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)

Crude preparations of secretin or pancreozymin increased and at higher concentrations decreased guanylate cyclase (GTP pyophosphate-lyase, EC 4.6.1.2) activity from soluble and particulate fractions of rat liver homogenates. Partially purified and synthetic secretin were without effect as was the biologically active octapeptide fragment of pancreozymin. The active contaminants in these preparations survived boiling, saponification, and treatment with phospholipase A, trypsin and neuraminidase C. The activity was extractable with chloroform/methanol and did not survive ashing. Eight bile salt contaminants in crude secretin were obtained with thin-layer chromatography. Two of the contaminating bile salts that increased liver particulate guanylate cyclase activity were identified as taurodeoxycholate and either glycochenodeoxycholate or glycodeoxycholate; taurocholate was inhibitory. The sodium salts of cholate, deoxycholate, chenodeoxycholate and their glycine-or taurine-conjugated forms either increased or decreased particulate and soluble rat liver guanylate cyclase activity depending upon their concentration. Thus, the previously reported stimulatory and inhibitory effects of secretin and pancreozymin preparations on guanylate cyclase activity are probable attributable to their bile salt contaminants.
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PMID:Activation of liver guanylate cyclase by bile salts and contaminants in crude secretin and pancreozymin preparations. 1 19

Sodium azide, hydroxylamine, and phenylhydrazine at concentrations of 1 mM increased the activity of soluble guanylate cyclase from rat liver 2- to 20-fold. The increased accumulation of guanosine 3':5'-monophosphate in reaction mixtures with sodium azide was not due to altered levels of substrate, GTP, or altered hydrolysis of guanosine 3':5'-monophosphate by cyclic nucleotide phosphodiesterase. The activation of guanylate cyclase was dependent upon NaN3 concentration and temperature; preincubation prevented the time lag of activation observed during incubation. The concentration of NaN3 that resulted in half-maximal activation was 0.04 mM. Sodium azide increased the apparent Km for GTP from 35 to 113 muM. With NaN3 activation the enzyme was less dependent upon the concentration of free Mn2+. Activation of enzyme by NaN3 was irreversible with dilution or dialysis of reaction mixtures. The slopes of Arrhenius plots were altered with sodium azide-activated enzyme, while gel filtration of the enzyme on Sepharose 4B was unaltered by NaN3 treatment. Triton X-100 increased the activity of the enzyme, and in the presence of Triton X-100 the activation by NaN3 was not observed. Trypsin treatment decreased both basal guanylate cyclase activity and the responsiveness to NaN3. Phospholipase A, phospholipase C, and neuraminidase increased basal activity but had little effect on the responsiveness to NaN3. Both soluble and particulate guanylate cyclase from liver and kidney were stimulated with NaN3. The particulate enzyme from cerebral cortex and cerebellum was also activated with NaN3, whereas the soluble enzyme from these tissues was not. Little or no effect of NaN3 was observed with preparations from lung, heart, and several other tissues. The lack of an effect with NaN3 on soluble GUANYLATE Cyclase from heart was probably due to the presence of an inhibitor of NaN3 activation in heart preparations. The effect of NaN3 was decreased or absent when soluble guanylate cyclase from liver was purified or stored at -20degrees. The activation of guanylate cyclase by NaN3 is complex and may be the result of the nucleophilic agent acting on the enzyme directly or what may be more likely on some other factor in liver preparations.
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PMID:Activation of guanylate cyclase from rat liver and other tissues by sodium azide. 24 Aug 48

Purified virions of HVJ (Sendai virus) were found to contain a guanylate cyclase activity that converts GTP to cyclic GMP. Activities of adenylate cyclase and 5'-nucleotidase which are frequently used as marker enzymes of cell membranes were not detected in the virus. Guanylate cyclase and virion-associated activities, neuraminidase and hemagglutinin, were co-purified during a purification of virions. Guanylate cyclase activity was not detected without disruption of the virions with a detergent, Triton X-100 or Nonident P-40. Treatment of intact HVJ with a proteolytic enzyme, trypsin or chymotrypsin, destroyed both neuraminidase and hemagglutinin; however, most of the guanylate cyclase ws retained. Guanylate cyclase activity was found in fractions containing nucleocapsids after sucrose density gradient centrifugation of disrupted virions. These results indicated that the enzyme was tightly bound to cores of HVJ and, therefore, its presence could not be explained by binding of host cell enzyme to the surface of virions. Properties of the virus-derived enzyme and particulate fractions of host cell homogenates were similar. Antiserum against nucleocapsids of HVJ inhibited guanylate cyclase activity of HVJ and particulate fractions of cells such as chorioallantoic membrane and rat liver, while soluble guanylate cyclase was not inhibited by antiserum. The biological significance and origin of guanylate cyclase found in HVJ are obscure and await further study.
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PMID:Evidence for guanylate cyclase activity associated with hemagglutinating virus of Japan (Sendai virus). 610 29