Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Prostaglandins E(1) and E(2) (PGE(1) and PGE(2)) stimulate adenyl cyclase activity in broken cell preparations of normal human leukocytes, whereas prostaglandin F(1a) produces no effect. PGE(1) and PGE(2) also cause increased accumulation of cyclic 3',5'-adenosine monophosphate-(3)H ((3)H-labeled AMP) in intact leukocytes which have been preincubated with adenine-(3)H in vitro. Theophylline inhibits leukocyte phosphodiesterase activity and potentiates the stimulatory effect of the prostaglandins on intracellular accumulation of cyclic 3',5'-AMP-(3)H. The ability of human granulocytes in vitro to kill Candida albicans was consistently inhibited by PGE(1) and theophylline. This effect was reproduced by dibutyryl cyclic 3',5'-AMP, a lipid-soluble analogue of the endogenous nucleotide. The inhibition of candidacidal activity could not be accounted for by drug effects on phagocytosis, oxygen consumption, or hexose monophosphate shunt activity. These results are consistent with the hypothesis that increased intracellular concentrations of cyclic 3',5'-AMP impair the granulocyte's ability to kill C. albicans, but the precise mechanism of inhibition has not yet been defined.
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PMID:Cyclic 3',5'-adenosine monophosphate in the human lukocyte: synthesis, degradation, andeffects n neutrophil candidacidal activity. 432 28

When glucose was added to a suspension of Saccharomyces cerevisiae in stationary phase, it caused a transient increase in the concentration of cyclic AMP and a more persistent increase in the concentration of hexose 6-phosphate and of fructose 2,6-bisphosphate. These effects of glucose on cyclic AMP and fructose 2,6-bisphosphate but not that on hexose 6-phosphate were greatly decreased in the presence of 0.15 mM acridine orange or when a temperature-sensitive mutant deficient in adenylate cyclase was used at the restrictive temperature. Incubation of the cells in the presence of dinitrophenol and in the absence of glucose increased the concentration of both cyclic AMP and fructose 2,6-bisphosphate, but with a minimal change in that of hexose 6-phosphate. Glucose induced also in less than 3 min a severalfold increase in the activity of 6-phosphofructo-2-kinase and this effect was counteracted by the presence of acridine orange. When a cell-free extract of yeast in the stationary phase was incubated with ATP-Mg and cyclic AMP, there was a 10-fold activation of 6-phosphofructo-2-kinase. Finally, the latter enzyme was purified 150-fold and its activity could then be increased about 10-fold upon incubation with ATP-Mg and the catalytic subunit of cyclic-AMP-dependent protein kinase. This activation resulted from a 4.3-fold increase in V and a 2-fold decrease in Km. Both forms of the enzyme were inhibited by sn-glycerol 3-phosphate. From these results it is concluded that the effect of glucose in increasing the concentration of fructose 2,6-bisphosphate in S. cerevisiae is mediated by the successive activation of adenylate cyclase and of cyclic-AMP-dependent protein kinase and by the phosphorylation of 6-phosphofructo-2-kinase by the latter enzyme. In deep contrast with what is known of the liver enzyme, yeast 6-phosphofructo-2-kinase is activated by phosphorylation instead of being inactivated.
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PMID:The mechanism by which glucose increases fructose 2,6-bisphosphate concentration in Saccharomyces cerevisiae. A cyclic-AMP-dependent activation of phosphofructokinase 2. 609 80

Recent advances in insulin secretion indicate that pertussis toxin abolishes the inhibition by alpha 2 adrenoceptor activation of insulin release by the pancreas. Pertussis toxin adenosine diphosphate (ADP) ribosylates an inhibitory guanine nucleotide-binding protein (Ni) involved in inhibition of adenylate cyclase. The decrease in cyclic adenosine monophosphate (AMP) by epinephrine may account for its inhibition of insulin release. Insulin interaction with its receptor results in an increase in the tyrosine protein kinase activity of the receptor. Second messengers for insulin are generated, hexose transport is accelerated, and a cyclic AMP-independent protein kinase is activated that phosphorylates at serinethreonine residues. The activity of membrane-bound enzymes such as adenylate cyclase and Ca2+-Mg2+-ATPase is affected. The relative importance of these effects of insulin in its regulation of cellular metabolism remains to be established.
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PMID:Insulin secretion and action. 614 90

Dopaminergic agonists which act on adenylate cyclase-linked dopamine receptor sites (D1-type) (dopamine, apomorphine and ADTN) induced a dose-dependent increase in the incorporation of L-fucose and D-mannose into glycoproteins of hippocampal, striatal and cortical slices of rat and mouse brain, whilst in rat liver slices dopamine failed to elicit such alterations in protein glycosylation. Testing in slices of rat hippocampus dopaminergic agonists with selective affinity to D2-receptors (bromocriptine, ergometrine) no changes in sugar incorporation into glycoproteins of rat hippocampus were observed. Dopamine stimulated L-fucose incorporation into rat hippocampal glycoproteins was inhibited to a different degree, but almost incompletely by dopamine receptor antagonists like haloperidol, D-butaclamol, promazine and alpha-flupenthixol, whilst chloropromazine and the selective D2-receptor antagonist sulpiride were without any effects. Also serotonin receptor antagonists (cinanserine) and beta-adrenergic receptor blockers (pindolol, alprenolol, practolol) failed to interfere with this dopamine action. But D,L-propranolol enhanced dopamine stimulated glycosylation of rat hippocampal proteins in an additive synergistic manner. This effect appeared to be not related to the antagonistic action of propranolol on beta-adrenergic receptor sites. From our results it is concluded that interactions with dopamine receptor sites (D1-type) is only one part of the mechanism triggering dopamine stimulated glycosylation of brain proteins in vitro.
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PMID:Dopamine stimulated glycosylation of brain proteins in vitro is inhibited only partially by dopamine receptor antagonists. 614 36

The human HL-60 myeloid leukaemia cell line developed, during maturational changes induced by dimethyl sulphoxide, an enhanced capacity for phorbol myristate acetate- stimulated oxidative activity and acquired a cytochrome b. Titration of the absorbance at 559 nm at potentials of-190 to -370 mV indicated that this cytochrome had a very low potential, differentiating it from mitochondrial and endoplasmic reticulum cytochromes and identifying it as the cytochrome b(-245) that has been recently found in other phagocytic cells. Subcellular fractionation studies of mature HL-60 cells showed that cytochrome b had a dual distribution within the cell. The lighter peak of activity was associated with the plasma membrane markers, adenylate cyclase and receptors for the N- formal-L-methionyl-L-leucyl-L-phenylalanine (f-Met-Leu-Phe) peptide. The denser components localized with the mitochondria but were distinct from mitochondrial cytochromes because whereas the activity of cytochrome c oxidase fell during HL-60 cell maturation, that of this cytochrome b was markedly increased. Concentrations of myeloperoxidase were unrelated to activity of the oxidase system and decreased as the cell matured. The increase in the concentrations of cytochrome b with cellular maturation parallelled the increase in the stimulated nonmitochondrial respiratory activity of these cells. The turnover of the hexose monophosphate shunt of immature cells was increased by the oxidising agents, methylene blue and tert-butylhydroperoxide, indicating that these immature cells have stimulated nonmitochondrial respiratory activity by maturing HL-60 cells is associated with, and is probably dependent upon, the acquisition by these cells of the cytochrome b(-245) oxidase system.
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PMID:Development of cytochrome b and an active oxidase system in association with maturation of a human promyelocytic (HL-60) cell line. 629 56

Under certain growth conditions, some strains of Escherichia coli accumulate toxic levels of methylglyoxal. This report characterizes a strain which synthesizes a mutant cAMP receptor protein in an adenylate cyclase deletion background. When cultured in glucose 6-phosphate minimal medium, this strain (222) was prematurely growth arrested due to methylglyoxal production; growth inhibition did not occur when the strain was grown in glucose minimal medium. A comparison of a variety of enzyme and cofactor levels in the related strains 222 (mutant) and 225 (wild-type) grown on either glucose or glucose 6-phosphate medium was carried out. The only difference found that might explain an increase in methylglyoxal accumulation was an elevated level of phosphofructokinase in strain 222 grown on glucose 6-phosphate. Since this enzyme activity probably limits hexose phosphate metabolism, it is suggested that growth inhibition in strain 222 may be due to increased production of triose phosphate, some of which is converted to methylglyoxal.
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PMID:Methylglyoxal-mediated growth inhibition in an Escherichia coli cAMP receptor protein mutant. 630 83

The effect of prostaglandin (PG) E2 on macrophage activation by interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha) was evaluated. Murine macrophages infected with Leishmania enriettii or Leishmania major were activated by exposure to IFN-gamma (10-50 U/ml) and TNF-alpha (30-3000 U/ml), leading to intracellular parasite destruction within 24-48 h. Leishmanicidal activity was markedly increased when activation was performed in the presence of PGE2 (10(-9)-10(-7) M) or arachidonate (10(-5) M, a PG precursor), concomitant with enhanced nitrite release and glucose oxidation through the hexose monophosphate shunt pathway. Conversely, activation was reduced by indomethacin and hydrocortisone, two inhibitors of PG synthesis. Parasite killing and nitrite production were fully restored by exogenous PGE2, indicating that inhibition by these drugs was related to their ability to block PG production. PG can stimulate adenylate cyclase, thus raising intracellular cAMP levels. Accordingly, dibutyryl-cAMP, theophylline (which prevents cAMP breakdown), and forskolin (an activator of adenylate cyclase) all stimulated macrophage activation. Finally, PGE2 and cAMP enhanced expression of inducible nitric oxide synthase mRNA in response to IFN-gamma and TNF-alpha, and this effect was inhibited by the cAMP antagonist 2'-O-methyl adenosine. These findings are consistent with the hypothesis that PGE2 acts as a positive agonist in macrophage activation by IFN-gamma and TNF-alpha via its capacity to modulate intracellular cAMP levels.
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PMID:Effect of PGE2 and of agents that raise cAMP levels on macrophage activation induced by IFN-gamma and TNF-alpha. 754 22

The glycolytic flux was investigated in the thermosensitive Saccharomyces cerevisiae adenylate cyclase mutant cdc35-1. Directly after a shift to restrictive temperature, the specific CO2 production rate increased from about 250 nmol min-1 (mg protein)-1 to more than 400 nmol min-1 (mg protein)-1, but then the CO2 production gradually fell to about 70 nmol min-1 (mg protein)-1 after 5 h. O2 consumption at restrictive temperature continued at more or less the same rate as at permissive temperature. The temperature shift in the mutant resulted in an increase in the estimated intracellular cAMP concentration from about 1.1 microM to 1.8 microM. This indicates that high cAMP levels are not sufficient for cell cycle progression and high glycolytic activity. The decrease in glycolytic activity at restrictive temperature was not paralleled by a similar decrease in the specific activity of any of the glycolytic enzymes, but correlated with a decrease in hexose transport. A drop in intracellular concentrations of the early metabolites of glycolysis further indicated a defect in transport at restrictive temperature. Our data suggest that glucose transport has a high control on glycolytic flux.
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PMID:Decrease in glycolytic flux in Saccharomyces cerevisiae cdc35-1 cells at restrictive temperature correlates with a decrease in glucose transport. 792 Dec 42

The transcription of the yeast FBP1 and PCK1 genes, which encode the gluconeogenic enzymes fructose-1,6-bisphosphatase and phosphoenolpyruvate carboxykinase, is repressed by glucose. Here, we show that this repression is both very strong and exceptionally sensitive to glucose, being triggered by glucose at concentrations less than 0.005% (0.27 mM). This repression remains operative in yeast mutants carrying any one of the three hexose kinases, but is lost in a triple hxk1, hxk2, glk1 mutant. In addition, 2-deoxyglucose can trigger the repression, but 6-deoxyglucose cannot, suggesting that internalization and phosphorylation of the glucose is essential for repression to occur. While gluconeogenic gene transcription is subject to the Mig 1p-dependent pathway of glucose repression, the exquisite response to glucose is maintained in hxk2 and mig1 mutants, suggesting that this pathway is not essential for the response. The response can also be triggered by the addition of exogenous cAMP, suggesting that the Ras/cAMP pathway can mediate repression of the FPB1 and PCK1 mRNAs. However, the response is not dependent upon this pathway because it remains intact in Ras, adenyl cyclase and protein kinase A mutants. The data show that yeast cells can detect very low glucose concentrations in the environment, and suggest that several distinct signalling pathways operate to repress FPB1 and PCK1 transcription in the presence of glucose.
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PMID:Multiple signalling pathways trigger the exquisite sensitivity of yeast gluconeogenic mRNAs to glucose. 879 72

Addition of glucose to yeast cells growing on less preferred carbon sources triggers profound changes in the expression levels of several genes. This paper focuses on the signal transduction pathways leading to transcriptional activation of the glycolysis in Saccharomyces cerevisiae during the transition from respiratory to fermentative growth conditions. To this end, we studied the transcriptional regulation of glycolytic genes (PFK1, PYK1 and PDC), one gluconeogenic gene (FBP1) and the two genes encoding the 6-phosphofructo-2-kinase isoenzymes (PFK26 and PFK27) during this transition. The results of experiments using glycolysis mutants, different fermentable carbon sources and 2-deoxyglucose indicate that proper transcriptional regulation of these genes is dependent on the ability to form glucose 6-phosphate by any one of the three hexose kinases. In addition, we conclude that signalling via the Ras-adenylate cyclase pathway is not necessary for the proper transcriptional response of glycolytic and gluconeogenic genes to glucose, because the transcription of these genes is not significantly affected in mutants having either high or low activities of this pathway. In contrast, the transcriptional regulation of the PFK26 and PFK27 genes is significantly altered in several of the Ras-adenylate cyclase pathway mutants studied, indicating that protein kinase A plays an important role in the transcriptional regulation of these genes.
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PMID:Signalling pathways leading to transcriptional regulation of genes involved in the activation of glycolysis in yeast. 930 11


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