Cyclic Glucagon

It now appears that many hormones (e.g. glucagon and adrenaline) in both animals and plants exert their effects by, as a first step, decreasing or increasing cyclic AMP within the cell. This may possibly occur by modification of the activity of the enzyme AMP cyclase which generates cyclic AMP from ATP. 

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-... 

Cyclic AMP (cAMP) (Figure 18-5) is formed from ATP by adenylyl cyclase at the inner surface of cell membranes and acts as an intracellular second messenger in response to hormones such as epinephrine, norepinephrine, and glucagon. cAMP is hydrolyzed by phosphodiesterase, so terminating hormone action. In hver, insulin increases the activity of phosphodiesterase. 

Insulin and glucagon regulate gluconeogenesis via changes in cyclic AMP concentration. 

Glucagon stimulates adenylate cyclase activity and this increases the concentration of cyclic AMP. Insulin antagonises this effect via an increase in the activity of cyclic AMP phosphodiesterase, which hydrolyses cyclic AMP to AMP, which results in a decrease in the concentration of cyclic AMP (Figure 6.34). 

Figure 6.34 Effects of glucagon and insulin on the cyclic AMP level. Glucagon increases the activity of adenylate cyclase, which increases the concentration of cyclic AMP whereas insulin activates the phosphodiesterase which hydrolyses cyclic AMP to form AMP. Cyclic AMP activates protein kinase A.

Figure 7.15 Inhibition of acetyl-CoA carboxylase by cyclic AMP dependent protein kinase and AMP dependent protein kinase the dual effect of glucagon. Phosphorylation of acetyl-CoA carboxylase by either or both enzymes inactivates the enzyme which leads to a decrease in concentration of malonyl-CoA, and hence an increase in activity of carnitine palmitoyltransferase-I and hence an increase in fatty acid oxidation. Insulin decreases the cyclic AMP concentration maintaining an active carboxylase and a high level of malonyl-CoA to inhibit fatty acid oxidation.

Figure 12.13 Action and effects of glucagon. Glucagon binds to its receptor on the plasma membrane of the liver which activates adenyl cyclase. The resultant cyclic AMP activates protein kinase which results in phosphorylation and activation of ...

Hypothalamic GHRIF is a cyclic 14 amino-acid peptide, although a 28 amino acid form is also found in some other tissues. GHRIF inhibits the release not only of GH but also of tyrotrophin and corticotrophin from the pituitary, and insulin and glucagon from the pancreas. It can also regulate the level of duodenal secretions. 

Every hormone must have one or more receptors, most of which are proteins. These may be found embedded in the outer surface of the plasma membrane, in the cytoplasm, or in the cell nucleus. Binding of a hormone to its receptor often elicits both a rapid response and a slower one. For example, we have seen that glucagon, adrenaline, and vasopressin bind to cell surface receptors and promote the synthesis of cyclic AMP (Fig. 11-4). Tire cAMP induces rapid chemical modifications of many proteins. Some of these may diffuse into the nucleus and affect transcription of genes, a slower response. Insulin (Chapter 11, Section G) also exerts both rapid and slower responses. 

Cyclic AMP triggers a cascade of reactions that ultimately lead to glycogen breakdown. The immediate action of cAMP is to activate a protein kinase that phosphorylates a number of proteins, including phosphorylase kinase. Phosphorylation of phosphorylase kinase converts it from an inactive to an active form, which catalyzes the conversion of phosphorylase b to phosphorylase a (see chapter 9). The cascade of effects triggered by glucagon is shown in figure 12.29. 

Glucagon and insulin bind to specific receptors on the outer plasma membrane of a target cell. In the case of glucagon, this binding indirectly stimulates the enzyme adenylate cyclase, on the inner surface of the membrane, to catalyze the production of cyclic AMP. Depending on the cell type,... 

Most hormones are released in a cyclic manner (examples include insulin, glucagon, growth hormone, and many... 

Glucagon appears to exert its effects on liver cells by a classic adenyl cyclase-cyclic adenosine monophosphate (cAMP) second messenger system (see Chapter 4).93 Glucagon binds to a specific receptor located on the hepatic cell membrane. This stimulates the activity of the adenyl cyclase enzyme that transforms adeno-... 

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