Phosphorylase synthesis

The results of our analyses are suiiunarized in Fig. 3. In 3-week-old animals, when the pectoralis weight is the same in broilers and layers, the rate of phosphorylase synthesis is similar in the two strains, at approx 0.1/ day. The strains differ markedly in the rate of degradation of the enzyme broiler, approx 0.01/day, and layer, approx 0.05/day. As the animals grow, the two strains yield very different results. At 8 weeks in the broiler, the synthesis rate declines slightly, to 0.07/day whereas in the layer, it declines to 0.04/day. Thus, the synthesis of the enzyme is not very different in the two strains. By contrast, the rate of degradation of the enzyme declines to 0.005/day in layer, but remains at 0.01/day in the broiler. 

Sircar J. C, Suto M. J, Scott M. E, Dong M. K, Gilbertsen R. B. Inhibitors of human purine nucleoside phosphorylase. Synthesis, purine nucleoside phosphorylase inhibition, and T-cell cytotoxicity of 2,5-diaminothiazolo[5,4-d]pyrimidin-7(6H)-one and 2,5-diaminothiazolo[4,5-d]pyrimidin-7(6H)-one. Two thioisosteres of 8-aminogua-nine, J. Med. Chem. 1986. p. 1804 -1806. DOI 10.1021/jm00159a045... 

Stimulation of glycogen breakdown involves consumption of molecules of ATP at three different steps in the hormone-sensitive adenylyl cyclase cascade (Figure 15.19). Note that the cascade mechanism is a means of chemical amplification, because the binding of just a few molecules of epinephrine or glucagon results in the synthesis of many molecules of cyclic / MP, which, through the action of c/ MP-dependent protein kinase, can activate many more molecules of phosphorylase kinase and even more molecules of phosphorylase. For example, an extracellular level of 10 to 10 M epinephrine prompts the for-... 

Similarly, Ikehara, Tazawa, and Fukui (51) have found that the nucleotides 8-bromo and 8-oxoadenosine 5 -diphosphate, 8-bromo-, 8-oxo, and 8-dimethylaminoguanosine 5 -diphosphate are all inactive as substrates for homopolymer synthesis catalyzed by polynucleotide phosphorylase from Escherichia coli. Some of the results were later confirmed by Kapuler, Monny, and Michelson (52), who found that neither 8-bromo- nor 8-oxoguanosine 5 -diphosphate was active as a substrate for homopolymerization with polynucleotide phosphorylases isolated both irom Azotobacter vinelandii and . coli. 

The breakdown of glycogen to glucose 1-phosphate is catalyzed by phosphorylase. Glycogen synthesis involves a different pathway via uridine diphosphate glucose and glycogen synthase (Figure 18-1). 

C. Oligo- and Poly-nucleotides.—The stepwise enzymatic synthesis of internucleotide bonds has been reviewed. A number of polynucleotides containing modified bases have been synthesised " in the past year from nucleoside triphosphates with the aid of a polymerase enzyme, and the enzymatic synthesis of oligodeoxyribonucleotides using terminal deoxynucleotidyl transferase has been studied. Primer-independent polynucleotide phosphorylase from Micrococcus luteus has been attached to cellulose after the latter has been activated with cyanogen bromide. The preparation of insolubilized enzyme has enabled large quantities of synthetic polynucleotides to be made. The soluble enzyme has been used to prepare various modified polycytidylic acids. ... 

The exact nature of levansucrase activity08 is not clear. It differs in certain respects from invertase, polymerase, fructosaccharase, and phosphorylase. Possibly the aldoside part of the substrate molecule is replaced by an enzyme-linked group, and partial decomposition of this levan precursor to aldose and ketose may furnish the energy necessary for levan synthesis. 

The synthesis of linear 4 —> 1-a-D-glucans from D-glucopyranosyl phosphate by the action of phosphorylases has been shown by comparison of results of methylation and end-group assay and viscosity determination,209 and by potentiometric, iodine titrations82 on the product. The chain length of the enzymic product (100 to 200 D-glucose units) is less than that of the natural component. Whether this is due to impure enzymes cannot yet... 

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

Glycogen and its enzymes are compartmentalized. Glycogen granules are only present in astrocytes of adult animals but are found in both astrocytes and neurons of immature animals. Of the enzymes involved in glycogen metabolism, glycogen phosphorylase is found in astrocytes only. Under steady-state conditions, it is probable that less than 10% of phosphorylase in brain is in the unphosphorylated b form (requiring AMP). This form is probably not very active at the low AMP concentrations present when intracellular glucose is sufficient to maintain ATP synthesis. Brain phosphorylase b kinase is activated indirectly by cAMP and by the molar concentrations... 

McArdle s disease is associated with excessive deposits of glycogen in muscle, and Hers disease with its deposition in liver. In both cases phosphorylase levels in the affected tissues are very low. In spite of this, glycogen synthesis is unimpaired, which is incompatible with glyco-genesis occurring through the action of phosphorylase. 

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