cIMP: Synthesis, effector activation, inactivation and occurrence in biological systems

Background The soluble nitric oxide (NO)-stimulated guanylyl cyclase (sGC) uses GTP as a substrate to synthesize the secondary messenger cGMP [1]. However, sGC is not so stringent in terms of substrate-specificity and can also use ATP to produce yet another secondary messenger, cAMP [1]. Both cAMP and cGMP induce vasodilation. Recently, it has been proposed that under conditions of hypoxia, sGC predominantly produces cIMP to induce vasoconstriction [2]. Chemically, cGMP and cIMP are very closely related to each other, i.e. the only chemical difference between the two cyclic nucleotides is the missing amino group at the 2’-position of the purine ring (Fig. 1). How can such a small chemical difference between two molecules lead to opposite biological effects? To answer this question, we studied cIMP synthesis, effector activation, inactivation and biological occurrence.