CGMP, second messenger

Cyclic nucleotides (cAMP and cGMP) are formed enzymatically from the corresponding triphosphates. As ubiquitous second messengers, they mediate many cellular functions which are initiated by first (extracellular) messengers. Their prime targets in eucaryotic cells are protein kinases ( cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase), ion channels and ensymes. 

Guanylyl cyclases (GC) are a family of enzymes (EC 4.6.1.2) that catalyse the formation of the second messenger cyclic GMP (cGMP) from guanosine triphosphate (GTP). GCs are subdivided in soluble GCs and GCs that are membrane-bound and linked to a receptor. Activation occurs by nitric oxide (NO) and pqrtide hormones, respectively [1,2]. 

The enzyme guanylyl cyclase produces the second messenger guanosine monophosphate (3, 5 -cyclic GMP, cGMP) from guanosine triphosphate (GTP). 

Figure 10. The G-protein cascades in smooth muscle catalyze the exchange GDP for GTP on G-protein. Following the binding of GTP, the trimeric G-protein splits into an a-GTP part and a P-y part. The a-GTP part ordinarily then combines with its specific apoenzyme to constitute the active enzyme. For the activation of the contractile activation path, the enzyme is phospholipase C and the second messenger products are IP3 and DAG. The IP3 in the myoplasm binds to Ca channels in the SR membrane, opening them. Other second messengers include the inhibitors of contractile activity, cGMP and cAMP.

Nucleoside triphosphates have high group transfer potential and participate in covalent bond syntheses. The cyclic phosphodiesters cAMP and cGMP function as intracellular second messengers. 

The mechanisms by which cyclic GMP produces its physiological effects are more varied. It has been more difficult to identify second messenger actions of cGMP compared to cAMP. This probably reflects the lower concentrations of cGMP in most tissues and the likelihood that cGMP plays a less widespread role in cell function. 

Among the best studied protein kinases in the brain are those activated by the second messengers cAMP, cGMP, Ca2+ and DAG [4,5]. 

Protein kinases, in cooperation with other proteins, form multiprotein complexes which are susceptible to activation upon external agonist stimuli. According to different functions in cell-cycle regulation, the conformational changes are initiated by autophosphorylation and dimerization transmitted by the previously discussed second messengers cAMP, cGMP, IP3, PIP3, AA and DAG. 

G-proteins are so called because they bind a guanosine nucleotide, either GTP or GDP. Their transduction mechanism involves the production of a second messenger such as 3 5 cAMP, 3 5 cyclic GMP (cGMP) or IP3 and diacylglycerol (DAG), derived from AMP, GMP and phosphatidyl inositol-3,5bisphosphate respectively (Figure 4.15). It is the second messenger that initiates the downstream amplification process phase of transduction. 

NO is a gas that diffuses freely through cell membranes. Once inside its target cell, NO binds directly with and activates guanylyl cyclase, an enzyme that converts GTP into cGMP cGMP is a second messenger for a number of tissue specific processes in neurones, smooth muscle and white blood cells. 

A number of the actions of NO in target cells may be explained by its binding to the haem-containing protein soluble guanylyl cyclase (sGC), an enzyme which generates a second messenger, cyclic GMP (cGMP) from GTP. 

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