Glycogenolysis, control

CycHc adenosine monophosphate (cAMP), produced from ATP, is involved in a large number of ceUular reactions including glycogenolysis, Hpolysis, active transport of amino acids, and synthesis of protein (40). Inorganic phosphate ions are involved in controlling the pH of blood (41). The principal anion of interceUular fluid is HP (Pig. 3) (41). 

Figure 18-8. Coordinated control of glycogenolysis and glycogenesis by cAMP-dependent protein kinase. The reactions that lead to glycogenolysis as a result of an increase in cAMP concentrations are shown with bold arrows, and those that are inhibited by activation of protein phosphatase-1 are shown as broken arrows. The reverse occurs when cAMP concentrations decrease as a result of phosphodiesterase activity, leading to glycogenesis.

Glycogen phosphorylase isoenzymes have been isolated from liver, brain and skeletal muscle. All forms are subject to covalent control with conversion of the inactive forms (GP-b) to the active forms (GP-a) by phosphorylation on specific serine residues. This phosphorylation step, mediated by the enzyme phosphorylase kinase, is initiated by glucagon stimulation of the hepatocyte. Indeed, the same cAMP cascade which inhibits glycogen synthesis simultaneously stimulates glycogenolysis, giving us an excellent example of reciprocal control. 

Four different phosphatases in skeletal muscle catalyze the dephosphorylation of the various enzymes involved in glycogenolysis. Their activities are controlled by various inhibitors. 

Parkhouse, W.S., G.P. Dobson, and P.W. Hochachka (1998). Control of glycogenolysis in rainbow trout muscle during exercise. Can. J. Zool. 66 345-351. 

The glycogenesis and glycogenolysis enzymes subject to hormonal control are glycogen synthase and phosphorylase, respectively. Briefly, glycogen synthase is inhibited by high cellular cAMP and Ca2+ levels, whereas phorphorylase is stimulated. The mechanisms for accomplishing this are quite complex. 

Autonomic outputs. Hypoglycaemia and hypothermia both lead to snstained sympathetic responses. Subjects feel hungry and eat if possible, bnt they refine their other actions to suit the circumstances. Hypoglycaemia requires hepatic glycogenolysis and glnconeogenesis, while hypothermia requires increased heat prodnction and a redistribntion of blood flow. Sympathetic activity is controlled by the hypothalamns, which instrncts the adrenal medulla to secrete adrenalin. This is a rather blunt control, and so localised sympathetic responses (such as blood flow regulation) are mediated by individnal nerves. Parasympathetic activity can also respond to the hypothalamus, which controls the nnclens of the solitary tract. 

Gardemann, A., Stmlik, H., and Jungermann, K. (1987). Nervous control of glycogenolysis and blood flow in arterially and portally perfused liver Am. J. Physiol. 253, E238-E245. 

The Adenylate Cyclase Second Messenger System that Controls Glycogenolysis. 

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