Biosynthesis of the Acid Mucopolysaccharides

The principle that tissue constituents are in a state of continuous synthesis and degradation is well established. The rate of turnover of the various constituents of connective tissues varies and, whereas the turnover of collagen is very slow, that of the ground substance is relatively rapid. Although the detailed mechanism of synthesis of the acid mucopolysaccharides is as yet unknown, in a number of instances the general pattern of synthesis has emerged. 

With hyaluronic acid, much of the informative work on its biosynthesis has accrued from studies with bacteria. Group A hemolytic streptococci have long been known (K6) to produce hyaluronic acid identical with that present in mammalian connective tissues. The participation of uridine nucleotides in the biosynthesis of hyaluronic acid is now well 

GNAc-6-phosphate - GNAc-l-phosphate Fig. 1. Possible mechanism of biosynthesis of hyaluronic acid. 

UDP-GNAc -b UDP-GA GNAc-GA-UDP + UDP GNAc-GA-UDP -t- GNAc-GA-UDP GNAc-GA-GNAc-GA-UDP + UDP 

The mechanism of synthesis of hyaluronic acid in mammalian tissues appears to resemble that present in bacteria. The synthesis of hyaluronic acid in tissue culture has been widely studied (GIO, H7), and labeled hyaluronic acid is synthesized in vitro from uniformly labeled D-glucose by explants of human synovial tissue (Yl). An enzyme system has recently been found in mesodermal tissues which catalyzes the synthesis of hyaluronic acid directly from UDP-GNAc and UDP-GA (A5). 

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