Phosphorylation glycogen

Pyridoxine is involved as a co-factor coenzyme in about 100 enzyme systems. Thus, in addition to the reactions mentioned above, it is required for glycogen phosphoryl-ase, which catalyses the release of glucose from stored glycogen, haemoglobin biosynthesis, the generation of glucose from amino acids (gluconeogenesis), the biosynthesis of niacin from tryptophan and nucleic add biosynthesis. 

Muscle glycogen phosphorylase is a dimer of two identical subunits (842 residues, 97.44 kD). Each subunit contains a pyridoxal phosphate cofactor, covalently linked as a Schiff base to Lys °. Each subunit contains an active site (at the center of the subunit) and an allosteric effector site near the subunit interface (Eigure 15.15). In addition, a regulatory phosphorylation site is located at Ser on each subunit. A glycogen-binding site on each subunit facilitates prior association of glycogen phosphorylase with its substrate and also exerts regulatory control on the enzymatic reaction. 

As early as 1938, it was known that glycogen phosphorylase existed in two forms the less active phosphorylase b and the more active phosphorylase a. In 1956, Edwin Krebs and Edmond Eischer reported that a converting enzyme could convert phosphorylase b to phosphorylase a. Three years later, Krebs and Eischer demonstrated that the conversion of phosphorylase b to phosphorylase a involved covalent phosphorylation, as in Eigure 15.17. 

Glycogen synthase also exists in two distinct forms which can be interconverted by the action of specific enzymes active, dephosphorylated glycogen synthase I (glucose-6-P-independent) and less active phosphorylated glycogen synthase D (glucose-6-P-dependent). The nature of phosphorylation is more complex with glycogen synthase. As many as nine serine residues on the enzyme appear to be subject to phosphorylation, each site s phosphorylation having some effect on enzyme activity. 

Huang, D., Wilson, W. A., and Roach, P. J., 1997. Glucose-6-P control of glycogen syndiase phosphorylation in yeast. Journal of Biological Chemistry 272 22495-22501. 

Johnson, L. N., 1992. Glycogen phosphorylase Control by phosphorylation and allosteric effectors. FASEB Journal 6 2274-2282. 

GSK3 phosphorylates glycogen synthase (GS), the key enzyme for glycogen synthesis which builds up the... 

Liver Activation of glycogen synthesis Activation of glycogen synthase (GS) Inactivation of glycogen synthase kinase 3 (GSK3) through phosphorylation by Akt... 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

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

Like phosphorylase, glycogen synthase exists in either a phosphorylated or nonphosphorylated state. However, unlike phosphorylase, the active form is dephosphorylated (glycogen synthase a) and may be inactivated to... 

The ATP required as the constant energy source for the contraction-relaxation cycle of muscle can be generated (1) by glycolysis, using blood glucose or muscle glycogen, (2) by oxidative phosphorylation, (3) from creatine... 

Another substrate of PKB is glycogen synthase kinase 3(5 (GSK3(5), whose phosphorylation causes its inactivation. As its name indicates, this protein kinase was originally discovered as a regulator... 

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