, immunity, and wound healing. Such versatility is achieved thanks to their variable composition, both in terms of protein core and the fine structure of the CS/DS chains. Excellent reviews have been published on the collective and individual functions of each CS/DS-PG. This short review presents the biosynthesis and functions of iduronic acid-containing structures, also as revealed by the analysis of the DS-epi1- and 2-deficient mouse models.
Department of Experimental Medical Science, Biomedical Center D12, Lund University, Lund, Sweden.
Anders
A
Malmström
Barbara
B
Bartolini
Martin A
MA
Thelin
Benny
B
Pacheco
Marco
M
Maccarana
D000818:Animals; D055162:Biocatalysis; D001714:Bipolar Disorder / Q000201:enzymology / Q000235:genetics; D002238:Carbohydrate Epimerases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D003871:Dermatan Sulfate / Q000096:biosynthesis / Q000737:chemistry / Q000502:physiology*; D004535:Ehlers-Danlos Syndrome / Q000201:enzymology / Q000235:genetics; D006801:Humans; D007067:Iduronic Acid / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
D003871:Dermatan Sulfate; D007067:Iduronic Acid; D015238:Sulfotransferases; C438013:dermatan-4-sulfotransferase-1; D002238:Carbohydrate Epimerases; C544542:dermatan sulfate epimerase 1, mouse