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:3.1.4.1 (phosphodiesterase)
18,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activity of cyclic 3':5'-nucleotide phosphodiesterase (PDE) (EC 3.1.4.17) was measured in cultured normal and neoplastic rat mammary epithelium. Total PDE activity in normal cells was 1.6 to 6 times higher than that in tumor cells over a concentration range of 0.01 to 1 mM cyclic adenosine 3':5'-monophosphate. PDE activity was distributed between the low-speed (4000 x g) particulate and supernatant fractions in both cell lines, with the particulate fraction possessing 60 to 70% of the total. Double reciprocal kinetic plots were nonlinear, suggesting the presence of high- and low-affinity PDE activities. Similar, but not identical biphasic curves obtained from both normal and neoplastic cells suggested that at least two different PDE activities were present in a membrane-bound as well as a soluble form. Apparent Michealis constants for the high-affinity enzyme ranged from 2 to 6 muM; the low-affinity enzyme was 1 mM. In the presence of 10 mM caffeine and at a substrate concentration of 1 muM, PDE activity was inhibited 40 and 80% of basal levels in normal and tumor cells, respectively. In general, the membrane-bound enzyme was inhibited to a greater extent than the soluble, regardless of the cell line examined. Although normal cells exhibited higher PDE activities in terms of total specific activity, when soluble activities were compared at low substrate concentrations, the opposite was the case. At a substrate concentration of 0.01 muM, normal cell, low-Km soluble specific activity was 40% less than comparable tumor cell activity. Our results support the contention that PDE is induced by its own substrate, cyclic adenosine 3':5'-monophosphate. In addition, they suggest that the low cyclic adenosine 3':5'-monophosphate steady-state levels characteristic of malignant cells are maintained by a soluble high-affinity isozyme of PDE.
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PMID:Cyclic nucleotide phosphodiesterase activity in normal and neoplastic rat mammary cells grown in monolayer culture. 17 39

Insulin accelerates the entry of glucose and amino acids into muscle cells by acting upon the 'carrier-facilitated' transport mechanism. For glucose this process is passive and leads to equilibration of intracellular and extracellular concentrations. In heart muscle, glucose transport is a rate-limiting step for glucose uptake. During hypoxia and ischemia the heart turns to anaerobic glycolysis for energy production and therefore, maximal glucose transport becomes important. Insulin is necessary to insure proper protein synthesis, probably at the level of membrane-bound polyribosomes. However, during myocardial hypoxia, insulin alone cannot restore the associated depression in protein synthesis. Although insulin hyperpolarizes the cell, a change in the ratio of intracellular to extracellular activities of potassium is not its primary mode of action. An insulin-induced configurational change in the plasma membrane could simultaneously account for the effects of insulin on sodium and potassium permeability and the action on facilitated transport. Intracellular levels of cyclic adenylate may be reduced by insulin in adipose tissue because of inhibition of adenyl cyclase or stimulation of phosphodiesterase. However, at this time there is little evidence that insulin alters cyclic AMP levels in the heart. Insulin secretion is depressed in patients with heart disease in proportion to the reduction of cardiac index sustained. Since the ischemic heart is dependent upon glucose as the major fuel, insulin lack may deprive the heart of adequate substrate.
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PMID:Insulin: fundamental mechanism of action and the heart. 18 67

Sucrose, a widely used agent in the preparation of membranes, inhibited the alkaline phosphomonoesterase of the milk fat globule membrane in both its membrane-bound and detergent-solubilized forms. The inhibition was kinetically competitive and reversible by dialysis. However, its mechanism was more complex than simple competition with substrate because: (a) sucrose induced the appearance of prolonged time-lags in the progress curves of the enzyme; (b) the extent of inhibition and of the time-lags depended on the age of the membrane preparation, the period of pre-exposure of the membranes to sucrose, and the temperature of pre-exposure. On the other hand the acid phosphomonoesterase and the phosphodiesterase activities also present in the membrane preparations were unaffected by the disaccharide.
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PMID:Milk fat globule membranes. Inhibition by sucrose of the alkaline phosphomonoesterase. 18 35

Fragments of sarcoplasmic reticulum from rabbit sceletal muscles sedimented within the range from 2000 g to 8000 g (heavy fraction) and 8000 g to 40000 g (light fraction) and washed with 0.6 M KCl, were practically free of adenylatecyclase activity. Phosphodiesterase cAMP was not found in the light fraction, while its activity in the heavy fraction was 500 pmol of cAMP/min per mg of protein. Both fractions contain bound cAMP (1-2 pmol/mg of protein) and specific sites of cAMP binding, the binding constant being approximately 10(6)M-1. The number of binding sites is 60 pmol/mg of protein for the heavy and 30 pmol/mg of protein for the light fractions. The level of phosphodiesterase activity in the heavy fraction correlates with its sensitivity to imidazole, anserine and caffeine. Imidazole and anserine increase in 1.5-1.8 times the value of Ca2+/ATP in the heavy fraction and produce no effect on Ca2+ transport by the light fraction. Caffeine decreases almost twice the Ca2+/ATP value in the heavy fraction and has practically no effect on Ca2+ absorption by enzymes of the light reticulum fraction. Imidazole and anserine activate membrane-bound phosphodiesterase, while caffeine inhibits it. It is suggested that structural rearrangements of membrane-bound phosphodiesterase under the effect of caffeine, imidazole and anserine are responsible for changes in the efficiency of Ca2+ transport by fragments of the heavy reticulum fractions.
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PMID:[Concentration of components of the adenylate system in heavy and light fractions of the sarcoplasmic reticulum of skeletal muscles and sensitivity of these fractions to the effects of imidazole-containing compounds and caffeine]. 18 55

Adenosine 3',5'-cyclic monophosphate phosphodiesterase (EC 3.1.4.17) has been investigated in rat liver as to its insulin sensitivity. Hormone action has been assayed in vitro on a liver homogenate purified by DEAE-cellulose column chromatography, on isolated hepatocytes, on isolated plasma membranes. The DEAE-cellulose chromatography purified homogenate showed no sensitivity to insulin, whereas isolated hepatocytes incubated in presence of insulin showed increased phosphodiesterase activity in a plasma membrane-containing fraction. The plasma membrane-bound enzyme, which shows both high and low affinity components, was significantly stimulated after hormonal treatment; this effect being dependent on a V increase of the low Km form.
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PMID:Insulin-sensitive adenosine 3',5'-cyclic monophosphate phosphodiesterase of hepatocyte plasma membrane. 18 34

Chlorpropamide and phenformin inhibited (Na+ - K+)-ATPase and stimulated a high affinity cyclic AMP-phosphodiesterase of isolated liver plasma membrane when tested in vitro. In addition, the two drugs decreased the intracellular cyclic AMP content of isolated hepatocytes without being effective on plasma membrane-bound adenylate cyclase. The results suggest that the plasma membrane plays an important role in the mechanism of action of the two hypoglycemic drugs, but do not exclude the presence of intracellular targets.
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PMID:Effect of chlorpropamide and phenformin on rat liver: the effect on plasma membrane-bound enzymes and cyclic AMP content of hepatocytes in vitro. 20 70

The activity of cyclic AMP phosphodiesterase (3':5'-cyclic-nucleotide 5'-nucleotidohydrolase, EC 3.1.4.17) in 105 000 X g supernatant fraction from frozen-thawed rat liver was 2.5 times higher than the corresponding preparation from fresh liver. This increased activity of frozen liver enzyme was accompanied by a decreased sensitivity of the enzyme to known activators such as alpha-tocopheryl phosphate and trypsin. Neither membrane-bound cyclic AMP phosphodiesterase, nor supernatant cyclic GMP phosphodiesterase increased in frozen liver preparation. It is unlikely that the activator protein of phosphodiesterase participated in the observed change of enzyme activity. Among rat tissues so far tested, the increased level of cyclic AMP phosphodiesterase was noted only in tissues rich in lysosome content. In the recombination experiment where phosphodiesterase from fresh liver was incubated with lysosomal fraction, stimulation of the enzyme activity was observed with a concomitant loss of sensitivity to above-mentioned activators. Since the stimulation by lysosomal fraction was effectively inhibited by cathepsin B1 inhibitors, leupeptin and antipain, it was deduced cathepsin-B1 (EC 3.4.12.3) type protease(s) was the main causative of activating the cyclic AMP phosphodiesterase. The freezing-thawing process of rat liver made the lysosomal membrane more permeable, and hence lysosomal proteases were released into soluble fraction during phosphodiesterase preparation. These results provide a warning not to use frozen liver for phosphodiesterase preparation, otherwise altered properties of the enzymes will be seen.
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PMID:Increased activity of cyclic AMP phosphodiesterase from frozen-thawed rat liver. A role of lysosomal protease in enzyme activation. 20 22

We have found evidence that transcription of the galactokinase (ATP:D-galactose 1-phosphotransferase; EC 2.7.1.6) gene is inhibited, in the animal-like protozoan Tetrahymena, by dibutyryl adenosine 3':5'-cyclic monophosphate, glucose, and epinephrine. The specific activities of galactokinase in Tetrahymena cells grown in defined media with galactose or glycerol as the principal carbon source are equivalent; the specific activity in glucose minimal medium is [unk] the value. Thus, while there seems to be no specific induction of the enzyme by the substrate, galactose, there is a strong "repression" by glucose. This repression by glucose is mimicked, in glycerol-grown cells, by the addition of millimolar amounts of dibutyryl adenosine 3':5'-cyclic monophosphate or phosphodiesterase inhibitors such as caffeine and theophylline. When glucose-grown cells are washed and resuspended in carbohydrate-free medium, the galactokinase specific activity increases by as much as 10-fold within 12 hr. This increase is blocked by dibutyryl adenosine 3':5'-cyclic monophosphate and by epinephrine (synthesized by Tetrahymena, and previously shown to activate a membrane-bound adenylate cyclase in extracts of this organism), as well as by inhibitors of mRNA synthesis, maturation, and translation. Our results suggest that glucose and epinephrine can regulate transcription of the galactokinase gene by modulation of cyclic nucleotide levels. The observation that the nonmetabolized sugars 2-deoxyglucose, 2-deoxygalactose, and alpha-methylglucoside are as effective as glucose suggests that the sugar itself, or an immediate metabolite such as the 1-phosphate derivative, may be the effector.
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PMID:Genetic regulation of galactokinase in Tetrahymena by cyclic AMP glucose, and epinephrine. 20 71

Activity, ratio and summary content of cyclic AMP enzymes, adenylate cyclase and phosphodiesterase varied depending on growth conditions of phototrophic bacteria (Rhodospirillum rubrum and Rhodopseudomonas palustris). It suggests, that membrane-bound and soluble enzymes carry different functions. The increase of adenylate cyclase under chaning growth conditions was usually accompanied by the increase of phosphodiesterase. Sharp increase of both enzymes activity was observed when bacteria were growth in aerobic conditions. The activity of both enzymes in chromatophores was 2.8-fold higher when bacteria were grown in the light in anaerobic conditions, than in chromatophores of bacteria grown under stationary aerobic conditions in the light. It is suggested that 3':5' AMP can participate in autotrophic carbon assimilation or in the synthesis of pigments and other components of bacterial photosynthetizing apparatus. Substitution of NH4+ into NO3- and glutamate under the growing of R. rubrum in anaerobic conditions in the light resulted in the increase of the enzymes activities, which is the evidence of possible role of 3':5' AMP in mineral nitrogen uptake and nitrogen fixation. Glutamate concentration of 4 g/l stimulated the enzymes both in vivo and in vitro. The data obtained suggest that 3':5' AMP can carry multiple functions, participating in regulation of a number of metabolic processes in photorophic bacteria.
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PMID:[Effect of growth conditions on the activity of the enzymes of cyclic 3':5'-AMP synthesis and decay in phototrophic bacteria]. 20 63

In the cellular slime mould Dictyostelium, a membrane-bound cyclic AMP phosphodiesterase undergoes a tenfold increase in activity when amoebae reach the aggregation stage of development. Our previous studies had shown that when non-aggregating cells, which produce extracellular and intracellular forms of the enzyme, are treated with the lectin Concanavalin A (Con A), they exhibit prematurely high levels of the membrane bound enzyme. The present results indicate that this effect may be largely due not to the induction of the enzyme by Con A but rather to the binding of the intracellular form of the enzyme to membranes by Con A. This conclusion is based on the findings that: a) the enzyme activity associated with membranes from Con A treated cells can be decreased by treatment with the haptenic sugar alpha-methyl mannoside: b) mambranes from untreated cells having only low membrane-bound phosphodiesterase activity can acquire increased activity after incubation with Con A and intracellular phosphodiesterase; c) the intracellular phosphodiesterase binds to Sepharose-Con A and is eluted with alpha-methyl mannoside. These results raise the possibility that some of the effects attributed to Con A in the literature may not be due directly to Con A but to glycoproteins attached to membranes by Con A.
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PMID:Concanavalin-mediated attachment to membranes of a cellular slime mould cyclic AMP phosphodiesterase. 20 15


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