Enzymes Adenylate cyclase

Forskolin is an activator of the enzyme adenylate cyclase which has therapeutic utility. Outlined below are stereocontrolled routes to racemic and natural chiral forms of forskolin derived by multistrategic retrosynthedc analysis. 

FIGURE 2.6 Production of cyclic AMP from ATP by the enzyme adenylate cyclase. Cyclic AMP is a ubiquitous second messenger in cells activating numerous cellular pathways. The adenylate cyclase is activated by the a subunit of Gs-protein and inhibited by the a-subunit of Gj-protein. Cyclic AMP is degraded by phosphodiesterases in the cell. 

Prostacyclin and its analogues also function by increasing the level of platelet cAMP, presumably by activation of the enzyme adenyl cyclase. A chemically stable analogue of prostacyclin called Iloprost has been effective in preventing consumption of platelets (71). 

In Graves disease, hyperthyroidism results from the action of thyroid-stimulating antibodies (TSAb) directed against the thyrotropin receptor on the surface of the thyroid cell. These immunoglobulin G antibodies bind to the receptor and activate the enzyme adenylate cyclase in the same manner as TSH. 

Selective sympathomimetics cause relaxation of bronchial smooth muscle and bronchodilation by stimulating the enzyme adenyl cyclase to increase the formation of cyclic adenosine monophosphate. They may also improve mucociliary clearance. 

The nucleotide cyclic AMP (3, 5 -cyclic adenosine monophosphate, cAMP) is a cyclic phosphate ester of particular biochemical significance. It is formed from the triester ATP by the action of the enzyme adenylate cyclase, via nucleophilic attack of the ribose 3 -hydroxyl onto the nearest P=0 group, displacing diphosphate as leaving group. It is subsequently inactivated by hydrolysis to 5 -AMP through the action of a phosphodiesterase enzyme. 

Theoretical explanations for the stimulatory activity of the methyl xanthines. These compounds inhibit phosphodiesterase reaulting in the prolonged activ of metabolic enzymes.Adenylate cyclase activity is modulated by the bindin free adenosine. The methyl xanthines are antagonists to adenosine but the bindings do not produce its modulating (inhibitory, attenuating) response. Therefore the end result is stimulatory in relation to cAMP activity. 

Cyclic-AMP is formed from ATP in a reaction catalyzed by the enzyme adenylate cyclase. Assume that adenylate cyclase acts as a base to remove a proton from the 3 -hydroxyl group of ATP and write a mechanism for the formation of cAMP. 

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,... 

The observation that victims of the Japanese Minamata disaster had suffered considerable damage to plasma membranes has led to investigation of possible reaction mechanisms whereby such damage may result from MeHg+ poisoning. It has been demonstrated that methylmercury is the most potent inhibitor of the enzyme adenyl cyclase yet reported.284 The enzyme occurs in liver plasma membranes and plays a part in the metabolism of mammalian cells. 

When epinephrine binds to cells, it stays outside on the membrane-bound receptor. The second messenger, cyclic AMP, is made by the enzyme adenylate cyclase. 

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