Mechanism of activating glycogen breakdown

See also Mechanism of Activating Glycogen Breakdown, Kinase Cascade, Glycogen Breakdown Regulation, Phosphorolysis, Glycogen, Glucose- 1-Phosphate, cAMP... 

See also Calmodulin, Mechanism of Activating Glycogen Breakdown, Glycogen Breakdown... 

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-... 

Possible mechanism for regulation of glycogen metabolism in skeletal muscle by changes in cytosolic calcium. Increased glycogen breakdown may be coordinated with muscle contractions, as indicated here. The actual control scheme is probably more complicated, since phosphoprotein phosphatases are also involved. Interactions with cAMP-activated reactions, which also may complicate regulation, are not included. 

Increased epinephrine activates PKA, which phosphorylates a subunit of PPl and thus reduces the ability of PPl to act on its protein targets. Furthermore, inhibitor 1 is also phosphorylated by PKA so that it too decreases PPl activity, albeit by a different mechanism. Inactivated PPl leads to increased levels of activated (phosphorylated) phosphorylase and inactivated (phosphorylated) glycogen synthase. Glycogen breakdown would be stimulated under these conditions. 

There are two types of cell membrane receptor (a and jS) for adrenaline. -Receptors which are inhibited by -blockers such as propanolol are the main type of receptor in muscle, heart, adipose tissue and many other tissues. They interact with and activate adenylate cyclase in the cell membrane so that the effect of adrenaline on muscle or adipose tissue is to increase the concentration of cAMP in the cell and thus to activate protein kinase. Stimulation of glycogen breakdown by adrenaline in muscle is then mediated by a cascade mechanism similar to that involved in the stimulation of glycogenolysis in liver by glucagon (page 353). Breakdown of triglycerides in adipose tissue, as in liver, occurs as a result of activation of triglyceride lipase by phosphorylation. 

The mechanism of action of glucagon is still unclear. Glucagon also promotes the breakdown of liver glycogen by mobilizing active phosphorylase. As to its peripheral effects, vaHous opinions are held. 

Glycogen phosphorylase b is an enzyme that catalyzes the phospho-lytic breakdown of glycogen to glucose-1-phosphate (Equation 18.11 and Figure 18.17). Crystals of the phosphorylase are catalytically active, but the reaction is too fast to study directly by diffraction methods. A gly-cosylic substrate analogue, heptenitol, is slowly converted to heptulose-2-phosphate, presumably by the same mechanism. 

The catalytic activity of enzymes is controlled in several ways. Reversible allosteric control is especially important. For example, the first reaction in many biosynthetic pathways is allosterically inhibited by the ultimate product of the pathway. The inhibition of aspartate transcarbamoylase by cyti-dine triphosphate (Section 10.1) is a well-understood example of feedback inhibition. This type of control can be almost instantaneous. Another recurring mechanism is reversible covalent modification. For example, glycogen phosphorylase, the enzyme catalyzing the breakdown of glycogen, a storage form of sugar, is activated by phosphorylation of a particular serine residue when glucose is scarce (Section 21.2.1). 

How is glycogen metabolism controiied Gontrol mechanisms ensure that both formation and breakdown of glycogen are not active simultaneously, a situation that would waste energy. 

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