Synthesis of cGMP

There are two major families of guanylate cyclase, the particulate-associated enzymes, which are actually transmembrane receptors that contain guanylate cyclase within their intracellular domains, and the soluble type activated by NO (Kimura and Murad, 1974 Kuno et al., 1986 Schulz et al., 1991 Garbers, 1992 Schmidt et al., 1993). With more details of the structure and function of these enzymes, however, this strict division may become blurred. For example, NO-stimulated guanylate cyclase activity has been found to be associated with the membrane fraction of cells in some cases (Murad, 1994). 

The mechanism of activation of the receptor-type guanylate cyclases is not entirely clear. As is the case with other single-transmembrane domain receptor types, such as receptor-type tyrosine kinases, some sort of dimerization may be induced by ligand binding, which serves to activate the intracellular enzyme part of the receptor. As discussed in the next section, dimerization is essential to enzyme activity in soluble guanylate cyclases. 

The structure of this family of cyclases is distinct from the receptor type, the active enzyme being an a-/3 heterodimer of 76- and 80-kDa subunits, respectively (Kamisaki et al., 1986a Schmidt et al., 1993 Nakane and Murad, 1994). Although each subunit apparently contains catalytic and heme binding domains, enzyme activity is absolutely dependent on the presence of both subunits (Buechler et al., 1991 Schmidt et al., 1993 Nakane and Murad, 1994). The enzyme possesses a basal cyclase activity that is preferentially dependent on Mn, and activity is retained even in the absence 

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Onufriev, M.V., Gulyaeva, N.V., Terenina, N.B., Tolstenkov, O.O. and Gustafsson, M.K. (2005) The effect of a nitric oxide donor on the synthesis of cGMP in Hymenolepis diminuta a radiometric study. Parasitology Research 95, 22-24. 

NO-mediated synthesis of cGMP from GTP in the corpus cavernosum that leads to smooth muscle relaxation. Sildenafil potentiates the effects of NO by inhibiting cGMP phosphodiesterase. 

Synthesis of cGMP in vascular smooth muscle cells leads to activation of protein kinase G, which triggers a pathway leading to muscle relaxation and vasodilation. 

Cyclic GMP (cGMP) - Nitric oxide stimulates the synthesis of cGMP (see here). Many cells contain a cGMP-stimulated protein kinase that, like the cAMP-activated enzyme, contains both catalytic and regulatory subunits. 

Smooth muscle Nitric oxide is a powerful vasodilator in all vascular beds and a potent relaxant in most other smooth muscle tissues. The mechanism of this effect involves activation of guanylyl cyclase and the synthesis of cGMP. cGMP in turn facilitates the dephosphorylation and inactivation of myosin light chains, which results in relaxation of the muscle cells. Nitric oxide plays a physiologic role in erectile tissue function, in which smooth muscle relaxation is required to bring about the influx of blood that causes erection. 

The feedback effects of the ion movements on the two enzymes, diesterase and cyclase, which are respectively responsible for the hydrolysis during the excitation and the synthesis of cGMP during the recovery, are of particular interest. The cyclase reaction is inhibited by calcium and cGMP synthesis is accelerated when the Ca " concentration is decreased by closure of the ion channels. The calcium cycle and relaxation is another interesting story. 

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