3 ,5 -Cyclic adenyl phosphate 3 ,5 -CAMP

Metabotropic receptors, in contrast, create their effects by activating an intracellular G protein. The metabotropic receptors are monomers with seven transmembrane domains. The activated G protein, in turn, may activate an ion channel from an intracellular site. Alternately, G proteins work by activation or inhibition of enzymes that produce intracellular messengers. For example, activation of adenylate cyclase increases production of cyclic adenosine monophosphate (cAMP). Other effector mechanisms include activation of phospholipases, diacylglycerol, creation of inositol phosphates, and production of arachidonic acid products. Ultimately, these cascades can result in protein phosphorylation. 

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. 

A significant contribution to the understanding of hormone action has been recently made by the discovery of the second messenger, adenosine-3, 5 -cyclic phosphate (cAMP) [28,29]. Many hormones, particularly the peptide ones, appear to act primarily at the cell surface where they interact with their specific receptor molecules. Such an interaction of hormone with receptor stimulates the membrane-associated enzyme, adenyl cyclase, which in turn catalyzes the production of intracellular cAMP from ATP [30,31]. Thus, this second messenger, the intracellular cAMP, becomes the mediator of hormone action, and itself regulates gene expression by as-yet-unknown mechanisms. The primary actions of many hormones are thus known, and what remains to be discovered are the actions of cAMP. 

In eukaryotic cells, cyclic AMP is synthesized from ATP by the plasma membrane-bound adenylate cyclase, and modulates, through a cAMP-dependent protein kinase, metabolism and proliferation. A plasma membrane-associated adenylate cyclase from T. brucei has been purified and characterized (45). The enzyme from bloodstream forms has a neutral pH optimum, and kinetic analysis revealed a for ATP of 1.75 mM and a for Mg of 4mM. Inhibition studies indicated no effect with cAMP, but a profound inhibition by PPj, which was competitive with respect to ATP. This observation suggests that the T. brucei adenylate cyclase interacts with the phosphate portion of the ATP molecule, in contrast to adenylate cyclase in rat liver plasma membranes. Other differences between the T. brucei and mammalian adenylate cyclases were observed. For instance, the parasite enzyme activity was not stimulated by glucagon or epinephrine. Furthermore, fluoride, a potent activator of mammalian adenylate cyclase, inhibited the activity of the T. brucei enzyme. 

The 3, 5 -cyclic monophosphate of adenosine (cAMP) (2.148) is an important secondary messenger for intercellular communication in biochemistry. When the cell is stimulated by the first messenger, compound 2.148 is formed from adenosine triphosphate (ATP) (Scheme 2.25). This reaction is catalysed by an adenosine cyclase enzyme. The cAMP then goes on to activate other intracellular enzymes, so producing a cell response. The response is terminated by the hydrolysis of cAMP by phosphodiesterase (a phosphate-ester-hydrolysis enzyme). The action of adenylate cyclase has been mimicked successfully with a p-cyclodextrin complex of Pr(iii) and other lanthanide(iii) metals, under physiological conditions. The... 

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