Glycogen synthetase inactive form

Similarly, a complex sequence of steps leads to the synthesis of glycogen (see metabolic regulation, Chapter 16). A protein kinase transforms active glycogen synthetase (I form) into an inactive phosphory-lated form (D form). There are also inactive and active forms of the protein kinase the conversion to the active enzyme is cAMP dependent. It is believed that insulin reduces the level of cAMP and thereby inhibits the protein kinase and the glycogen synthetase [200]. 

Second, GSH functions, presumably nonenzymically, in the reduction of protein thiols which have become oxidized to mixed disulfides (803). In this latter function GSH in some cases converts inactive enzymes to active ones, or vice versa, and may thus serve as a means of metabolic control. Examples of this important possibility are glycogen synthetase D (EC 2.4.1.11) and fructose-1,6-diphosphatase (EC 3.1.3.11). The D form of glycogen synthetase is dependent for activity upon the presence of glucose 6-phosphate. The enzyme is inactivated by GSSG and reactivated by GSH (204). Mixed disulfide formation between thiols of the enzyme and GSSG leads to a decrease in affinity of the enzyme for its activator (205). 

The independent form can be converted into the dependent form by a difiFerent mechanism. It has been found that addition of calcium ions to certain glycogen synthetase preparations produces a conversion of the independent into the dependent form. This conversion does not involve ATP, and is not aflFected by adenosine 3 5 -cyclic phosphate it requires a protein similar to that involved in the activation of inactive phosphorylase b kinase by Ca ". Thus, calcium appears to exert an effect on the regulation of glycogen synthetase, and it is hypothesized that the inactivation of muscle glycogen synthetase after muscle contraction may be caused by this mechanism, mediated by an alteration of intracellular levels of Ca +. 

Glycogen synthetase exists in two forms, called I and D, of which the I form is that normally active. The I, or independent , form of the synthetase is able to transfer glucosyl residues in the absence of glucose-6-phosphate, while the D, or dependent , form is almost inactive without it. Addition of glucose-6-phosphate leads to a great increase in the of the D-form of the enzyme, rather than affecting its for either substrate. 

Glycogen synthetase (11.49) occurs in active unphosphorylated (A) and inactive phosphorylated (B) forms which can be inter-converted by appropriate enzymes. 

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