3 ,5 -Cyclic adenyl phosphate

When 3, 5 -cyclic adenylic acid is treated with aqueous sodium hydroxide, the major product that is obtained is 3 -adenylic acid (adenosine 3 -phosphate) rather than 5 -adenyhc acid. Suggest a mechanism that explains the course of this reaction. 

Another hypothesis describing the mode of action of ACTH has recently gained some support. It proposes that ACTH modifies cellular permeability through the intermediate of adenosine-3, 5 -mono-phosphate. The increased penetration of xylose and a-aminoisobutyric acid under the influence of ACTH has been established. It also has been proposed that ACTH stimulates the formation of cyclic adenylate, which in turn induces the synthesis of new mitochondrial proteins. The appearance of the new protein is associated with the development of activity of the enzyme involved in the conversion of cholesterol to pregnenolone. 

Adenosine-3 -monophosphoric acid hydrate [3 -adenylic acid, 3 -AMP] [84-21-9] M 347.3, m 197°(dec, as 2H2O), 210°(dec), m 210°(dec), [a]s46 -50° (c 0.5, 0.5M Na2HP04), pK 3.65, pKz 6.05. It crystallises from large volumes of H2O in needles as the monohydrate, but is not very soluble in boiling H2O. Under acidic conditions it forms an equilibrium mixture of 2 and 3 adenylic acids via the 2, 3 -cyclic phosphate. When heated with 20% HCl it gives a quantitative yield of furfural after 3hours, unlike 5 -adenylic acid which only gives traces of furfural. The yellow monoacridine salt has m 175°(dec) and... 

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. 

Ribonuclease T2 is regarded as a nonspecific endoribonuclease [EC 2.7.7.17, ribonucleate nucleotido-2 -transferase (cyclizing)]. It preferentially splits the internucleotide bonds between the 3 -adenylic acid group and the 5 -hydroxyl group of adjacent nucleotides in RNA, with the intermediary formation of adenosine 2, 3 -cyclic phosphate and splits consequently all secondary phosphate ester bonds of other nucleotides in RNA via the nucleotides 2, 3 -cyclic phopshates. 

Adenosine 2, 3 -cyclic phosphate is scarcely accumulated, though other nucleoside 2, 3 -cyclic phosphates are accumulated as intermediates. This result suggests that the action of RNase T2 on RNA is owing to the cooperation of an adenylic acid specific endonuclease activity and a nonspecific exonuclease activity releasing mononucleotides from the 3 terminal. 

Ribonuclease Ua digestion of ApU has revealed reduced hydrolase activity in the second step of RNase U2 action (30). When 87.4% of ApU was readily degraded to produce uridine and adenosine 2, 3 -cyclic phosphate, no 3 -adenylic acid was detected. After exhaustive degradation of ApU, hydrolysis of adenosine 2, 3 -cyclic phosphate occurred and 3 -adenylic acid gradually appeared. 

Synthesis of cyclic AMP. A catalytic site on adenylate cyclase ( B) removes a proton from the C-3 oxygen, which then attacks the a-phosphate and displaces the pyrophosphate group. This reaction occurs on the inner plasma membrane (see fig. 12.29). 

FIGURE 26-1 Mechanism of action of beta agonists on respiratory smooth muscle. Beta agonists facilitate bronchodilation by stimulating adenyl cyclase activity, which in turn increases intracellular cyclic AMP production. Cyclic AMP activates protein kinase, which appears to add an inhibitory phosphate group to contractile proteins, thus causing muscle relaxation and bronchodilation. 

The regulatory role of calcium ions in intermediary metabolism is well documented. Calcium has been shown to be involved in activation or inhibition of specific enzyme systems [105], For example, it activates cyclic nucleotide phosphodiesterase, phosphofructokinase, fructose 1 6 biphosphatase, glycerol phosphate dehydrogenase, pyruvate dehydrogenase phosphatase and pyruvate dehydrogenase kinase. Calcium ions inhibit pyruvate kinase, pyruvate carboxylase, Na+/K+-AT-Pase and adenylate cyclase. 

Figure 6.1. Adenylate cyclase cataly.ses the formation of cyclic AMP and inorganic phosphate (centre) from ATP (left) cyclic nucleotide phosphodiesterase catalyses the formation of 5 -AMP (right) from cyclic AMP (centre)...

For the assay of adenylate cyclase activity of washed dog heart particles, a medium has been employed which contained 40 mM Tris or 20 mM potassium phosphate buffer (pH 7.5) with 4 mM ATP, 6.6 mM magnesium sulphate, 13 mM caffeine, and 2-5 ixglml of bovine serum albumin in a volume of 1.8 ml [95]. The reaction was stopped by heating the vessels for 3 min in a boiling water bath. After centrifugation, the supernatant fluid was assayed for cyclic AMP by the dog liver phosphorylase-activation method. 

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