Soluble guanylate cyclase (sGC) (sGC)

Soluble guanylate cyclase (sGC) is a heterodimeric enzyme that serves as the primary intracellular receptor for nitric oxide (NO) [1]. It consists of alpha and beta subunits and contains a prosthetic heme group that binds NO with high affinity [1, 2]. Upon activation, sGC catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP), a potent second messenger that regulates vascular tone, platelet reactivity, and cardiac remodeling through downstream effectors like protein kinase G (PKG) [2, 3]. The broader nitrate-nitrite-NO pathway involves the sequential reduction of inorganic nitrate to nitrite and then to NO, which subsequently activates sGC [4]. Dysregulation of this pathway, often characterized by reduced NO bioavailability or sGC oxidation, is a hallmark of cardiovascular diseases such as pulmonary arterial hypertension (PAH) and heart failure [3, 5]. Pharmacological agents like riociguat and vericiguat are used to treat these conditions by enhancing cGMP production even when NO levels are low [5, 6].

Other names

Guanylyl cyclase (soluble)NO-sensitive guanylyl cyclaseGUCY1A1GUCY1B1Nitrate-nitrite-nitric oxide pathway

Soluble guanylate cyclase (sGC) stimulators bind to the native enzyme to stabilize the NO-heme-sGC complex and increase cGMP production, while sGC activators target the oxidized or heme-free form of the enzyme to restore signaling under oxidative stress conditions [3, 5]. NO donors like nitroglycerin release nitric oxide, which then binds to the heme group of sGC to activate it [4].