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)

The nature of the interaction of glucose with toluene-treated cells of Escherichia coli leading to inhibition of adenylate cyclase was examined by the use of analogues. Those analogues with variations of the substituents about carbon atoms 1 or 2 (e.g. alpha-methylglucoside or 2-deoxyglucose) are inhibitory, and they are also substrates of the phosphoenolpyruvate-dependent sugar phosphotransferase system. Analogues with changes in other parts of the molecule (e.g. 3-O-methylglucose or galactose), L-glucose and several disaccharides and pentoses, do not inhibit adenylate cyclase and are not substrates of the phosphotransferase system. This correlation suggests some functional relationship between the adenylate cyclase and phosphotransferase systems. Further studies were done with mutants defective in glucose enzymes II of the phosphotransferase system (designated GPT and MPT); these two activities are measured by phosphorylation of alpha-methyl-glucoside and 2-deoxyglucose, respectively. The wild-type parent phosphorylates both analogues, and both inhibit adenylate cyclase. In the GPT- mutant, alpha-methylglucoside does not inhibit adenylate cyclase and is not phosphorylated, while 2-deoxyglucose is inhibitory and phosphorylated. In the GPT- MPT- double mutant, adenylate cyclase activity is present, but neither alpha-methylglucoside nor 2-deoxyglucose inhibits adenylate cyclase, and neither sugar is phosphorylated. These studies demonstrate that glucose inhibition of adenylate cyclase in toluene-treated cells requires an interaction of this sugar with either the GPT or mpt enzyme II of the phosphotransferase system.
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PMID:Involvement of the glucose enzymes II of the sugar phosphotransferase system in the regulation of adenylate cyclase by glucose in Escherichia coli. 17 17

Toluene treatment of Escherichia coli B makes it possible to measure adenylate cyclase activity directly using [alpha-32-P]-ATP as substrate. In contrast to French press extracts, the activity of adenylate cyclase in toluene-treated cells shows many of the characteristics of the enzyme seen in the intact cell. In both toluene-treated and intact cells the activity of adenylate cyclase is inhibited at least 85% by glucose, while in French press extracts the enzyme activity is much lower and is not sensitive to inhibition by glucose. In toluene-treated cells, glucose inhibits at 10 muM, and the effect is rapid in onset and readily reversible. The activity is not inhibited by glucose 6-phosphate suggesting that glucose is responsible for the inhibition. The measurement of the activity and sensitivity to glucose of adenylate cyclase in toluene-treated cells requires the presence of potassium phosphate in the assay medium. Since it does not increase the activity or sensitivity of the enzyme in the French press extract, it is suggested that potassium phosphate is required for the maintenance of cellular integrity necessary for the activity and sensitivity of adenylate cyclase.
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PMID:Glucose-sensitive adenylate cyclase in toluene-treated cells of Escherichia coli B. 23 7

Adenylate cyclase activity was measured in suspensions of E.coli B, rendered permeable with toluene. The enzyme was activated in a dose-dependent manner by GTP and by its non-hydrolysable analogue, GTP[gamma S]. In contrast, incubation with GDP[beta S], a non-phosphorylatable analogue of GDP, caused a dose-related inhibition of adenylate cyclase; this was partially overcome by addition of GTP. GTP did not relieve, and GDP[beta S] augmented, the non-competitive and dose-related inhibition of E.coli adenylate cyclase by glucose.
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PMID:Effects of GTP,GDP[beta S] and glucose on adenylate cyclase activity of E. coli B. 388 74

In Escherichia coli, adenylate cyclase activity in toluene-treated cells can be inhibited by glucose while the activity in a broken cell preparation cannot. Adenylate cyclase activity in the permeabilized but not in broken cells is stimulated somewhat specifically and additively by potassium and phosphate. Kinetic studies show sigmoid substrate-velocity curves for the toluene-treated cells but hyperbolic curves for the broken cells. The stimulatory effects of potassium and phosphate on adenylate cyclase activity in tolulene-treated cells are associated with increases in the Vmax and Km for ATP. While the enzyme activity in toluene-treated cells shows a preference for magnesium over manganese, the reverse is observed in broken cells. Stimulation of adenylate cyclase activity in toluene-treated cells requires the presence of the proteins of the phosphoenolpyruvate:sugar phosphotransferase system (PTS). The PTS proteins can be phosphorylated in a P-enolpyruvate-dependent reaction. The stimulatory effects of ions will not occur if the PTS proteins are not phosphorylated. Since potassium phosphate stimulates both adenylate cyclase and PTS activities in toluene-treated cells, it is proposed that the effect of potassium phosphate on adenylate cyclase activity is mediated through an effect on the PTS. A model for dual regulation by glucose of adenylate cyclase activity is proposed. This model involves regulation of both the condition of the PTS proteins as well as the cellular concentration of phosphate.
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PMID:The Escherichia coli adenylate cyclase complex. Stimulation by potassium and phosphate. 388 4

The effects of toluene diisocyanate (TDI) on beta adrenergic receptor function was investigated using 2 different experimental model systems: (1) a biochemical model measured beta adrenergic adenylate cyclase activity of frog erythrocytes and (2) guinea pig tracheal smooth muscle responsiveness after in vivo exposure was used to assess physiologic function. The TDI inhibited isoproterenol-stimulated erythrocyte adenylate cyclase activity in a dose-dependent manner. Similar results were obtained with fluoride-ion-stimulated activity, suggesting that TDI caused a nonspecific inhibition of adenylate cyclase activity. No difference in tracheal smooth muscle responsiveness, measured as the concentration of isoproterenol corresponding to 50% of maximal relaxation (ED50), was observed in TDI-exposed (9.36 +/- 0.11 SE) guinea pigs when compared with control (9.38 +/- 0.06 SE) animals, nor was there a difference in the degree of maximal relaxation induced by isoproterenol. The differences between the in vitro cell studies and the tracheal smooth muscle investigations suggest that mechanisms other than direct beta adrenergic blockade should be considered in TDI-induced asthma.
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PMID:Effect of toluene diisocyanate on beta adrenergic receptor function. Biochemical and physiologic studies. 630 2

Anandamide, an endogenous eicosanoid derivative (arachidonoylethanolamide), binds to the cannabinoid receptor, a member of the G protein-coupled superfamily. It also inhibits both adenylate cyclase and N-type calcium channel opening. The enzymatic synthesis of anandamide in bovine brain tissue was examined by incubating brain membranes with [14C]ethanolamine and arachidonic acid. Following incubation and extraction into toluene, a radioactive product was identified which had the same Rf value as authentic anandamide in several thin-layer chromatographic systems. When structurally similar fatty acid substrates were compared, arachidonic acid exhibited the lowest EC50 and the highest activity for enzymatic formation of the corresponding ethanolamides. The concentration-response curve of arachidonic acid exhibited a steep slope, and at higher concentrations arachidonate inhibited enzymatic activity. When brain homogenates were separated into subcellular fractions by sucrose density gradient centrifugation, anandamide synthase activity was highest in fractions enriched in synaptic vesicles, myelin, and microsomal and synaptosomal membranes. When several areas of brain were examined, anandamide synthase activity was found to be highest in the hippocampus, followed by the thalamus, cortex, and striatum, and lowest in the cerebellum, pons, and medulla. The ability of brain tissue to enzymatically synthesize anandamide and the existence of specific receptors for this eicosanoid suggest the presence of anandamide-containing (anandaergic) neurons.
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PMID:Enzymatic synthesis of anandamide, an endogenous ligand for the cannabinoid receptor, by brain membranes. 802 36

Actinomyces viscosus T14V, a Gram-positive bacterium found in the oral cavity, was found to be insensitive to glucose-mediated catabolite repression. Basal levels of beta-galactosidase (18-26 U) were observed at all phases of growth regardless of the culture conditions. Further, beta-galactosidase could not be induced with lactose, or with a known inducer of the enzyme, isopropyl-beta-D-thiogalactoside, or with dibutyryl cAMP. Glucose, on the other hand, stimulated cAMP accumulation in a concentration-dependent manner. Fructose and sucrose mimicked the effects of glucose on cAMP accumulation, whereas galactose, mannose and maltose had lesser stimulatory effects. Other carbon sources, i.e., lactose, alpha-methylglucoside, ribose, xylose and succinate were without effect. Glucose and alpha-methylglucoside were found to stimulate cAMP accumulation in toluene-permeabilized cells, in the presence of the phosphodiesterase inhibitor, theophylline. Glucose did not stimulate cAMP levels in other Gram-positive bacteria including Streptococcus mutans, S. sanguis and S. salivarius but did cause cAMP accumulation in other strains of A. viscosus. The results suggest that glucose effects on cAMP metabolism are independent of the induction of beta-galactosidase as presently defined for Escherichia coli, and that the effects appear to be selective to the A. viscosus bacteria. The results also suggest that glucose stimulates cAMP accumulation via activation of adenylate cyclase.
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PMID:Glucose stimulates cAMP accumulation in the oral bacterium Actinomyces viscosus. 839 89

Abuse of volatile organic solvents among youth remains a major social problem. Organic solvents are cheap and relatively easy to obtain, so they carry the risk of becoming a "gateway drug" for users. The effect of repeated inhalation of toluene on subsequent responses to other drugs of abuse is unclear. In the present study, we investigated the effect of toluene inhalation on methamphetamine-induced behavioral change using a newly developed sealed inhalation shuttlebox. The influence of the cyclic AMP response element binding (CREB) protein expression following toluene inhalation was also examined. Mice were exposed to toluene or air once daily for five days. Methamphetamine produced significant hyperlocomotion in air-exposed mice. This stimulatory effect of methamphetamine was significantly enhanced following repeated inhalation of toluene. Furthermore, repeated toluene inhalation increased the levels of CREB proteins in the limbic forebrain. The present study demonstrated that adaptation of the adenylate cyclase system following repeated toluene inhalation might be involved in the expression of behavioral sensitization to subsequent methamphetamine administration. Inhalant abuse could thus be associated with the risk of other substances of abuse.
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PMID:[Neurochemical mechanisms for development of psychological dependence on volatile organic solvents]. 1841 3