The cyclic GMP, guanosine monophosphate also known as cyclic guanosine monophosphate or guanosine 3 of ', 5'-monophosphate is a nucleotide involved in numerous processes cyclic cell, especially those related signaling and intercellular communication.
It was described for the first time more than 40 years ago, shortly after the discovery of its analog, cyclic AMP, which differs from it in terms of the nitrogenous base, since it is not a nucleotide of guanine but of adenine.
Chemical structure of cyclic Guanosine monophosphate or GMP (Source: en: User: Diberri via Wikimedia Commons)
Like other cyclic nucleotides such as the aforementioned cyclic AMP or cyclic CTP (cyclic cytidine monophosphate), the structure of cyclic GMP is decisive for its chemical properties and biological activity, in addition to making it more stable than its counterpart.
This nucleotide is produced by an enzyme known as guanylyl cyclase and is capable of firing signaling cascades of cyclic-dependent GMP protein kinases, in a similar way to cyclic AMP.
It has been described not only in mammals, which are highly complex animals, but also in the simplest prokaryotes, included in the kingdoms of eubacteria and archaea. Its presence in plants is still a matter of debate, but evidence suggests that it is absent in these organisms.
Formation and degradation
The intracellular concentration of the cyclic guanine nucleotides, as well as that of adenine, is extremely low, especially when compared to their non-cyclic analogues that are mono-, di- or triphosphated.
However, the levels of this nucleotide can be selectively altered in the presence of certain hormonal stimuli and other factors that behave as primary messengers.
The metabolism of cyclic GMP is partially independent of the metabolism of cyclic AMP and other analogous nucleotides. This is produced from GTP by an enzyme system known as guanylyl cyclase or guanylate cyclase, which is a partially soluble enzyme in most tissues.
Guanylate cyclase enzymes are responsible for the "cyclization" of the phosphate group in position 5 'of the sugar residue (ribose), causing the binding of the same phosphate to two different OH groups in the same molecule.
This enzyme is very abundant in the small intestine and lungs of mammals and the most active source is found in the sperm of a species of sea urchin. In all the organisms that have been studied, it depends on divalent manganese ions, which differentiates it from adenylate cyclases, which depend on magnesium or zinc.
Cyclic GMP degradation is mediated by cyclic nucleotide phosphodiesterases that do not appear to be specific, since it has been shown that the same enzymes are capable of using both cyclic AMP and cyclic GMP as hydrolyzable substrates.
Both processes, formation and degradation, are carefully controlled intracellularly.
Structure
The structure of cyclic GMP is not significantly different from that of other cyclic nucleotides. As its name implies (guanosine 3 ', 5'-monophosphate) has a phosphate group attached to oxygen at the carbon at the 5' position of a ribose sugar.
Said ribose sugar is linked at the same time to the nitrogen base of the heterocyclic guanine ring by means of a glycosidic bond with the carbon in the 1 'position of ribose.
The phosphate group that is attached to the oxygen atom at the 5 'position of ribose is trans-fused through a phosphodiester bond, which occurs between the same phosphate group and the oxygen of the carbon at the 3' position of ribose, thus forming a 3'-5'- "trans-fused" phosphate (3'-5'- trans -fused phosphate).
The fusion of the phosphate group or its "cyclization" causes an increase in the rigidity of the molecule, since it restricts the free rotation of the bonds in the furan ring of ribose.
As is also true for cyclic AMP, the glycosidic bond between the guanine ring and ribose and its freedom of rotation are important structural parameters for the specific recognition of cyclic GMP.
Features
Unlike the many and highly varied functions that other analogous cyclic nucleotides such as cyclic AMP have, the function of cyclic GMP is a bit more restricted:
1-Participates in signaling processes in response to light stimulation of visual pigments. Its concentration is modified due to the activation of a G protein that perceives the light stimulus and interacts with a GMP-dependent cyclic phosphodiesterase.
Changes in the levels of this nucleotide alter the permeability of the membrane of the rod-shaped ocular cells to sodium ions, causing other changes that terminate the transmission of the stimulus to the optic nerve.
2-It has functions in the muscle contraction and relaxation cycle of smooth muscle in response to nitric oxide and other chemical compounds of various nature.
3-An increase in its concentration due to the response to natriuretic peptides is related to the regulation of the movement of sodium and water ions through cell membranes.
4-In some organisms, cyclic GMP can compete with cyclic AMP for cyclic nucleotide phosphodiesterase, and the addition of cyclic GMP can contribute to an increase in the concentration of cyclic AMP by reducing its degradation.
5-Bacteria such as E. coli increase their levels of cyclic GMP when exposed to chemo-attractants, indicating that this nucleotide is involved in signaling processes in response to these chemical stimuli.
6-It has been determined that cyclic GMP also has important implications in vasodilation and erection processes in mammals.
7-Many gate ion channels (calcium and sodium) are regulated by intracellular ligands that specifically use cyclic GMP.
References
- Botsford, JL (1981). Cyclic Nucleotides in Prokaryotes. Microbiological Reviews, 45 (4), 620–642.
- Garrett, R., & Grisham, C. (2010). Biochemistry (4th ed.). Boston, USA: Brooks / Cole. CENGAGE Learning.
- Hardman, J., Robison, A., & Sutherland, E. (1971). Cyclic nucleotides. Annual Reviews in Physiology, 33, 311–336.
- Nelson, DL, & Cox, MM (2009). Lehninger Principles of Biochemistry. Omega Editions (5th ed.).
- Newton, RP, & Smith, CJ (2004). Cyclic nucleotides. Phytochemistry, 65, 2423-2437.