Effects on Proteoglycan and Glycosaminoglycan Chain Biosynthesis

Induced Effects on Proteoglycan and Glycosaminoglycan Chain Biosynthesis 

The finding some time ago that glycosaminoglycan chains of proteoglycans can be labeled radioactively in vivo and in vitro by use of 

Sections of reviews of the actions of various agents on the processes of connective tissues, etc., are relevant to this discussion (B29, S8, T9). 

Examples of the use of induced biosynthetic effects for the deduction of the processes involved include the use of puromycin and cyclohexi-mide. These compounds, according to experiments with other systems, inhibit protein synthesis. Thus the inhibition of biosynthesis of hyaluronic acid and dermatan sulfate in human fibroblast cultures (M13, M16), of hyaluronic acid in synovial cells (S31), and of chondroitin sulfate (HI) led to the conclusion that the synthesis of protein acceptor is necessary for the polysaccharide chain initiation. Comparison of the effects of 1-butanol on the biosynthesis of chick cartilage chondroitin sulfate and streptococcal hyaluronic acid led to the suggestion that binding of Mg + ions and the uridine diphosphate moiety results in stabilization of the spatial arrangement of the specific enzymes (S47, T4). 

Similar extensive work has been conducted with vitamin A (see T6, and references therein also B29). Experimental deficiency in animals reduces the incorporation of 2-amino-2-deoxy-n-[l- C] glucose and [ S]sulfate into the glycosaminoglycan chains (D16, W16). In this instance the stage of action has been identified, and the effect is due to a block at the first stage of the sulfate activation step (W17, R3, S50). Thus vitamin A is an agent that can activate ATP-sulfurylase and, like L-ascorbic acid, can be an important factor influencing the biosynthetic pathway of the glycosaminoglycans. However, other work 

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Induced Effects on Proteoglycan and Glycosaminoglycan Chain Biosynthesis. 34... 

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