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6.2.3.3. Regulatory Action of cyclic AMP
Regulation of glycogenesis and glycogenolysis by hormones 1. Epinephrine, norepinephrine glucagons: Cyclic AMP (cAMP) integrates the regulation of glycogenolysis and glycogenesis. The principal enzymes controlling glycogen metabolism glycogen phosphorylase and glycogen synthase are regulated by a complex series of reactions. cAMP is the intracellular intermediate compound or second messenger through which many hormones act. It if formed from ATP by an enzyme, adenylyl cyclase, occurring in the inner surface of cell membranes. Adenylyl cyclase in activated by hormones such as epinephrine and norepinephrine, acting through β - adrenergic receptors on the cell membrane and additionally in liver by glucagons, acting through an independent glucagon receptor. 2. Insulin cAMP is destroyed by a phosphodiesterase, and it is the activity of this enzyme that maintains the normally low level of cAMP. Insulin increases its activity in liver, thereby lowering the concentration of cAMP. Phosphorylase differs between liver and muscle. In liver the enzyme exists in both an active and an inactive form. Active phosphorylase (phosphorylase a) has one of its serine hydroxy1 groups phosphorylated in an ester linkage. By the action of a specific phosphatase, protein phosphatase-1, the enzyme is in activated to phosphorylase b in a reaction that involves hydrolytic removal of the phosphate from the serine residue. Phosphorylase kinase reactivates it by rephosphorylation with ATP. Pathway of glycogenesis and glycogenolysis in the liver is presented in Fig.6.2.4. |