Phosphorylase metabolism

FIG. 1. Interrelationships between vitamin B6 and phosphorylase metabolism. The low rate of turnover of glycogen phosphorylase (gpb) and the lack of exchange of free and protein-bound PLP mean that exchange into the muscle pool is largely controlled by the kinetics of turnover of the enzyme. At present, it is not known whether resolution of the holo-enzyme is a prerequisite or consequence of phosphorylase degradation. Reproduced with permission of llie Biochemical Journal. 

The principal enzymes controlling glycogen metabolism—glycogen phosphorylase and glycogen synthase— are regulated by allosteric mechanisms and covalent modifications due to reversible phosphorylation and... 

REGULATION OF GLYCOGEN METABOLISM IS EFFECTED BY A BALANCE IN ACTIVITIES BETWEEN GLYCOGEN SYNTHASE PHOSPHORYLASE (Figure 18-8)... 

The biosynthesis of purines and pyrimidines is stringently regulated and coordinated by feedback mechanisms that ensure their production in quantities and at times appropriate to varying physiologic demand. Genetic diseases of purine metabolism include gout, Lesch-Nyhan syndrome, adenosine deaminase deficiency, and purine nucleoside phosphorylase deficiency. By contrast, apart from the orotic acidurias, there are few clinically significant disorders of pyrimidine catabolism. 

Be Pyridoxine, pyridoxal, pyridoxamine Coenzyme in transamination and decarboxylation of amino acids and glycogen phosphorylase role in steroid hormone action Disorders of amino acid metabolism, convulsions... 

Pyridoxal phosphate is a coenzyme for many enzymes involved in amino acid metabolism, especially in transamination and decarboxylation. It is also the cofactor of glycogen phosphorylase, where the phosphate group is catalytically important. In addition, vitamin Bg is important in steroid hormone action where it removes the hormone-receptor complex from DNA binding, terminating the action of the hormones. In vitamin Bg deficiency, this results in increased sensitivity to the actions of low concentrations of estrogens, androgens, cortisol, and vitamin D. 

Pantothenic acid is present in coenzyme A and acyl carrier protein, which act as carriers for acyl groups in metabolic reactions. Pyridoxine, as pyridoxal phosphate, is the coenzyme for several enzymes of amino acid metabolism, including the aminotransferases, and of glycogen phosphorylase. Biotin is the coenzyme for several carboxylase enzymes. 

H4. Hershfield, M. S., and Mitchell, B. S., Immunodeficiency diseases caused by adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency. In Metabolic and Molecular Bases of Inherited Disease, 7th ed. (C. R. Scriver, A. L. Beaudet, W. S. Sly, and D. Valle, eds.), pp. 1725-1768. McGraw-Hill, New York, 1995. 

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... 

As is often the case, tissue-specific control mechanisms operate to optimise adaptation to particular conditions. For example, muscle contraction requires an increase in cytosolic calcium ion concentration (see Section 7.2.1, Figure 7.4). During exercise when energy generation needs to be increased, or from a more accurate metabolic point of view, when the ATP-to-ADP ratio falls rapidly, and the accompanying rise in [Ca2 + ] activate (i) glycogen phosphorylase which initates catabolism of... 

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