[Soluble platelet guanylate cyclase: significance of heme in regulating enzymatic activity and the role of the enzyme in platelet aggregation].
The lability of the bond between the protein molecule of human platelet guanylate cyclase and heme (the prosthetic group of the enzyme) has been established. It was shown that soluble rat platelet guanylate cyclase exists in these cells originally in a heme-deficient form. The data obtained suggest that in contrast with the generally accepted view, heme is not the prosthetic group of this enzyme. The water-soluble antioxidant carnosine (beta-alanyl-L-histidine) inhibits the guanylate cyclase activation by sodium nitroprusside. This inhibitory effect is caused by carnosine interaction with the guanylate cyclase heme and can be used for evaluating the degree of the heme deficiency of the enzyme. Analysis of the mechanism of guanylate cyclase activation by nitroso complexes of some transient metals (Fe, Co, Cr) differing in the degree of NO oxidation demonstrated that the essential requirement for the realization of the hypotensive effect of these compounds is the activation of guanylate cyclase solely via a heme-dependent mechanism. The ADP-induced aggregation of human platelets (donors) is accompanied by enhanced stimulation of guanylate cyclase by various activators with a simultaneous increase in the intraplatelet cGMP level. This stimulation occurs irrespective of the involvement of the guanylate cyclase heme in the mechanism of enzyme regulation. It is concluded that guanylate cyclase acts via a negative feedback mechanism to control over platelet aggregation and mediates a signal to deaggregation. A hypothetic scheme for the regulatory role of cGMP in platelet aggregation is proposed.
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D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000201:enzymology*; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation; D006162:Guanylate Cyclase / Q000378:metabolism*; D006418:Heme / Q000172:deficiency / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D010084:Oxidation-Reduction; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D012995:Solubility
D006418:Heme; D000244:Adenosine Diphosphate; D006162:Guanylate Cyclase; D006152:Cyclic GMP
Rastvorimaia guanilattsikaza trombotsitob: znachenie gema v reguliatsii fermentativnoĭ aktivnosti, rol' fermenta v agregatsii trombotistov.