Adenylate dephosphorylation

In rat heart the control rate of adenylate deaminase activity was lower, and that of adenylate dephosphorylation higher than in lung. Most of the ammonia formed from adenylate was therefore due to adenosine deaminase activity. ATP stimulated adenylate deaminase to almost the same relative degree in heart as in lung, but due to a marked inhibition of dephosphorylation the total amoimt of ammonia formed was less in heart. These data also raise questions concerning the identity and substrate specificities of the enzyme(s) that dephosphorylate adenylate and inosinate. 

Fig. 5 Proposed signal transduction mechanisms that stimulate the pheromone biosynthetic pathway in Helicoverpa zea and Bombyx mori. It is proposed that PBAN binds to a G protein-coupled receptor present in the cell membrane that upon PBAN binding will induce a receptor-activated calcium channel to open causing an influx of extracellular calcium. This calcium binds to calmodulin and in the case of B. mori will directly stimulate a phosphatase that will dephosphorylate and activate a reductase in the biosynthetic pathway. In H. zea the calcium-calmodulin will activate adenylate cyclase to produce cAMP that will then act through kinases and/or phosphatases to stimulate acetyl-CoA carboxylase in the biosynthetic pathway...

There are three important ADP receptors on the platelet surface (16). The P2X, inotrophic receptor is responsible for rapid influx of calcium into the cytosol. The P2Y, receptor mediates mobilization of calcium through activation of PLC and shape change. The P2Y,2 receptor is coupled to adenyl cyclase inhibition mediated by a G-protein with subsequent decrease in the cAMP The decrease in cAMP stimulates dephosphorylation of VASP that is closely correlated with the GPIIb/llla activation. 

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... 

The chiral y-[l80]phosphorothioate of ATP, (Pp)-ATPyS, yl80(/3, y)lsO, was synthesized by the procedure outlined in Fig. 8 [25]. (Sp)-ADPaS, alsO(a,/3)l80 was prepared by stereospecific phosphorylation of AMPaS, al802 using the adenylate and pyruvate kinase system followed by dephosphorylation with glucose and hexokinase. This was the starting material for the synthesis, with the chiral a-... 

Additionally, endothelin-1, a myocardial and endothelial peptide hormone, inhibits IKs currents presumably through inhibition of adenylate cyclase via a PTX-sensitive G protein (84), and results in APD prolongation. Because both ft-AR signaling and ETA receptor signaling result in PKA phosphorylation, the molecular mechanisms of phosphorylation and dephosphorylation of IKs are of major interest as potential therapeutic targets. 

The purine nucleotide cycle also is involved in muscle energy production. During intense stimulation, or when O2 supply is limited, the high-energy bond of ADP is used to synthesize ATP via the myokinase reaction (Figure 21-12). The resulting AMP can dephosphorylate to adenosine, which diffuses out of the cell. Conversion of AMP to IMP via adenylate deaminase and then to adenylosuccinate helps sustain the myokinase reaction, especially in FG fibers, by reducing accumulation of AMP. It may also reduce the loss of adenosine from the cell, since nucleosides permeate cell membranes while nucleotides do not. 

The answer is d. (Murray, pp 199-207. Scriver, pp 1521-1552. Sack, pp 121-138. Wilson, pp 287-317.) Epinephrine stimulates both muscle and liver adenylate cyclase to produce cyclic AMP In the liver, the increased cyclic AMP levels activate a phosphatase that dephosphorylates fructose-2,6-bisphosphate (F-2,6-BP) while deactivating a kinase that produces... 

The answer is h. (Murray, pp 123—148. Scriver, pp 2367—2424. Sack, pp 159-175. Wilson, pp 287-317.) The regulatory enzyme of lipolysis is hormone-sensitive lipase. It is a triacylglyceride lipase of adipose cells regulated by hormones. The hormones that stimulate release of fatty acids into the blood are glucagon, epinephrine, and norepinephrine, all of which activate adipocyte membrane adenylate cyclase. This produces an increased level of cyclic AMP, which activates a protein lipase that, in turn, phosphorylates and activates the sensitive lipase. In contrast, insulin causes dephosphorylation and inhibition, thereby shutting down lipolysis and the release of fatty acids into the bloodstream. 

Myosin sufficiently purified in the usual way does not dephosphorylate any of the numerous phosphate compounds of living muscle other than ATP, and perhaps ITP, nor can it transphosphorylate. Menne (1943) finds that myosin, unlike the other main fractions of muscle, can convert arginine, histidine, glycocyamine, and choline into creatine. The myosin used, however, was only reprecipitated once and subsequently washed, and it is possible that the enzyme activity might be lost on further precipitation. After fractionation and precipitating three times, myosin possesses an appreciable adenylic deaminase activity (Hermann and Josepovits, 1949 Summerson and Meister, 1944). 

As the concentration of the ligand increases, the receptor passes from the active into the desensitized state, because of the low value of constant L2, which measures the ratio RPIDP at saturation by the ligand. The receptor is now predominantly in its phosphorylated state, and its ability to activate adenylate cyclase reaches a minimum a decrease in the synthesis of cAMP ensues. Extracellular cAMP thus decreases as a result of this diminished synthesis but also because of its hydrolysis by phosphodiesterase. Owing to the drop in cAMP, the receptor progressively returns towards its active state, by dephosphorylation catalysed... 

At very low values of EC, when AMP is elevated it is deaminated via AMP deaminase to inosine monophosphate (IMP). This further displaces the adenylate kinase reaction in the direction of ATP synthesis. The IMP is dephosphorylated by nucleotide phosphatase, and the inosine is phosphorylyzed via purine nucleotide phosphorylase, releasing hypoxanthine and ribose 1-phosphate. The latter is metabolized via the pentose phosphate pathway, and most of the carbon atoms enter glycolysis. Because this course of events depletes the overall adenine nucleotide pool, and hence the scope for ATP production in the longer term, it represents a metabolic last ditch stand by the cell to extract energy even from the energy currency itself ... 

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