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:4.6.1.2 (guanylate cyclase)
8,497 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Most of the particle-bound guanylate cyclase of pigeon heart muscle, which is the predominant form of the enzyme in this tissue, co-purified with calcium pump system of the sarcoplasmic reticular fraction. Specific enzyme activity at 37 degrees C ranged up to 0.67 nmol/mg of protein/min. The K0.5 values for MnCl2, Mn2+ free, and GTP were found to be 0.72, 0.076, and 0.057 mM, respectively. Mg2+ activates and Ca2+ inhibits the enzyme in the presence of Mn2+, whereas carbamylcholine was without effect. The ratio of guanylate cyclase to adenylate cyclase activity was found to be 12:1 in the sarcoplasmic reticulum fraction and 0.5:1 in the sarcolemal fraction. Our findings suggest that the major portion of guanylate cyclase in pigeon myocardium is not directly activated by the interaction of hormones and neurotransmitters with their receptors in the cell surface membrane.
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PMID:Subcellular distribution and some properties of particulate guanylate cyclase of pigeon myocardium. 610 52

Homogeneous or partially purified soluble guanylate cyclase (GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2) from rat liver exhibited variable sensitivity to assay pH that was dependent upon buffer composition and the cation cofactor. Enzyme activity with 3 mM Mn2+ in excess of Mn2+-GTP was considerably less in Tris buffers above pH 8.0 than in glycine buffer. In the pH range of 6.0-7.6, however, manganese-supported activity was greater in Tris buffers than in imidazole or cacodylate buffers of corresponding pH. The differences in activity seen with various buffers were not apparent when Mg2+ was the sole cation cofactor but were dependent upon Mn2+ concentrations in excess of Mn2+-GTP. The effects of excess Mn2+ on guanylate cyclase varied with assay pH and buffer composition. At pH 7.6 in Tris-HCl buffer, excess Mn2+ increased guanylate cyclase activity with an apparent Ka of 0.25 mM and concentrations above 3 mM were slightly inhibitory. At pH 9.0 in Tris-HCl buffer, however, concentrations of excess Mn2+ above 0.1 mM were strongly inhibitory. By comparison, in cacodylate (pH 7.6) or glycine (pH 9.0) buffers, high concentrations of excess Mn2+ were considerably less inhibitory and the apparent Ka values for excess Mn2+ were greater than in Tris-HCl buffer at equivalent pH. The variable effects of Mn2+ on enzyme activity as a function of buffer pH and composition were qualitatively similar to its effects on catecholamine oxidation. Furthermore, the inhibition of guanylate cyclase by excess Mn2+ was partially prevented by dithiothreitol and the stimulation of enzyme activity by excess cation was completely blocked by the antioxidant hydroquinone. The studies suggest that the apparent requirement and preference of soluble guanylate cyclase for excess Mn2+ as cation cofactor, as well as the inhibition of enzyme activity by excess Mn2+ may be mediated by oxidative events associated with changes in the oxidation state of the free cation.
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PMID:Oxidative modulation of soluble guanylate cyclase by manganese. 610 32

Partial purification of soluble guanylate cyclase on DEAE-Sephacel yields two separate peaks of guanylate cyclase activity. After 10-fold purification of the soluble enzyme, guanylate cyclase is markedly inhibited by micromolar concentrations of dopamine (I50 = 0.2 microM). Dopamine inhibition is observed whether the reaction is conducted with Mn2+ or with Mg2+, under atmosphere or N2(g), and using enzyme from either peak from the DEAE-Sephacel column. Other catecholamines also inhibit partially purified guanylate cyclase with an order of potency at 1 microM of: dopamine = L-DOPA > norepinephrine = isoproterenol = adrenochrome > epinephrine. The structural requirements for inhibition are two free hydroxyl groups on the phenyl ring and an ethylamine side chain. Dopamine also inhibits the Triton X-100-solubilized microsomal guanylate cyclase after partial purification on DEAE-Sephacel. Neither chlorpromazine, propranolol, nor phentolamine at 20 microM effectively block the dopamine inhibition of partially purified soluble guanylate cyclase. Micromolar concentrations of the reducing agents dithiothreitol and glutathione also inhibit partially purified guanylate cyclase, but unlike these agents, catecholamines can inhibit whether added in the reduced or the oxidized forms. Inhibition of enzyme activity by micromolar concentrations of dopamine, adrenochrome, or dithiothreitol is rapidly reversed by dilution and the dopamine inhibition is competitive with MgGTP. Inhibition does not appear to involve covalent binding or to result from the ability of catecholamines to reduce the concentrations of oxygen or free radicals in solution.
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PMID:Catecholamine-sensitive guanylate cyclase from human caudate nucleus. 610 53

Products of the reactions catalyzed by highly purified preparations of soluble guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] from rat liver were identified and quantified with 31P NMR spectroscopy. Utilization of this technique necessitated modification of the standard assay conditions; higher concentrations of enzyme and substrate (2 mM), Mg2+ instead of Mn2+, and longer incubation times (up to 46 hr) at 30 degrees C were used. Revision of our reported procedure for purificaton of guanylate cyclase [Tsai, S-C., Manganiello, V. C. & Vaughan, M. (1978) J. Biol. Chem. 253, 8452-8457] to include chromatography on Ultrogel AcA34 and agarose-hexane-GTP provided an enzyme with specific activity higher than in our earlier preparations. 31P NMR spectra obtained during incubation of this enzyme showed that the rates of GTP disappearance and cyclic GMP (cGMP) accumulation were constant for approximately 16 hr. They indicated, however, that the preparations were contaminated with inorganic pyrophosphatase. This was removed by preparative electrophoresis, yielding enzyme with specific activities (900-1300 nmol/min per mg of protein) higher than those reported for guanylate cyclases from rat liver or lung. With this preparation, cGMP and PPi were the only products of GTP detected, consistent with the assumption that the guanylate and adenylate cyclase reactions are analogous.
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PMID:Products of reaction catalyzed by purified rat liver guanylate cyclase determined by 31p NMR spectroscopy. 610 59

Cyclic nucleotide phosphodiesterase [EC 3.1.4.17] was examined in tetrahymena pyriformis strain NT-1. Enzymic activity was associated with the soluble and the particulate fractions, whereas most of the cyclic GMP phosphodiesterase activity was localized in the soluble fraction; the activities were optimal at pH 8.0-9.0. Although very low activities were detected in the absence of divalent cations, they were significantly increased by the addition of either Mg2+ or Mn2+. A kinetic analysis of the properties of the enzymes yielded 2 apparent K(m) values ranging in concentration from 0.5 to 50 micron and from 0.1 to 62 micron for cyclic AMP and GMP, respectively. A Ca2+ -dependent activating factor for cyclic nucleotide phosphodiesterase was extracted from Tetrahymena cells, but this factor did not stimulate guanylate cyclase [EC 4.6.1.2] activity in this organism. On the other hand, tetrahymena also contained a protein activator which stimulated guanylate cyclase in the presence of Ca2+, although this activator did not stimulate the phosphodiesterase. The results suggested that Tetrahymena might contain 2 types of Ca2+ -dependent activators, one specific for phosphodiesterase and the other for guanylate cyclase.
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PMID:Studies on cyclic nucleotide metabolism in Tetrahymena pyriformis: partial characterization of cyclic AMP- and cyclic GMP-dependent phosphodiesterases. 610 21

Highly purified preparations of guanylate cyclase from rat lung were inactivated by several disulfide compounds in a time- and dose-dependent manner. Cystamine and cystine were the most potent disulfides tested, but other compounds which contained the cysteamine moiety (NH2CH2CH2S-), including pantethine and oxidized coenzyme A, were also able to partially inactivate the enzyme. In addition to the decrease in basal activity (measured with either Mg2+-GTP or Mn2+-GTP), disulfide-inhibited enzyme was activated to a lesser extent by nitric oxide. Treatment with dithiothreitol or other reducing agents restored basal activity and increased the level of cGMP production following nitric oxide activation. Control enzyme samples exhibited a single GTP Km of 25 microM or 150 microM with Mn2+ or Mg2+, respectively. However, cystamine-treated enzyme showed these same Km values as well as an additional GTP Km of 2 to 3 microM using either metal ion as cofactor. When [35S]cystine was incubated with purified enzyme, radioactivity was incorporated into the trichloroacetic acid-precipitable protein, and the counts were released following dithiothreitol treatment. In addition, [35S]cystine-labeled enzyme co-migrated with native guanylate cyclase on nondenaturing polyacrylamide gels. These data indicate that mixed disulfides can be formed between guanylate cyclase and certain naturally occurring compounds, and that disulfide formation leads to a reversible loss of enzyme activity.
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PMID:Reversible inactivation of guanylate cyclase by mixed disulfide formation. 611 Jun 65

Guanylate cyclase was purified from the soluble fraction of rat lung using a modification of procedures published previously. The purified enzyme exhibited specific activities, at pH 7.6, of 219-438 nmoles/mg protein/min and 34-60 nmoles/mg protein/min with Mn2+ and Mg2+ as cation cofactors, respectively. The specific activity changed as a function of the protein concentration due to a change in Vmax with no alteration of the Km for GTP. The enzyme migrated as a single band coincident wih guanylate cyclase activity on nondenaturing polyacrylamide and isoelectric focusing gels (isoelectric point = 5.9). Purified guanylate cyclase had an apparent molecular weight of 150,000 daltons as determined by gel filtration chromatography and polyacrylamide gel electrophoresis. Electrophoresis in the presence of sodium dodecyl sulfate revealed a single subunit of 72,000 daltons, suggesting that the enzyme is a dimer of an identical subunit. The purified enzyme could be activated by nitric oxide, indicating that this compound interacts directly with the enzyme.
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PMID:Purified guanylate cyclase: characterization, iodination and preparation of monoclonal antibodies. 611 Jun 82

Cyclic AMP formation from ATP was stimulated by unpurified and partially purified soluble hepatic guanylate cyclase in the presence of nitric oxide (NO) or compounds containing a nitroso moiety such as nitroprusside, N-methyl-N-nitro-N-nitrosoguanidine (MNNG), nitrosyl ferroheme, and S-nitrosothiols. Cyclic AMP formation was undetectable in the absence of NO or nitroso compounds and was not stimulated by fluoride or glucagon, indicating the absence of adenylate cyclase activity. The nitroso compounds failed to activate, whereas fluoride or glucagon activated, adenylate cyclase in washed rat liver membrane fractions. Cyclic GMP formation from GTP was markedly stimulated by the soluble hepatic fraction in the presence of NO or nitroso compounds. Cyclic AMP formation by partially purified guanylate cyclase was competitively inhibited by GTP and cyclic GMP formation is well-known to be competitively inhibited by ATP. Therefore, it appears that activated guanylate cyclase, rather than adenylate cyclase, was responsible for the formation of cyclic AMP from ATP. Formation of cyclic AMP of cyclic GMP was enhanced by thiols, inhibited by hemoproteins and oxidants, and required the addition of either Mg2+ or Mn2+. Further, several nitrosyl ferroheme compounds and S-nitrosothiols stimulated the formation of both cyclic AMP and cyclic GMP by the soluble hepatic fraction. These observations support the view that soluble guanylate cyclase is capable, under certain well-defined conditions, of catalyzing the conversion of ATP to cyclic AMP.
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PMID:Adenosine 3',5'-monophosphate formation by preparations of rat liver soluble guanylate cyclase activated with nitric oxide, nitrosyl ferroheme, S-nitrosothiols, and other nitroso compounds. 611 40

Effect of taurine on the properties of guanylate cyclase (GC) of the guinea-pig cardiac sarcoplasmic reticulum was studied. The enzymatic activity increased in the presence of Mn+2 at a concentration of 0.05 mM, reaching the maximal level at a concentration of 7 mM. Mg2+ (0.25-1 mM) did not alter the activity of GC in the absence of Mn2+, but stimulated it in the presence of Mn2+ at a concentration ranging within 0.1 to 1 mM. Taurine activated GC in the presence of Mn2+ (10 mM) and produced no effect on its activity at 0.5-3 mM of Mn2+ without Mg+2. Taurine (0.4-10 mM) potentiated the activity of GC stimulated with Mg+2. The structural analog of taurine, beta-alanine, suppressed the activity of GC 2-2.5-fold both in the absence and presence of Mg+2. Ca2+ (10(-9)--10(-4) mM) stimulated GC. Effect of Mg+2 and taurine on GC activity rose proportionally to an increase in Ca+2 concentration in the incubation medium. The data obtained evidence in favour of potential monitoring of the activity of GC through changes in the intracellular content of Ca+2, Mg+2 and taurine in the presence of Mn+2 at concentrations close to the physiological ones. The effect of taurine on GC is mediated via Mg+2 and Ca+2.
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PMID:[Effect of taurine on the properties of myocardial sarcoplasmic reticulum guanyl cyclase]. 611 61

A soluble, sodium-nitroprusside-stimulated guanylate cyclase as been purified from bovine lung by DEAE-cellulose chromatography, ammonium sulfate precipitation, chromatography on Blue Sepharose CL-6B and preparative gel electrophoresis. Apparent homogeneity was obtained after at least 7000-fold purification with a yield of 3%. A single stained band (Mr 72000) was observed after gel electrophoresis in the presence of sodium dodecyl sulfate. The purified enzyme migrated as one band also under non-denaturing conditions in acrylamide gels (5-12%). The mobility of this band corresponded to an Mr of 145000. The enzyme sedimented on sucrose gradients with an S20, w of 7.0 S. Gel filtration yielded a Stokes' radius of 4.6 nm. These data suggest that the enzyme has an Mr of approximately 150000 and consists of two, presumably identical, subunits of Mr 72000. Sodium nitroprusside stimulated the purified enzyme 15-fold and 140-fold to specific activities of 8.5 and 15.7 mumol of cGMP formed min-1 mg-1 in the presence of Mn2+ and Mg2+, respectively. Formation of cGMP was proportional to the incubation time and to the amount of enzyme added. The stimulatory effect of sodium nitroprusside was half-maximal at about 2 microM, was observed immediately after addition and could be reversed either by dilution or by removal of sodium nitroprusside on a Sephadex G-25 column. The purified enzyme in the absence of catalase was stimulated by sodium nitroprusside, N-methyl-N'-nitro-N-nitrosoguanidine and 3-morpholino-sydnonimine and in the presence of catalase by sodium nitrite and sodium azide. In the presence of Mn2+ and sodium nitroprusside, the purified enzyme catalyzed the formation of cAMP from ATP at a rate of 0.6 mumol min-1 mg-1.
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PMID:Purification of a soluble, sodium-nitroprusside-stimulated guanylate cyclase from bovine lung. 611 59


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