AMP synthesis

H2 receptors are intronless GPCRs linked to G, proteins and cyclic AMP synthesis 256... 

Since Nirenberg and his collaborators (5,6,11) have reported that in NG108-15 cells, opiates produce an initial inhibition of cyclic AMP synthesis (0 to 30 min), followed by a period in which the cell adjusts and cyclic AMP levels return to normal (lO -30 hrs), and finally a period where cyclic AMP levels are elevated (when the drug is removed or metabolized supposed withdrawal) it was of interest to follow the time-course of the inhibition. 

Catabolite repression is a two-part system. The first component is the small-molecule regulator, cyclic AMP. Glucose decreases cyclic AMP synthesis. The second component is cyclic AMP binding protein, CAP. CAP binds cAMP and thereby helps RNA polymerase bind to the promoter. When bound to cAMP, CAP binds to a sequence at the 5 end of the lac promoter. CAP binding bends the DNA, allowing protein-protein contact between CAP and polymerase. It therefore behaves in the opposite manner of repressor. Repressor (LacI) binds to operator DNA only in the absence of its small-molecule ligand, while CAP binds to promoter DNA in the presence of its small-molecule ligand. 

Y. Yamagata, H. Inoue and K. Inomata (1995). Specific effect of magnesium ion on 2, 3 -cyclic AMP synthesis from adenosine and trimetaphosphate in aqueous solution. Origin Life Evol. Biosph., 25, 47-52. 

In plasma membrane preparations, binding of ACTH to its receptor activates adenylate cyclase. In common with other receptors which activate adenylate cyclase, the interaction of ACTH with adenylate cyclase appears to require the action of a G-protein, presumably Gs, since ACTH stimulation of cyclic AMP synthesis in plasma membrane preparations is enhanced by GTP, by non-hydrolysable GTP... 

The 7-Thia-prostanoid with the natural configuration of all chiral centers, 24, stimulates the c-AMP synthesis in the mouse ovary, whereas 25, which possesses... 

P-adrenergic blockade. There is increased tissue sensitivity to catecholamines in h) erth5Toidism with an increase in either the number of 3-adrenoceptors or the second messenger response (i.e. intracellular cyclic AMP synthesis) to their stimulation. Therefore some of the xmpleasant symptoms are adrenergic. 

In the first step of AMP synthesis, the C-6 keto oxygen of the hypoxanthine base moiety of IMP is replaced by the amino group of aspartate. In the second step the product of the first reaction, adenylosuccinate, is hydrolyzed to form AMP and fumarate. GMP synthesis begins with the oxidation of IMP to form XMP. GMP is produced as the amide nitrogen of glutamine replaces the C-2 keto oxygen of XMP. Note that AMP formation requires GTP and GMP formation requires ATP. 

Feedback inhibition is indicated by red arrows. The stimulation of AMP synthesis by GTP and GMP synthesis by ATP ensures a balanced synthesis of both families of purine nucleotides. 

Trace the following radiolabeled molecule through the biosynthetic route to AMP synthesis. 

Fructose 1,6 bisphosphatase - The primary regulatory enzyme for gluconeogenesis. Inactivated potently by F2,6BP (See Figure 16.17) and AMP. Synthesis of the enzyme is sensitive to hormonal control. 

The 5-ITT and 5-HTj receptors also couple to G -adenylyl cyclase their affinity for clozapine may relate to its antipsychotic efficacy (see Chapters 11 and 18). Of the two subtypes of 5-HT receptors, the 5-HT receptor seems to inhibit cyclic AMP synthesis, while 5-HT receptor-effector coupling has not been described. 

AMP synthesis (The two reactions of AMP synthesis minic steps in the purine pathway leading to IMP.) In Step 1, the 6-0 of inosine is displaced by aspartate to yield adenylosuccinate. The energy required to drive this reaction is derived from GTP hydrolysis. The enzyme is adenylosuccinate synthetase. 

Paralleling membrane studies, forskolln elicits Increases In Intracellular cyclic AMP In the eye- mutants of the S49 lymphoma cell line which are about ten-fold less than the Increase elicited in wild type S49 lymphoma cellsSimilar results are seen in the H21a mutant which contains a lesion In Ns impairing Its coupling to the catalytic subunit. A maximal stimulation of cyclic AMP synthesis by forskolln in S49 cells requires the presence of a functional Ns protein. 

Forskolln stimulation of cyclic AMP synthesis in C6-2B rat astrocytoma cells is decreased after the cells are grown In the presence of cyclohexlmide, a protein synthesis inhibitor. 0 This occurs without the loss of isoproterenol or cholera toxin stimulated adenylate cyclase. It was suggested that the cyclohexlmide blocks the synthesis of a protein which has a high turnover rate and is required for forskolln stimulation of adenylate cyclase. 

In another direction one must consider that adenosine accumulation could lead to other biochemical effects. It has been known for some time that adenosine can stimulate cyclic AMP synthesis in brain slices... 

A. Regulation of Adenylosuccinate Synthetase with Respect to AMP Synthesis and Interconversion... 

Regulation in tumor cells appears to allow more efficient conversion of IMP to AMP. The level of the synthetase is increased from 1.6- to 3.7-fold in a number of tumors irrespective of growth rate (23). The kinetic properties of the acidic isozymes from Walker 10) and Novikoff 45) tumors indicate decreased inhibition by AMP. The Km for IMP is decreased for the Novikoff enzyme while the Km for aspartate is increased 45). These changes would favor AMP synthesis as compared to nonneoplastic cells. 

P.b. is regulated by both end products, AMP and GMP, which jointly inhibit phosphoribosylpyrophos-phate amidotransferase (EC 2.4.2.14). GMP also inhibits IMP-dehydrogenase (EC 1.2.1.14) AMP inhibits adenylsuccinate synthetase (EC 6.3.4.4). Further control is exerted by the requirement for GTP in AMP synthesis (Fig.2). ATP inhibits GMP reductase, which converts GMP into IMP in one step. 

For the sake of simplicity we shall assume that the era/site is a highly specialized promoter site, that is, the site for RNA polymerase attachment, and initiation of mRNA synthesis, the activator functional site, and that it includes the binding site for the cyclic AMP-activated CAP. AraO is the site on the DNA for repressor attachment. The efficiency of transcription of the operon is therefore dependent upon the concentration of (1) cyclic AMP (which is controlled by accumulated intermediates in L-arabinose metabolism through their effect on cyclic AMP synthesis... 

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