Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Partially purified soluble rat liver guanylate cyclase [GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] was activated by superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1). This activation was prevented with KCN or glutathione, inhibitors of superoxide dismutase. Guanylate cyclase preparations formed superoxide ion. Activation by superoxide dismutase was further enhanced by the addition of nitrate reductase. Although guanylate cyclase activity was much greater with Mn2+ than with Mg2+ as sole cation cofactor, activation with superoxide dismutase was not observed when Mn2+ was included in incubations. Catalase also decreased the activation induced with superoxide dismutase. Thus, activation required the formation of both superoxide ion and H2O2 in incubations. Activation of guanylate cyclase could not be achieved by the addition of H2O2 alone. Scavengers of hydroxyl radicals prevented the activation. It is proposed that superoxide ion and hydrogen peroxide can lead to the formation of hydroxyl radicals that activate guanylate cyclase. This mechanism of activation can explain numerous observations of altered guanylate cyclase activity and cyclic GMP accumulation in tissues with oxidizing and reducing agents. This mechanism will also permit physiological regulation of guanylate cyclase and cyclic GMP formation when there is altered redox or free radical formation in tissues in response to hormones, other agents, and processes.
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PMID:Activation of guanylate cyclase by superoxide dismutase and hydroxyl radical: a physiological regulator of guanosine 3',5'-monophosphate formation. 2 77

The mechanism of activation of soluble guanylate cyclase purified from bovine lung by phenylhydrazine is reported. Heme-deficient and heme-containing forms of guanylate cyclase were studied. Heme-deficient enzyme was activated 10-fold by NO but was not activated by phenylhydrazine. Catalase or methemoglobin enabled phenylhydrazine to activate guanylate cyclase 10-fold and enhanced activation by NO to over 100-fold. Heme-containing enzyme was activated only 3-fold by phenylhydrazine but over 100-fold by NO. Added hemoproteins enhanced enzyme activation by phenylhydrazine to 12-fold without enhancing activation by NO. Reducing or anaerobic conditions inhibited, whereas oxidants enhanced enzyme activation by phenylhydrazine plus catalase, and KCN had no effect. In contrast, enzyme activation by NO and NaN3 was inhibited by oxidants or KCN. NaN3 required native catalase, whereas phenylhydrazine also utilized heat-denatured catalase for enzyme activation. Thus, the mechanism of guanylate cyclase activation by phenylhydrazine differed from that by NO or NaN3. Guanylate cyclase activation by phenylhydrazine resulted from an O2-dependent reaction between phenylhydrazine and hemoproteins to generate stable iron-phenyl hemoprotein complexes. These complexes activated guanylate cyclase in the absence of O2, but lost activity after acidification, basification, or heating. Gel filtration of prereacted mixtures of [U-14C]phenylhydrazine plus hemoproteins resulted in co-chromatography of radioactivity, protein, and guanylate cyclase stimulating activity, and yielded a phenyl-hemoprotein binding stoichiometry of four under specified conditions (one phenyl/heme). [14C]Phenyl bound to heme-containing but not heme-deficient guanylate cyclase and binding correlated with enzyme activation. Moreover, reactions between enzyme and iron-[14C] phenyl hemoprotein complexes resulted in the exchange or transfer of iron-phenyl heme to guanylate cyclase and this correlated with enzyme activation.
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PMID:Guanylate cyclase from bovine lung. Evidence that enzyme activation by phenylhydrazine is mediated by iron-phenyl hemoprotein complexes. 614 58