Guanylate cyclase

Guanylate cyclase is an enzyme that catalyzes the conversion of guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP) and pyrophosphate. It is a part of the G protein signaling cascade and plays a crucial role in many physiological processes.

Structure

Guanylate cyclase exists in two forms: soluble guanylate cyclase (sGC) and membrane-bound guanylate cyclase (particulate guanylate cyclase, or pGC). Both forms are heterodimers, consisting of an alpha and a beta subunit. The alpha and beta subunits are each around 70-80 kDa and share a similar structure. The N-terminal domain of each subunit is highly variable, while the C-terminal domain is conserved and responsible for catalytic activity.

Function

The primary function of guanylate cyclase is to synthesize cGMP from GTP. cGMP acts as a second messenger, much like cyclic adenosine monophosphate (cAMP), in many physiological processes, including the regulation of vascular smooth muscle tone, neuronal signaling, and phototransduction in the retina.

Regulation

Guanylate cyclase activity is regulated by the concentration of intracellular calcium and by nitric oxide (NO). The binding of NO to the heme moiety of the beta subunit of sGC leads to a several hundred-fold increase in the enzyme's activity, leading to an increase in the intracellular concentration of cGMP.

Clinical significance

Mutations in the genes encoding the subunits of guanylate cyclase have been associated with several diseases, including Leber's congenital amaurosis, a severe form of inherited retinal degeneration, and pulmonary hypertension.

See also

• Guanosine triphosphate
• Cyclic guanosine monophosphate
• G protein
• Leber's congenital amaurosis
• Pulmonary hypertension