Glycogen metabolic regulation

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)... 

Covalent interconversion of enzymes is well established as a fundamental theme in metabolic regulation. The prototypic reversible interconverting systems include the sequence of phosphorylation/dephosphorylation steps in the activation of mammalian glycogen phosphorylase and pyruvate dehydrogenase as well as the nucleotidyla-tion/denucleotidylation using UTP and ATP in the bacterial glutamine synthetase cascade (see Fig. 1.). 

The multifimctional CaM kinases are collectively referred to as CaM kinases of type II, whereby further subtypes a, p, y and 6 are differentiated. The a and P subtypes of CaM kinase II only occur in the brain whereas the other subtypes are also found in other organs. The multifunctional CaM kinases regulate many processes (see Table 7.1) such as glycogen metabolism, activity of transcription factors, microfilament formation, synaptic release of neurotransmitters from storage vesicles, biosynthesis of neurotransmitters and many more. An important cellular function is assigned to CaM kinase II in brain, where it makes up 0.25 % of the total protein. 

The current state of Ser/Thr phosphorylation of a protein is determined by the relative activity of Ser/Thr-specific protein kinase and protein phosphatase. It is therefore imderstandable that the cell has had to develop special mechanisms to balance the two activities with one another, and, when needed, to allow kinase or phosphatase activity to dominate. One of the best investigated examples of coordinated activity of protein kinases and protein phosphatases is the regulation of glycogen metabolism in skeletal muscle. Glycogen metabolism is an example of how two different signals, namely a cAMP signal and a Ca signal meet in one metabolic pathway and control the activity of one and the same enzyme. 

Fig. 7.18. Regulation of glycogen metabolism in muscle. Phosphorylase kinase stands at the center of regulation of glycogen metabolism. Phosphorylase kinase may exist in an active, phosphorylated form and an inactive, unphosphorylated form. Phosphorylation of phosphorylase kinase is triggered by hormonal signals (e.g. adrenahne) and takes place via an activation of protein kinase A in the cAMP pathway. In the absence of hormonal stimulation, phosphorylase kinase can also be activated by an increase in cytosolic Ca. The active phosphorylase kinase stimulates glycogen degradation and inhibits glycogen synthesis, in that, on the one side, it activates glycogen phosphorylase by phosphorylation, and on the other side, it inactivates glycogen synthase by phosphorylation.

Renewed docking of the catalytic subunit requires the removal of the phosphate residue at the G subunit phosphorylated at the P2 site. This takes place via the protein phosphatases 2A and 2B (calcineurin). Thus, a cascade of protein phosphatases is involved in the regulation of dephosphorylation of key enzymes of glycogen degradation, whereby a phosphatase, namely protein phosphatase I, is indirectly activated by other protein phosphatases. With calcineurin, a Ca -dependent protein phosphatase is involved and thus it is possible to influence glycogen metabolism via Ca -mediated signals. 

Chapter 15 Principles of Metabolic Regulation Glucose and Glycogen... 

In this chapter we look at mechanisms of metabolic regulation, using the pathways in which glucose is an intermediate to illustrate some general principles. First we consider the pathways by which glycogen is synthesized and broken down, a very well-studied case of meta-... 

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