Everything about Cyclic Guanosine Monophosphate totally explained
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Cyclic guanosine monophosphate (
cGMP) is a
cyclic nucleotide derived from
guanosine triphosphate (GTP). cGMP acts as a
second messenger much like
cyclic AMP, most notably by activating intracellular
protein kinases in response to the binding of
membrane-impermeable
peptide hormones to the external cell surface.
Synthesis
cGMP synthesis is
catalyzed by
guanylate cyclase (GC), which converts
GTP to cGMP. Membrane-bound GC is activated by peptide hormones such as the
atrial natriuretic factor, while soluble GC is typically activated by
nitric oxide to stimulate cGMP synthesis.
Effects
cGMP is a common regulator of
ion channel conductance,
glycogenolysis, and cellular
apoptosis. It also relaxes
smooth muscle tissues. In
blood vessels, relaxation of vascular smooth muscles lead to
vasodilation and increased
blood flow.
cGMP is a secondary messenger in
phototransduction in the eye. In the photoreceptors of the mammalian eye, the presence of light activates
phosphodiesterase, which degrades cGMP. The
sodium ion channels in photoreceptors are cGMP-gated, so degradation of cGMP causes sodium channels to close, which leads to the hyperpolarization of the photoreceptor's plasma membrane and ultimately to visual information being sent to the brain.
Degradation
Cyclic nucleotide
phosphodiesterases (PDE 1-6) degrade cGMP by
hydrolyzing cGMP into 5'-GMP.
Phosphodiesterase inhibitors prevent the degradation of cGMP, thereby enhancing and/or prolonging its effects. For example,
Sildenafil (Viagra) enhances the vasodilatory effects of cGMP within the
corpus cavernosum by inhibiting PDE 5 (or PDE V). This is used as a treatment for
erectile dysfunction. However, the drug can inhibit PDE6 in retina with less affinity than PDE5, so it may lead blue vision.
Protein kinase activation
cGMP is involved in the regulation of some protein-dependent kinases. For example, PKG (
protein kinase G) is a
dimer consisting of one
catalytic and one regulatory unit, with the regulatory units blocking the
active sites of the catalytic units.
cGMP binds to sites on the regulatory units of PKG and activates the catalytic units, enabling them to phosphorylate their substrates. Unlike with the activation of some other protein kinases, notably PKA, the PKG is activated but the catalytic and regulatory units don't disassociate.
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