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 radioactive adenosine 3',5'-monophosphate (cyclic AMP) level derived from 8-14C adenine in intact rabbit platelets decreased in the presence of mitochondrial inhibitor (potassium cyanide) or uncoupler (sodium azide), and markedly increased by the addition of NaF, monoiodoacetic acid (MIA), or 2-deoxy-D-glucose. The stimulative effect of the glycolytic inhibitors was distinctly enhanced by the simultaneous addition of sodium succinate. MIA did neither directly stimulate the adenyl cyclase activity nor inhibit the phosphodiesterase activity. These results suggest that cyclic AMP synthesis in platelets is closely linked to mitochondrial oxidative phosphorylation.
Thromb Diath Haemorrh 1975 Sep 30
PMID:Dependence of platelet adenyl cyclase system on oxidative phosphorylation. 17 98

Adenosine rapidly stimulated adenylate cyclase activity but did not modify cyclic AMP degradation when added to a particulate fraction prepared from isolated bone cells. The effect of adenosine was one-half maximal at 5-10 micronM, and was not mimicked by 5' AMP, inosine, guanosine, uridine, adenine, or ribose. Basal and adenosine-stimulated adenylate cyclase activites were directly proportional to the concentration of particulate protein in the assay system. Theophylline decreased the degree to which adenosine stimulated adenylate cyclase activity, whereas another phosphodiesterase inhibitor, RO-20-1724, failed to iiinfluence the effect of adenosine. Adenosine itself, and not a metabolite of adenosine is the stimulator of adenylate cyclase, since it was neither phosphorylated nor deaminated appreciably by the particulate fraction. The particulate fraction did not convert substrate ATP to adenosine in amounts sufficient to enhance adenylate cyclase. The stimulatory effect of adenosine was maximal at 1.2 mM Mg2+, declined with increases in the Mg2+ concentration, and was replaced by inhibition at 20 mM Mg2+. At 2.4 mM Mg2+, basal adenylate cyclase activity peaked at 1.1 mM ATP, and was inhibited by higher ATP concentrations. The magnitude of adenosine stimulation was greater at inhibitory concentrations of ATP than at concentrations which yielded maximum activity. The results suggest that the previously demonstrated ability of adenosine to increase cyclic 3'5' AMP levels in intact bone cells stems from its effect on adenylate cyclase. Adenosine may act by modifying the regulatory nfluence of free Mg2+, uncomplexed ATP, (or both), on adenylate cyclase. Theophylline appears to interfere with the action of adenosine by a mechanism which is distinct from its capacity to inhibit cyclic AMP phosphodiesterase activity. (Endocrinology 99:901,1976)
Endocrinology 1976 Sep
PMID:Adenosine-mediated stimulation of bone cell adenylate cyclase activity. 18 72

Changes in cyclic-3', 5'-nucleotide phosphodiesterase activity of the peripheral blood leukocytes were investigated in patients with bronchial asthma. Leukocyte phosphodiesterase activity was significantly elevated during asthmatic attacks. Elevated activity was seen in most active asthmatics irrespective of the drug treatment. The ratio of the adenyl cyclase activity to the phosphodiesterase activity of the same leukocyte decreased to less than 1.0 during asthmatic attacks.
Ann Allergy 1976 Sep
PMID:Leukocyte cyclic-3', 5'-nucleotide phosphodiesterase activity in human bronchial asthma. 18 72

Changes in tissue levels of the low Km phosphodiesterase for adenosine 3':5'-monophosphate (cyclic AMP) and guanosine 3':5'-monophosphate (cyclc GMP) in the lung, liver, heart and brain from developing guinea pigs were studied. It was found that the contents of the soluble (cytosol) phosphodiesterase for both cyclic AMP and cyclic GMP were higher in the lung from the fetus than from the neonate and adult. The ontogenetic changes seen in the liver were qualitatively similar to thos in the lung with respect to cyclic GMP hydrolysis, while a reversed pattern of change was noted in the brain. The level of cyclic AMP phosphodiesterase was highest in the fetal heart. Throughout the fetal stage, the levels of the enzyme for cyclic GMP hydrolysis were higher than those for cyclic AMP in the lung. At or around birth, a reversal in the relative levels of the two enzymes took place; two days after birth, the level of the enzyme for cyclic AMP was 2-3times higher than thos for cyclic GMP. Kinetic analysis showed that phohphodiesterases from extracts of the lung from all developmental stages of guinea pigs had the same Km (2.6 muM) for cyclic AMP and the same Km (6.6 muM) for cyclic GMP. The relative values of V, based on assays using the same amount of enzyme protein, in decreasing order, were fetus greater than neonate greater than adult. The present findings suggest that metabolism of the two cyclic nucleotides may be closely related to developmental processes of the tissues. Moreover, the actions involving cyclic GMP may be more predominent in the fetal lung and adult brain.
Biochim Biophys Acta 1976 Sep 24
PMID:Ontogenetic changes in levels of phosphodiesterase for adenosine 3':5'-monophosphate and glucosine 3':5'-monophosphate in the lung, brain and heart from guinea pigs. 18 29

An extract of rat liver or human platelet displayed three cyclic 3':5'-nucleotide phosphodiesterase activity peaks (I, II, and III) in a continuous sucrose density gradient when assayed with millimolar adenosine 3':5'-monophosphate (cAMP) or guanosine 3':5'-monophosphate (cGMP). The three fractions obtained from each nucleotide were not superimposable. The molecular weights corresponding to the three activity peaks of cAMP phosphodiesterase in rat liver were approximately: I, 22,000; II, 75,000; and III, 140,000. In both tissues, fraction I was barely detectable when assayed with micromolar concentrations of either nucleotide, presumably because fraction I has low affinity for cAMP and cGMP. Any one of the three forms upon recentrifugation on the gradient generated the others, indicating that they were interconvertible. The multiple forms appear to represent different aggregated states of the enzyme. The ratio of the three forms of cAMP phosphodiesterase in the platelet was shifted by dibutyryl cAMP (B2cAMP) and by the enzyme concentration. B2cAMP enhanced the formation of fraction I. Low enzyme concentration favored the equilibrium towards fraction I, while high enzyme concentration favored fraction III. When phosphodiesterase activities in the extract of rat liver, human platelets, or bovine brain were examined as a function of enzyme concentration, rectilinear rates were observed with micromolar, but not with millimolar cAMP or cGMP. The specific activity with millimolar cAMP was higher with low than with high protein concentrations, suggesting that the dissociated form catalyzed the hydrolysis of cAMP faster than that of the associated form. In contrast, the specific activity with millimolar cGMP was lower with low than with high protein concentrations. Supplementing the reaction mixture with bovine serum albumin to a final constant protein concentration did not affect the activity, suggesting that the concentration of the enzyme rather than that of extraneous proteins affected the enzyme activity. A change in enzyme concentration affected the kinetic properties of phosphodiesterase. A low enzyme concentration of cAMP phosphodiesterase yielded a linear Lineweaver-Burk plot, and a Km of 1.2 X 10(-4) M (bovine), 3 X 10(-5) M (platelet), or 5 X 10(-4) M (liver), while a high enzyme concentration yielded a nonlinear plot, and apparent Km values of 1.4 X 10(-4) M and 2 X 10(-5) M (brain), 4 X 10(-5) M and 3 X 10(-6) M (platelet), or 4 X 10(-5) M and 3 X 10(-6) (liver). Since a low enzyme concentration favored fraction I, the dissociated form, whereas a high enzyme concentration favored fraction III, the associated form, these kinetic constants suggest that the dissociated form exhibits a high Km and the associated form exhibits a low Km. In contrast, a high enzyme concentration gave a linear kinetic plot for cGMP phosphodiesterase, while a low enzyme concentration gave a nonlinear plot...
J Biol Chem 1976 Sep 25
PMID:Cyclid 3':5'-nucleotide phosphodiesterase. Interconvertible multiple forms and their effects on enzyme activity and kinetics. 18 86

Depending on growth conditions, the adenosine 3':5'-cyclic monophosphate (cyclic AMP) levels of the fr mutant, a morphologically aberrant strain of Neurospora crassa, are reduced 2- to 5-fold. By taking advantage of the differences in phenotype of fr in liquid and agar cultures and the positive response of fr grown on solid support to exogenous theophylline, a relationship between the degree of morphological abnormality and intracellular cyclic AMP levels of the mutant is observed. Progressive restoration of the fr phenotype toward a normal state is paralleled by increases in cyclic nucleotide content. Striking differences in the sedimentation and thermal characteristics of the fr and wild-type adenylate cyclases [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] are observed. Approximately 50% of the normal activity sediments at 105,000 X g compared to 5% of the mutant enzyme. In addition, the overall stability of the fr adenylate cyclase is significantly decreased and its rate of inactivation at 37 degrees in the absence of substrate is 10-fold greater than the wild-type adenylate cyclase. Arrhenius plots also indicated that the Q10 (increase in rate per 10 degrees temperature increase) and the temperature of maximal activity of the fr enzyme are reduced. Supplementation of fr agar cultures with linolenic acid results in an elevated cyclic AMP content and a wild-type-like morphology similar to that obtained with inhibitors of phosphodiesterase (3':5'-cyclic AMP 5'-nucleotidohydrolase, EC 3.1.4.17). An increased thermostability of the fr adenylate cyclase occurs on linolenate enrichment of the mutant. It is concluded that the cyclic AMP deficiency is at least partially responsible for the fr phenotype and that this reduction results from a membrane defect that affects adenylate cyclase function.
Proc Natl Acad Sci U S A 1976 Sep
PMID:Adenosine 3':5'-cyclic monophosphate deficiency in Neurospora crassa. 18 53

Metabolizable sugars blocked development of the slime mold Dictyostelium discoideum; the same sugars also inhibited the formation of contact sites "A", of membranal 3':5'-cyclic adenosine monophosphate (cAMP)-binding sites, and of total cAMP phosphodoesterase (3':5'-cyclic-nucleotide phosphodiesterase; EC 3.1.4.17; 3':5'-cyclic-nucleotide 5'-nucleotidohydrolase). These inhibitory effects of the sugars on the synthesis of cellular components, required for the aggregation of developing amebae, were paralleled by an inhibition of the accumulation of cAMP which normally accompanies development. The inhibition by sugars could be overcome partially by pulsing the amebae with nanomolar concentrations of cAMP only after the amebae had acquired cAMP-binding sites. The findings suggest that metabolizable sugars inhibit development by blocking the formation of cAMP and, conversely, that development in D. discoideum may be related to the energetic state of the cell.
Proc Natl Acad Sci U S A 1976 Sep
PMID:Effect of sugars on early biochemical events in development of Dictyostelium discoideum. 18 65

Homogenates of Crithidia fasciculata (a species of Trypanosomidae) were shown to contain a phosphatase (EC 3.1.3.36) and a phosphodiesterase (EC 3.1.4.11) which hydrolyse triphosphoinositides. Approximately 30% of the diesterase and most of the phosphatase are present in the soluble fraction. The triphosphoinositide phosphatase is specifically dependent upon Mg(2+) and is stable to storage with or without freezing. The triphosphoinositide phosphodiesterase requires Ca(2+) and is inactivated during storage. Both activities are maximal in the presence of cetyltrimethylammonium bromide and require protection or reactivation by GSH or dithiothreitol. Unlike similar mammalian enzymes the protozoal triphosphoinositide phosphatase does not hydrolyse diphosphoinositides. The two enzymes may be separated by (NH4)2SO4 fractionation and gel filtration on Sephadex G-200.
Biochim Biophys Acta 1976 Sep 27
PMID:Hydrolysis of triphosphoinositides by a soluble fraction of Crithidia fasciculata. 18 23

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.
Biokhimiia 1976 Sep
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

The effect of 24 imidazol derivatives on the activity of phosphodiesterase (3', 5'-AMP-phosphohydrolase; KF3.1.4.1) was studied in the experiments with the homogenates of the rat brain and of the Rana temporaria skeletal muscles. Imidazol derivatives could produce both the activating and inhibitory influence on the enzyme. Imidazol and seven of its alkyl-substituted derivatives activated the phosphodiesterase. TTFB (tetrachloro-2-trifluoromethylbenzimidazol) produced the greatest inhibitory effect among the inhibitors on the phosphodiesterase activity.
Biull Eksp Biol Med 1976 Sep
PMID:[Effect of imidazole compounds on the activity of adenosine-3', 5'-monophosphoric acid phosphodiesterase]. 18 38


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