Soluble guanylate cyclase alpha-1 and beta-1 subunits (sGC) (sGC)

Soluble guanylate cyclase (sGC) is a heterodimeric enzyme, typically composed of alpha-1 (GUCY1A1) and beta-1 (GUCY1B1) subunits, that serves as the primary intracellular receptor for nitric oxide (NO) [1, 4, 11]. Upon binding NO to its prosthetic heme group, sGC catalyzes the conversion of guanosine triphosphate (GTP) into the second messenger cyclic guanosine monophosphate (cGMP), which regulates vascular tone, inhibits platelet aggregation, and prevents pathological remodeling [3, 5, 13]. Dysregulation of the NO-sGC-cGMP pathway is a key driver in diseases such as pulmonary arterial hypertension (PAH), heart failure, and chronic thromboembolic pulmonary hypertension (CTEPH) [10, 12]. Pharmacological targeting of sGC includes stimulators like riociguat and vericiguat, which sensitize the enzyme to NO, and activators like cinaciguat, which restore activity in heme-deficient or oxidized states [6, 7, 9]. Beyond cardiovascular roles, sGC subunits have been implicated in stroke recovery, atherosclerosis, and certain cancers, where they may influence cell proliferation and survival [15, 16, 2]. These therapeutic interventions aim to restore cGMP signaling to promote vasodilation and provide organ protection in patients with compromised NO bioavailability [17].

Other names

sGCGuanylate cyclase 1 soluble subunit alpha 1Guanylate cyclase 1 soluble subunit beta 1GUCY1A1GUCY1B1GUCY1A3GUCY1B3Nitric oxide receptorGuanylyl cyclase alpha-1/beta-1

Soluble guanylate cyclase (sGC) stimulators and activators increase the production of cyclic guanosine monophosphate (cGMP) from GTP. Stimulators (e.g., riociguat) act on the reduced heme-containing enzyme to sensitize it to nitric oxide (NO) and provide direct stimulation [5, 9]. Activators (e.g., cinaciguat) target the heme-free or oxidized form of the enzyme to restore its activity in states of oxidative stress [7, 12]. Both mechanisms lead to increased cGMP levels, promoting vasodilation and organ protection [10].