Adenyl cyclase glucagon

Activation of adenylate cyclase Glucagon, adrenocorticotrophical hormone, jS-adrenergic, vasointestinal peptide, adenosine (A2)... 

FIGURE 7.1 Martin Rodbell s conception of the role of the G-protein transducer in the activation of adenylate cyclase by glucagon. (From Birnbaumer, L., FASEB J., 4, 3178, 1990. With permission.)... 

Epinephrine, a hormone made in the adrenal medulla and sympathetic nerve endings, calls for rapid mobilization of energy and glucose. Epinephrine, like glucagon, binds to specific cellular receptors and activates adenylate cyclase. For the most part, epinephrine can be considered... 

Figure 11.6 Initiation of a metabolic response to the binding of glucagon to its receptor. (1) glucagon cell surface receptor (2) G protein (3) adenylate cyclase. (See text for further detail)...

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.

Glucagon is secreted by the a-cells in the Islets of Langerhans in response to a decrease in the concentration of blood glucose. It binds to a receptor in liver and adipose tissue which activates adenyl cyclase and raises the innacel-lular level of cAMP, which activates protein kinase A (Figure 12.13). 

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 ...

All of the effects of the catecholamines bound to (3 adrenergic receptors and of glucagon, ACTH, and many other hormones appear to be mediated by adenylate cyclase. This integral membrane protein catalyzes the formation of cAMP from ATP (Eq. 11-8, step a). The reaction, whose mechanism is considered in Chapter 12, also produces inorganic pyrophosphate. The released cAMP acts as the second messenger and diffuses rapidly throughout the cell to activate the cAMP-dependent protein kinases and thereby to stimulate phosphorylation of a selected group of proteins (Fig. 11-4). Subsequent relaxation to a low level of cytosolic cAMP is accomplished by hydrolysis of the cAMP by a phosphodiesterase (Eq. 11-8, step fr).166/167 jn thg absence of phosphodiesterase cAMP is extremely stable kinetically. However, it is thermodynamically unstable with respect to hydrolysis. 

Occupied receptors for adrenaline, glucagon, ACTH, and histamine activate adenylate cyclase via Gs proteins. Other Gs proteins, which contain subunits designated aolf and which exist as a number of subtypes, mediate olfactory responses. Subunit aD is another specialized polypeptide which is located primarily in neural tissues. A variety of additional G proteins have been discovered in organisms ranging from bacteria to mammals.179 183-186 All have similar structures with 39- to 45-kDa a subunits, 35- to 36-kDa (3 subunits and 5- to 8-kDa y subunits. Whereas the a subunits are unique to each G protein, (3 and y subunits may be shared among several G proteins. These proteins appear to function with many kinds of hormone receptors and... 

Apart from forskolin, a number of other manoyl oxides have been shown to interact with the AC enzyme system. Biotransformation of certain ent- 3-epi-manoy oxides by Curvularia lunata resulted in compounds functionalized in C-3 or in C-3 and C-12, which exhibited an AC stimulatory effect, although milder than that of forskolin (about 30 times less) [173]. The same activity was also ascribed to some synthetic derivatives of en/-8a-hydroxy-13 (16), 14 dien-18-oic acid methyl ester [178,179], The biotransformation of ent-manoyl oxide-16-hydroxy 18-oic acid methyl ester with Rhizopus nigricans, however, resulted in carbomanoyl oxide which showed a selective inhibitory action on the activity of adenylate cyclase depending on the material initially used to stimulate the enzyme. This manoyl oxide inhibited the activity of the enzyme previously stimulated by forskolin but not by glucagon. A manoyl oxide ent-3fi, 6/ -dihydroxy-13-e/ z-manoyl oxide) which also inhibited the activity of AC, was produced from the biotransformation of... 

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,... 

Gs Epinephrine, norepinephrine, histamine, glucagon, ACTH, luteinizing hormone, follicle-stimulating hormone, thyroid-stimulating hormone, and others Adenylate cyclase Ca2+ channels... 

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-... 

The breakdown of fatty acids in (3-oxidation (see Topic K2) is controlled mainly by the concentration of free fatty acids in the blood, which is, in turn, controlled by the hydrolysis rate of triacylglycerols in adipose tissue by hormone-sensitive triacylglycerol lipase. This enzyme is regulated by phosphorylation and dephosphorylation (Fig. 5) in response to hormonally controlled levels of the intracellular second messenger cAMP (see Topic E5). The catabolic hormones glucagon, epinephrine and norepinephrine bind to receptor proteins on the cell surface and increase the levels of cAMP in adipose cells through activation of adenylate cyclase (see Topic E5). The cAMP allosterically activates... 

Fig. 4. Action of thyroid hormones on cyclic AMP production and degradation in the adipocyte. The response of the adipocyte to different lipolytic hormones (/3 catecholamines, ACTH and glucagon) is under thyroid hormone control both at the level of the receptor-adenylate cyclase complex and at the level of the phosphodiesterase. T, also regulates the expression of several key lipogenic enzymes.

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