Soluble guanylyl cyclase (sGC) (sGC)

Soluble guanylyl cyclase (sGC) is a key signal-transduction enzyme and the primary intracellular receptor for nitric oxide (NO) (UniProt P14314). It is a heterodimer typically composed of alpha and beta subunits, containing a prosthetic heme moiety that binds NO to catalyze the synthesis of cyclic guanosine monophosphate (cGMP) from GTP (PMID: 28215460). The resulting cGMP acts as a second messenger that regulates various physiological processes, most notably the relaxation of vascular smooth muscle and the inhibition of platelet aggregation. In conditions like pulmonary arterial hypertension and heart failure, the NO-sGC-cGMP pathway is often impaired due to reduced NO bioavailability or oxidative stress (PMID: 23883558). Pharmacological intervention often involves NO donors, such as nitroglycerin, which release NO to activate sGC, or direct sGC stimulators like riociguat that enhance the enzyme's sensitivity to NO (PMID: 33113324). These therapies are designed to restore normal cGMP signaling to alleviate vasoconstriction and prevent adverse cardiac remodeling. By targeting sGC, these drugs provide a critical mechanism for managing cardiovascular resistance and improving patient hemodynamics.

Other names

Guanylate cyclase (soluble)NO-sensitive guanylyl cyclaseGUCY1A3/GUCY1B3 complexGTP pyrophosphate-lyase (cyclizing)Guanylate cyclase soluble subunit alpha-3/beta-3

Activation of sGC by nitric oxide (either endogenous or released from prodrugs) triggers the conversion of GTP to cGMP, which activates protein kinase G (PKG) to mediate smooth muscle relaxation and vasodilation (StatPearls: Nitroglycerin).