Degradation phosphorylase

BVdU is degraded by thymidine phosphorylase more rapidly than the natural substrate, thymidine. This rapid enzymic degradation may present a problem in its clinical use. Moreover, herpes vimses develop resistance to BVdU, apparendy because of mutant vimses that have lower thymidine kinase activity. G. D. Seade has dropped further development of BVdU because of increased animal tumor incidence induced by prolonged dosing (1). 

The glycogen phosphorylase reaction degrades glycogen to produce limit dextrins, which are further degraded by debranching enzyme, as already described. 

Secondary signals Glucose 6-phosphate activates synthesis. Ca2+-Calmodulin activates degradation by activating phosphorylase kinase. 

Extending the aforementioned methodology from imidazole to adenine, the Tsuji-Trost reaction between the sodium salt of adenine and allylic acetate 66 gave 67 as a 82 18 mixture of cis trans isomers. Carbocyclic nucleoside 67 was advantageous over normal nucleosides as a drug candidate because it was not susceptible to degradation in vivo by nucleosidases and phosphorylases [52],... 

Since the change in rate of glycogen degradation, catalysed by glycogen phosphorylase, depends on a balance between the two activities, which constimte a cycle, the relationship is also known as an interconversion cycle. By convention, the active form is the a form and the inactive form is the b form (Figure 3.12). 

Scheme 9.5 Multi-step enzymatic process for 2 -deoxyribo-nucleoside production from glucose, acetaldehyde and a nucleobase through glycolysis, reverse reactions of 2 -deoxy-ribonucleoside degradation and ATP regeneration by the yeast glycolytic pathway recycling the phosphate generated by nucleoside phosphorylase.

Figure 6-5. Glycogenolysis. Degradation of glycogen occurs stepwise by hydrolysis of one glucosyl unit at a time from the nonreducing ends by phosphorylase. The limit dextrin occurs as indicated in the second step when there are four glucosyl units remaining to a branch point. Once debranching enzyme has resolved the limit dextrin, degradation by phosphorylase can resume.

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