Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

(1) A system is described for studying the short-term effects of agents on proinsulin synthesis in vitro, as measured by the incorporation of [3H]leucine into isolated proinsulin. (2) Of the agents tested, glucose has the most marked, and apparently earliest, effect on proinsulin synthesis. (3) The adenyl cyclase system participates in the regulation of proinsulin synthesis since exogenous cyclic AMP, glucagon, and caffeine are stimulatory. When cyclic AMP is added to the medium in the presence of glucose, it is the most potent agent acting on the adenyl cyclase-phosphodiesterase system. (4) The addition of NADPH to isolated rat islets inhibits proinsulin and Bulk Protein synthesis in vitro.
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PMID:Regulation of proinsulin synthesis in isolated rat islets. 0 29

Sarcoplasmic reticulum fragments isolated from dog cardiac muscle possess a calcium-accumulating system associated with a series of enzymes linked to glycogenolysis. These enzymes include: adenylate cyclase, cyclic AMP-dependent protein kinase, phosphorylase b kinase, phosphorylase (b/a, 30/1),"debrancher" enzyme, and glycogen (0.3 to 0.7 mg/mg of protein). The sarcoplasmic reticulum preparation produced glucose 1-phosphate and glucose from either endogenous or exogenous glycogen. Both the calcium-accumulating and glycogenolytic enzymes sediment in a single peak at 33% sucrose on a linear continous sucrose density gradient, and the complex remains intact throughout repeated washing. Glycogen particles appear to be associated with the sarcoplasmic reticulum in situ as well as in the isolated microsomal fraction. The sarcoplasmic reticulum-glycogenolytic complex, monitored by a linked enzyme spectrophotometric assay, shows several features: (a) activation of phosphorylase activity to peak rate occurs over a very rapid time course which cannot be duplicated using combinations of purified enzymes; (b) activation is inhibited by protein kinase inhibitor; (c) phosphorylase b functions as in the purified form with respect to AMP (Km, 0.3 mM); (d) in the presence of limiting amounts of glycogen, optimal phosphorylase b activity in the sarcoplasmic reticulum requires the presence of debrancher, and the activity is sensitive to inhibitors of that enzyme such as Tris, which suggests the possiblity that the enzymes bear a specific structual relationship to the glycogen present. Phosphorylase b leads to a activation in the sarcoplasmic reticulum was completely resistant to ethylene glycol bis(beta-aminoethyl either)-N,N'-tetraacetic acid (EGTA). Inhibition of calcium accumulation by or release of bound calcium from sarcoplasmic reticulum by X537A (RO 2-2985) did not alter the EGTA resistance. These results suggest that cardiac sarcoplasmic reticulum is a complex organelle containing functions that may be related to excitation-contraction coupling and intermediary metabolism.
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PMID:Association of gylcogenolysis with cardiac sarcoplasmic reticulum. 0 55

The behavior of a model for the partial depletion of adenine nucleotides in the perfused rat heart has been compared for ischemic and high coronary flow anoxic conditions. The accumulation of noradrenaline in the interstitial fluid greatly activates adenylate cyclase ultimately resulting in the degradation of 11.02 micronmol/g dry wt of ATP to adenosine, inosine, and hypoxanthine in 30 min. The high coronary flow rate during anoxic perfusion promotes washout of the noradrenaline from the interstitial fluid so that the hormone accumulates to only one fifth of its highest level in ischemia. This results in only slight activation of adenylate cyclase and in insignificant degradation of ATP in 2 min. The behavior of the model has been examined for two aerobic conditions--a transition from light to heavy work (2 min) and a transition from substrate-free to glucose perfusion (12 min), In both cases adenylate cyclase was not activated above its basal activity, and insignificant depletion of adenine nucleotides is predicted by the model.
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PMID:Computer simulation of ischemic rat heart purine metabolism. II. Model behavior. 1 61

Sugars such as glucose are transported into Escherichia coli by a coupled phosphorylation mechanism (the phosphoenolpyruvate:sugar phosphotransferase system, PTS). Transport of sugars through the PTS results in inhibition of adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] activity by a mechanism involving a change in the state of phosphorylation of PTS proteins. Other sugars (e.g., lactose) are transported without modification by a mechanism involving proton cotransport, which requires a proton motive force across the cell membrane. We show here that uptake of sugars through the lactose transport system results in inhibition of adenylate cyclase activity if the proton symport mechanism is also active. The protonophore carbonyl cyanide m-chlorophenylhydrazone also inhibits adenylate cyclase activity. These data suggest that the steady-state electrochemical proton gradient regulates the activity of adenylate cyclase. We propose that sugar-dependent inhibition of adenylate cyclase activity may occur by either of two mechanisms. Sugars transported by the PTS inhibited adenylate cyclase activity by dephosphorylation of a regulatory protein, while sugars transported by the proton motive force system inhibit adenylate cyclase activity as a result of collapse of the proton electrochemical gradient.
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PMID:Escherichia coli adenylate cyclase complex: regulation by the proton electrochemical gradient. 10 76

Red blood cell plasma membranes contain a number of enzymes: ATPases, anion transport protein, glyceraldehyde 3-phosphate dehydrogenase, protein kinases, adenylate cyclase, acetylcholinesterase. Most of them are tightly bound to the membrane and are present in small amounts. As a result, structural characterization of erythrocyte membrane enzymes has not yet been successful. Functional studies have, however, yielded a great deal of information. ATPases allow active transport of cations (calcium, sodium, potassium). Anion transport protein controls movements of chloride and phosphate ions, and of glucose and water. Among glycolytic enzymes: glyceraldehyde 3-phosphate dehydrogenase is partially bound to the membrane. Protein kinases catalyze the phosphorylation of several membrane proteins, one of which (spectrin) is involved in red blood cell mechanical properties. The physiological role of adenylate cyclase is unknown. Acetylcholinesterase is an ectoenzyme. Calcium-dependent ATPase, adenylate cyclase and phosphorylation of erythrocyte membrane proteins have been found abnormal in various conditions: hereditary spherocytosis, sickle-cell anemia, progressive muscular dystrophies, all of these disorders being associated with a decreased deformability of the erythrocyte.
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PMID:The enzymes of the red blood cell plasma membrane. 14 25

The present study was undertaken to investigate the mechanism of the antilipolytic action of clofibrate (p-chlorophenoxyisobutyrate). Clofibrate, in the dose range of 10-80 mg/199 ml, inhibited the initial rate of norepinephrine-stimulated lipolysis 17-44 percent in isolated rat fat cells. At a dose corresponding to therapeutic levels in vivo (10 mg/100 ml) clofibrate also inhibited hormone-stimulated lipolysis by 20-30 percent in fragments of human subcutaneous fat. Inhibition of lipolysis by clofibrate occurred at all concentrations of norepinephrine and ACTH (0.02-0.1 mug/ml) but did not occur with equilipolytic concentrations of dibutyryl cyclic AMP, suggesting a proximal site of action on the lipolytic sequence. Clofibrate reduced by 60 percent (315plus or minus40 vs. 120plus or minus25 pmol/g lipid; meanplus or minusSEM) the norepinephrine-stimulated initial rise in cyclic AMP, measured 10 min after addition of hormone. Because the antilipolytic effect occurred in the presence of glucose and without altering cellular ATP levels, the reduction in intracellular cyclic AMP levels could not be attributed to uncoupling of oxidative metabolism or to secondary effects of free fatty acid accumulation. In the secondary effects of free fatty acid accumulation. In the presence of procaine-HC1, which blocks hormone-stimulated lipolysis without inhibiting cyclic AMP accumulation, addition of clofibrate prevented the hormone-stimulated rise in cyclic AMP. Clofibrate did not affect the activity of the low-Km 3',5'-cyclic AMP phosphodiesterase in norepinephrine-stimulated adipocytes. These data suggest that the antilipolytic effect of clofibrate is due to its suppression of cyclic AMP production by inhibition of adenylate cyclase. The drug's hypolipidemic action may in part be explained by its antilipolytic effect, which deprives the liver of free fatty acid substrate for lipoprotein synthesis.
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PMID:Inhibition of hormone-stimulated lipolysis by clofibrate. A possible mechanism for its hypolipidemic action. 16 83

The extracellular concentration of cyclic adenosine 3',5'-monophosphate (AMP) of three different strains of Vibrio cholerae growing in syncase medium were measured. Cyclic AMP secreted by V. cholerae 569B varied widely, with different carbon sources. Mutant 13, which produced little or no toxin, released half the amount of cyclic AMP as the wild type. The release of less cyclic AMP into the medium by mutant 13 may be accounted for by the lower activity of adenylate cyclase observed. High glucose (3%) in the culture medium reduced the concentration of cyclic AMP both in wild type and mutant 13. Reduction of cyclic AMP levels at high concentrations of glucose (3%) occurred without change of adenylate cyclase activity. The release of enterotoxin to the medium varied with carbon sources but was independent of conditions which reduced the cyclic AMP both within the cell and the medium. Neither adenylate cyclase activity nor toxin production was reduced by an increase concentration of glucose in wild-type V. cholerae, whereas cyclic AMP levels were reduced by sixfold. A lower activity of the adenylate cyclase was observed in a mutant of V. cholerae which produced no detectable toxin. Thus, a correlation exists between toxin production and adenylate cyclase activity in V. cholerae.
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PMID:Adenosine 3',5'-cyclic monophosphate in Vibrio cholerae. 16 19

In fat cells isolated from the parametrial adipose tissue of rats, the addition of purified adenosine deaminase increased lipolysis and cyclic adenosine 3':5'-monophosphate (cyclic AMP) accumulation. Adenosine deaminase markedly potentiated cyclic AMP accumulation due to norepinephrine. The increase in cyclic AMP due to adenosine deaminase was as rapid as that of theophylline with near maximal effects seen after only a 20-sec incubation. The increases in cyclic AMP due to crystalline adenosine deaminase from intestinal mucosa were seen at concentrations as low as 0.05 mug per ml. Further purification of the crystalline enzyme preparation by Sephadex G-100 chromatography increased both adenosine deaminase activity and cyclic AMP accumulation by fat cells. The effects of adenosine deaminase on fat cell metabolism were reversed by the addition of low concentrations of N6-(phenylisopropyl)adenosine, an analog of adenosine which is not deaminated. The effects of adenosine deaminase on cyclic AMP accumulation were blocked by coformycin which is a potent inhibitor of the enzyme. These findings suggest that deamination of adenosine is responsible for the observed effects of adenosine deaminase preparations. Protein kinase activity of fat cell homogenates was unaffected by adenosine or N6-(phenylisopropyl)adenosine. Norepinephrine-activated adenylate cyclase activity of fat cell ghosts was not inhibited by N6-(phenylisopropyl)adenosine. Adenosine deaminase did not alter basal or norepinephrine-activated adenylate cyclase activity. Cyclic AMP phosphodiesterase activity of fat cell ghosts was also unaffected by adenosine deaminase. Basal and insulin-stimulated glucose oxidation were little affected by adenosine deaminase. However, the addition of adenosine deaminase to fat cells incubated with 1.5 muM norepinephrine abolished the antilipolytic action of insulin and markedly reduced the increase in glucose oxidation due to insulin. These effects were reversed by N6-(phenylisopropyl)adenosine. Phenylisopropyl adenosine did not affect insulin action during a 1-hour incubation. If fat cells were incubated for 2 hours with phenylisopropyl adenosine prior to the addition of insulin for 1 hour there was a marked potentiation of insulin action. The potentiation of insulin action by prior incubation with phenylisopropyl adenosine was not unique as prostaglandin E1, and nicotinic acid had similar effects.
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PMID:Effects of adenosine deaminase on cyclic adenosine monophosphate accumulation, lipolysis, and glucose metabolism of fat cells. 16 37

1. The effect of carbon source variation in bacterial growth media on their growth rate, inducible enzyme and cyclic AMP synthesis was examined: an inverse relationship between the culture's growth rate and its differential rate of inducible enzyme (tryptophanase and beta-galactosidase), and cyclic AMP synthesis was found. 2. The effect of the culture's growth phase on its sensitivity or resistance to glucose catabolite repression was determined in the wild type and a catabolite insensitive mutant (ABDROI): the wild type's sensitivity to glucose repression was not affected, whereas the insensitivity of the mutant was found to be limited to its early logarithmic phase of growth. At late log, or stationary phase, the mutant was found to be sensitive to glucose repression. 3. Examination of the kinetics of glucose uptake by the mutant, using alpha-[1 4-C] methyl-glucoside showed evidence for two transport systems each with a different affinity to glucose. A low affinity transport system (apparent Km of 3.4-10-minus 5 M) which appears mostly at the early logarithmic phase of growth. A high affinity transport system (apparent Km of 1.2-10-minus 5 M) which appears mostly at the late log and stationary phases of growth. 4. The effect of the culture density variation on its sensitivity to glucose repression showed that sensitivity to glucose catabolic repression is primarily a reflection of the formation of an allosteric effector molecule between glucose and its specific transport molecule which in turn regulates the activity of the adenylate cyclase.
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PMID:On the regulation of adenosine 3', 5'-monophosphate synthesis in bacteria. I. Effect of carbon source variation on cyclic AMP synthesis in Escherichia coli B/r. 16 29

1. The in vitro regulation of the membrane bound adenylate cyclase of Escherichia coli B/r by a variety of carbohydrates and one mammalian hormone was examined. 2. The membrane bound adenylate cyclase was found responsive to regulation by the various growth substrates and to glucagon. 3. Solubilization of the bacterial membrane preparation by a procedure specific for the solubilization of the phosphotransferase enzyme E1 1 to its E1 1 A and E1 1 B subunits was found to be accompanied by the loss of the adenylate cyclase regulation by glucose. 4. Reconstitution of the membrane was found to result in a recovery of the regulative response of the adenylate cyclase to glucose. 5. A model for the intermediate steps in the interaction between glucose and phosphotransferase E1 1 and the adenylate cyclase is discussed.
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PMID:On the regulation of cyclic AMP level in bacteria. II. In vitro regulation of adenylate cyclase activity. Solubilization and reconstitution of a functional membrane-bound adenylate cyclase system responsive to regulation by glucose. 16 30


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