Guanylate cyclase

Guanylate cyclase (EC 4.6.1.2, also known as guanylyl cyclase, guanyl cyclase or GC) is a lyase enzyme.

Reaction

Guanylate cyclase catalyzes the reaction of guanosine triphosphate (GTP) to 3',5'-cyclic guanosine monophosphate (cGMP) and pyrophosphate:

• 

  GTP

• 

  cGMP

Types

There are membrane-bound (type 1, guanylate cyclase-coupled receptor) and soluble (type 2, soluble guanylyl cyclase) forms of guanylyl cyclases. Membrane bound guanylyl cyclases include an external ligand binding domain (e.g., for peptide hormones such as BNP and ANP), a transmembrane domain, and an internal catalytic domain homologous to adenate cyclases ^[1]. Soluble guanylate cyclase contains a molecule of heme, and is primariy activated by the binding of nitric oxide (NO) to that heme ^[2]). Other activators include YC-1 and carbon monoxide. ^[3]. See Carbon monoxide#Medicine. The 'soluble' isoforms can be associated with membranes and with large protein assemblies (e.g., at synapses).

Function

Like cAMP, cGMP is an important second messenger that internalizes the message carried by intercellular messengers such as peptide hormones and NO, and can also function as an autocrine signal. Depending on cell type, it can drive adaptive/developmental changes requiring protein synthesis. In smooth muscle, cGMP is the signal for relaxation, and this it is coupled to many homeostaic mechanisms including regulation of vascular and airway tone, insulin secretion, and peristalsis. Once formed, cGMP can be degraded by phosphodiesterases, which themselves are under different forms of regulation, depending on the tissue.

Like cAMP, cGMP is known to regulate many cellular proteins, such as protein kinases, ion channels, and phosphodiesterases.

See also

• Guanylate cyclase activator (protein)

References

1. ^ 1) Kuhn, M. Structure, Regulation, and Function of Mammalian Membrane Guanylyl Cyclase Receptors, With a Focus on Guanylyl Cyclase-A CIRCULATION RESEARCH 2003, VOL 93; PART 8, pages 700-709
2. ^ Derbyshire ER; Marletta MA. Biochemistry of soluble guanylate cyclase. Handb. Exp. Pharmacol. 2009, 191, 17-31. Rev.
3. ^ http://www.nytimes.com/1993/01/26/science/carbon-monoxide-gas-is-used-by-brain-cells-as-a-neurotransmitter.html?pagewanted=3&src=pm

External links

• MeSH Guanylate+Cyclase