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)

Cytochemical and biochemical characteristics of the surface membrane components of avian dystrophic muscle were examined. A Mg2+- or Ca2+-activated ("basic") adenosine triphosphate (ATPase) was localized cytochemically in fixed, intact dystrophic muscle slices in a medium containing Mg2+ or Ca2+, adenosine triphosphate (ATP), and 1 microM free Pb2+ to capture enzymatically released phosphate ions. Electron-dense staining precipitates were found to be associated with the plasmalemma and its tortuous invaginations, and the transverse components of the T-system membrane and its associated proliferated networks. Enzymatic analysis of microsomal fractions isolated from 7-day-old and 90-day-old normal and dystrophic muscle showed a complex behavior. Specific activity of "basic" ATPase decreased with maturity in normal and dystrophic animals. The specific activities of the surface membrane associated enzymes, leucyl beta-naphthylamidase, adenylate cyclase, and guanylate cyclase, remained at various elevated levels in the mature dystrophic animals, in contrast to the normal muscle, which showed decreases in the specific activity of all three enzymes with maturation. The persistent high levels in some but not all enzyme activities in 90-day-old dystrophic muscle indicates a complicated developmental pattern in the dystrophic chicken muscle.
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PMID:Biochemical and cytochemical comparison of surface membranes from normal and dystrophic chickens. 611 29

In our studies with purified soluble guanylate cyclase from rat lung, we have tested a number of guanosine 5'-triphosphate (GTP) analogues as substrates and inhibitors, 5'-Guanylylimidodiphosphate (GMP-P(NH)P), guanylyl (beta, gamma-methylene) diphosphate (GMP-P(CH2)P), and guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) were found to be substrates for guanylate cyclase. GTP gamma S supported cyclic GMP formation at 20 or 75% of the rate seen with Mn2+-GTP and Mg2+-GTP, respectively. GMP-P(NH)P and GMP P(CH2)P supported cyclic GMP formation at 10-20% of the GTP rate with either cation cofactor. These analogues were found to have multiple Km values; one Km value was similar to GTP (150 microM with Mg2+, 20-70 microM with Mn2+), but an additional high affinity catalytic site (3 microM) was also observed. Guanosine tetraphosphate (Ki = 10 microM), adenosine triphosphate (Ki = 9 microM) and the 2'3'-dialdehyde derivative of GTP (dial GTP) (Ki = 1 microM) were not good substrates for the enzyme; however, they were potent competitive inhibitors. These GTP analogues will be useful tools for the study of GTP binding sites on guanylate cyclase and they may also help elucidate the effects of free radicals and other agents on guanylate cyclase regulation.
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PMID:Effect of GTP analogues on purified soluble guanylate cyclase. 612 Jan 66

The stability of dopamine-sensitive adenylate cyclase, guanylate cyclase, ATPase, and GTPase was measured in homogenates of rat striatal tissue frozen from 0 to 24 h postmortem. ATPase, GTPase, and Mg2+-dependent guanylate cyclase activities showed no significant change over this period. Mn2+-dependent guanylate cyclase activity was stable for 10 h postmortem. Basal and dopamine-stimulated adenylate cyclase activity decreased markedly during the first 5 h. However, when measured in washed membrane preparations, these adenylate cyclase activities remained stable for at least 10 h. Therefore, the postmortem loss of a soluble activator, such as GTP, may decrease the adenylate cyclase activity in homogenates. These results are not consistent with an earlier suggestion that there is a postmortem degradation of the enzyme itself. Other kinetic parameters of dopamine-sensitive adenylate cyclase can also be measured independently of postmortem changes. Thus, it is possible to investigate kinetic parameters of dopamine-sensitive adenylate cyclase, guanylate cyclase, ATPase, and GTPase in human brain obtained postmortem.
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PMID:Postmortem stability of dopamine-sensitive adenylate cyclase, guanylate cyclase, ATPase, and GTPase in rat striatum. 612 Sep 96

Highly purified rat lung soluble guanylate cyclase was activated with nitric oxide or sodium nitroprusside and the degree of activation varied with incubation conditions. With Mg2+ as the action cofactor, about 2- to 8-fold activation was observed with nitric oxide or sodium nitroprusside alone. Markedly enhanced activation (20-40 fold) was observed when 1 muM hemin added to the enzyme prior to exposure to the activating agent. The activation with hemin and sodium nitroprusside was prevented in a dose-dependent manner by sodium cyanide. The level activation was also increased by the addition of 1 mM dithiothreitol, but unlike hemin which had no effect on basal enzyme activity, dithiothreitol led to a considerable increase in basal activity. Activated guanylate cyclase decayed to basal activity within one hour at 2 degrees C and the enzyme could be reactivated upon re-exposure to nitroprusside or nitric oxide. Under basal conditions, Michaelis-Menten kinetics were observed, with a Km for GTP of 140 muM with Mg2+ cofactor. Following activation with nitroprusside or nitric oxide, curvilinear Eadie-Hofstee transformations of kinetic data were observed, with Km's of 22 MuM and 100 MuM for Mg-GTP. When optimal activation (15-40 fold) was induced by the addition of hemin and nitroprusside, multiple Km's were also seen with Mg-GTP and the high affinity form was predominant (22 MuM). Similar curvilinear Eadie-Hofstee transformations were observed with Mn2+ as the cation cofactor. These data suggest that multiple GTP catalytic sites are present in activated guanylate cyclase, or alternatively, multiple populations of enzyme exist.
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PMID:Properties of purified soluble guanylate cyclase activated by nitric oxide and sodium nitroprusside. 612 56

Rat fat cell plasma membrane preparations were used to study the effect of Mn2+, Mg2+, Ca2+ on guanylate cyclase activity. Among these three cations, Mn2+ was the most effective in activating the enzyme; Mg2+ and Ca2+ were 23% and 10% respectively as effective as Mn2+ in activating the enzyme. Low concentrations of Ca2+ (1 microM) increased the rate of cGMP formation at MgGTP concentrations ranging from 0.3 to 2 mM. This effect was less at higher concentrations of Ca2+ and was independent of the presence of excess Mg2+. Ca2+ (100 microM) had only a marginal stimulatory effect on the MnGTP-dependent enzyme.
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PMID:Membrane bound guanylate cyclase in rat fat cell plasma membranes: influence of divalent cations on calcium activation. 612 84

Bovine lung soluble guanylate cyclase was purified to apparent homogeneity in a form that was deficient in heme. Heme-deficient guanylate cyclase was rapidly and easily reconstituted with heme by reacting enzyme with hematin in the presence of excess dithiothreitol, followed by removal of unbound heme by gel filtration. Bound heme was verified spectrally and NO shifted the absorbance maximum in a manner characteristic of other hemoproteins. Heme-deficient and heme-reconstituted guanylate cyclase were compared with enzyme that had completely retained heme during purification. NO and S-nitroso-N-acetylpenicillamine only marginally activated heme-deficient guanylate cyclase but markedly activated both heme-reconstituted and heme-containing forms of the enzyme. Restoration of marked activation of heme-deficient guanylate cyclase was accomplished by including 1 microM hematin in enzyme reaction mixtures containing dithiothreitol. Preformed NO-heme activated all forms of guanylate cyclase in the absence of additional heme. Guanylate cyclase activation was observed in the presence of either MgGTP or MnGTP, although the magnitude of enzyme activation was consistently greater with MgGTP. The apparent Km for GTP in the presence of excess Mn2+ or Mg2+ was 10 microM and 85-120 microM, respectively, for unactivated guanylate cyclase. The apparent Km for GTP in the presence of Mn2+ was not altered but the Km in the presence of Mg2+ was lowered to 58 microM with activated enzyme. Maximal velocities were increased by enzyme activators in the presence of either Mg2+ or Mn2+. The data reported in this study indicate that purified guanylate cyclase binds heme and the latter is required for enzyme activation by NO and nitroso compounds.
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PMID:Activation of purified guanylate cyclase by nitric oxide requires heme. Comparison of heme-deficient, heme-reconstituted and heme-containing forms of soluble enzyme from bovine lung. 612 34

Soluble guanylate cyclase activity from guinea pig heart is inhibited by increasing concentrations of sodium citrate. The Ki value was found to be 2.83 +/- 0.05 mM in the presence of 3 mM Mn2+ and 0.6 mM GTP. Citrate acts by lowering Vmax and increasing the apparent values of Km for GTP and K0.5 for Mn2+ and Mg2+. The soluble guanylate cyclase, activated by sodium nitroprusside, was also inhibited by citrate. This inhibitory action of citrate was not restricted to soluble guanylate cyclase activity of the heart and has been demonstrated also in the supernatant of lung, liver, diencephalon and in the homogenate of blood platelets. Since citrate is known to be an important intermediate of metabolism, its intracellular concentration may be also of relevance for guanylate cyclase activity.
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PMID:Inhibition of soluble guanylate cyclase activity by citrate. 612 48

Guanylate cyclase [EC 4,6,2,1] was found to be localized principally in the surface membrane (pellicle) of Tetrahymena pyriformis and to some extent in cilia, mitochondria and microsomes. In the pellicle fraction, guanylate cyclase activity with Mn2+ was higher than that with Mg2+. Addition of calmodulin and Ca2+ to the reaction mixture resulted in marked activation of guanylate cyclase with Mg2+ and Mn2+, but the extent of enhancement by calmodulin was greater with Mg2+ than with Mn2+. The activated enzyme could use either Mg2+ or Mn2+ as an equipotent cofactor.
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PMID:Calmodulin alters the cation requirement of membrane-bound guanylate cyclase in Tetrahymena. 612 37

The localization of guanylate cyclase activity was cytochemically studied in heart tissue from guinea pig and pigeon. The method, based on a lead precipitation technique with GPPNHP as the substrate, was tested by quantitative biochemical analysis. The data obtained showed that in heart homogenates GPPNHP is an acceptable substrate for guanylate cyclase. The guanylate cyclase activity of glutaraldehyde prefixed heart tissue was also measured in the presence of 2 mM lead nitrate, in 30% of the untreated control hearts. The residual guanylate cyclase responded to the addition of sodium nitroprusside with a 7-fold increase in its activity. Furthermore, the guanylate cyclase requirement for Mn2+ ions was so changed by this activator that Mg2+ was as active as Mn2+. In heart muscle cells of guinea pigs and pigeons the plasma membrane of the sarcolemma and the junctional sarcoplasmic reticulum are the precipitation sites of the reaction product. In guinea pig hearts the T-tubule membranes were likewise covered with precipitates. Sodium nitroprusside stimulation of guanylate cyclase activity was indicated by increased precipitation and by shortening of the incubation time.
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PMID:Cytochemical demonstration of guanylate cyclase activity in cardiac muscle. Preferential localization at sarcolemma and junctional sarcoplasmic reticulum. 613 98

In the presence of Mg-GTP, the rat liver guanylate cyclase, in either intact membranes or trypsin solubilized form, was stimulated by protoporphyrin IX 6 to 10-fold. However, when Mn-GTP was the substrate, protoporphyrin IX activated the membrane-bound guanylate cyclase only 50%, in contrast to the marked activation reported for the cytosolic enzyme. Meso- and deuteroporphyrin IX, hematoporphyrin and coproporphyrin III also activated membrane guanylate cyclase while uroporphyrin III, and hemin had no effect. Basal, Mg2+-dependent activity exhibited two classes of catalytic sites with apparent Km values of 2 mM and 0.12 mM. Activation by protoporphyrin resulted in the disappearance of the low affinity sites. The activated enzyme exhibited Michaelis-Menten kinetics and no alteration in its requirement for excess Mg2+. These data indicate that, in the presence of Mg2+, a heme-like structure can interact with the membrane-bound guanylate cyclase and regulate its activity.
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PMID:Protoporphyrin IX activates the Mg dependent guanylate cyclase from rat liver plasma membranes. 613 10


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