Nitric Oxide-Regulated Soluble Guanylate Cyclase

Nitric oxide plays significant roles in many physiological processes, and in most of these cases it works through activation of soluble guanylate cyclase and elevation of cyclic GMP concentration. Soluble guanylate cyclase is a heterodimeric protein made up of one a and one I² subunit. The beta subunit has one molecule of heme attached to it through a histidine moiety. NO activates the enzyme by binding to the heme Iron and weakening its bond to the histidine. The enzyme is deactivated upon dissociation of NO. Prolonged exposure to high concentrations of NO oxidizes heme or cysteines of the enzyme leading to inactivation and inability to respond upon Subsequent treatment with NO. In some cells, exposure to NO results in rapid desensitization of the enzyme, thus preventing undesirable consequences of continued, unabated cyclic GMP production.