Soluble guanylate cyclase α1β1 isoform (sGC α1β1)

Soluble guanylate cyclase (sGC) is a heterodimeric enzyme that serves as the primary intracellular receptor for nitric oxide (NO). The α1β1 isoform is the most widely distributed and physiologically significant form of the enzyme, composed of an α1 subunit (GUCY1A3) and a β1 subunit (GUCY1B3) [1, 7]. Upon binding of NO to its prosthetic heme group, sGC catalyzes the conversion of guanosine triphosphate (GTP) to the second messenger cyclic guanosine monophosphate (cGMP) [16, 19]. This signaling cascade mediates critical physiological processes, including vascular smooth muscle relaxation, inhibition of platelet aggregation, and suppression of cardiac and vascular remodeling [4, 6]. Impairment of the NO-sGC-cGMP pathway is a hallmark of various cardiovascular and pulmonary diseases, such as pulmonary arterial hypertension and heart failure [9, 12]. Therapeutic strategies targeting this isoform include sGC stimulators, which enhance the enzyme's sensitivity to NO, and sGC activators, which can activate the enzyme even in its oxidized or heme-free states [12, 13]. While effective in improving hemodynamics and exercise capacity, these drugs are associated with safety concerns such as systemic hypotension and syncope [8, 9].

Other names

Guanylate cyclase 1 soluble subunit alpha 1/beta 1GC-1sGCGCSNitric oxide receptorGUCY1A3/GUCY1B3 heterodimer

Soluble guanylate cyclase stimulators (sGCs) sensitize the enzyme to endogenous nitric oxide (NO) and directly stimulate the enzyme in a NO-independent manner, while sGC activators (sGCa) target the oxidized or heme-free form of the enzyme to restore cGMP production under conditions of oxidative stress [12, 13].