The glucuronyl C5-epimerase activity is the limiting factor in the dermatan sulfate biosynthesis

An early step in the biosynthesis of dermatan sulfate is polymerization to chondroitin, which then is modified by the D-glucuronyl C5-epimerase and ma inly 4-O-sulfotransferase. The final structure of the dermatan sulfate side chains varies and our aim was to identify, which of the two enzymes that a re crucial to generate dermatan sulfate copolymeric structures in tissues. Dermatan sulfate side chains of biglycan and decorin were prepared from fib roblasts and nasal and articular chondrocytes and characterized regarding d etailed structure. Microsomes were prepared from these cells and the activi ties of D-glucuronyl C5-epimerase and 4-O-sulfotransferase were determined. Chondrocytes from nasal cartilage synthesized biglycan and decorin contain ing 10%, articular chondrocytes 20-30%, and fibroblast 80% of the uronosyl residues in the L-iduronyl configuration. All three tissues contained high amount of 4-O-sulfotransferase activity. The activity of D-glucuronyl C5-ep imerase showed different relationships. Fibroblasts contained a high level of the epimerase activity, articular chondrocytes intermediary activity, an d in nasal cartilage it was barely detectable. The data indicate that the a ctivity of the D-glucuronyl C5-epimerase is the main factor for formation o f dermatan sulfate in tissues. (C) 2001 Academic Press.