Guanyl formation

Lydic, R., Garza-Grande, R., Struthers, R. Baghdoyan, H. A. (2006). Nitric oxide in B6 mouse and nitric oxide-sensitive soluble guanylate cyclase in cat modulate acetylcholine release in pontine reticular formation. J. Appl. Physiol 100, 1666-73. 

Feelisch, M., Noack, M., Correlation between nitric oxide formation during degradation of organic nitrates and activation of guanylate cyclase. Eur. J. Pharmacol. 139 (1987), p. 19-30... 

Ozawa N, Guengerich FP. 1983. Evidence for formation of an S-[2(N -guanyl]ethyl) glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA. Proc Natl Acad Sci USA 80 5266-5270. 

Fig. 1. Nitric oxide (NO) synthesis by nitric oxide synthase (NOS) (upper left), NO reaction with soluble guanylate cyclase (sGC) (middle), and formation of cyclic GMP, which causes tissue-specific signaling (right). The roles of the salivary nitrophorins from Rhodnius prolixus in storing and releasing NO and binding histamine are included (lower left).

While it is clear that NO is involved in the EDRF, there is also evidence that conjugation with thiols may occur as intermediates [47]. In 1981, Ignarro observed that NO-donating vasodilators react with cysteine to form S-nit-rosocysteine, an activator of guanylate cyclase, and suggested that the formation of unstable S-nitrosothiols was involved in the biological function of nitric oxide... 

The ability of coordinated NO to react with thiols has led to the suggestion of an alternative mechanism for activating guanylate cyclase. This involves nitroprusside oxidation of protein sulfhydryls to cross-link the protein with a disulfide bridge. For example, papain, which has an essential cysteine (cys-25) and glyceradehyde-3-phosphate dehydrogenase (cys-149) are both inhibited by nitroprusside with formation of [Fe(CN)5(NO)] and [Fe(CN)4NO] [132]. The suggested anaerobic reaction is ... 

Since hemoproteins such as lactoperoxidase and catalase are inhibited more rapidly than the sulfhydryl oxidation occurs, it is unlikely that the rapid activation of guanylate cyclase occurs by sulfhydryl oxidation [132]. Prolonged incubation of the papain or dehydrogenase enzymes with substrate and nitroprusside yielded a turbidity which indicated denaturation of the enzyme to an insoluble form, possibly by the formation of disulfide bridges via the dimerization of thiyl radicals [132]. 

Another possibility that deserves further investigation is the formation of a transient and reversible complex of nitric oxide and oxygen to yield the nitro-syldioxyl radical (ONOO ) The nitrosyldioxyl radical may be stabilized by hydrogen bonding to water, which may prevent it from activating guanylate cyclase (Beckman and Koppenol, 1992). 

Schematic illustration of the interrelationships between glutamate and NO in synaptic function in the cetebellum. The presynaptic nerve terminal synthesizes, stores, and releases glutamate (G) as the neurotransmitter by exocytosis as illustrated. The glutamate diffu.ses across the synaptic cleft and interacts with postsynaptic NMDA recepti>rs ( ) that are coupled to calcium (Ca ) channels. Ca influx occurs and the free intracellular Ca complexes with calmtxlulin and activates NO synthase. NADPH is also required hir conversion, and the products of the reaction are NO plus L-citrulline. NO diffuses out of the piistsynaptic cell to interact with nearby target cells, one of which is the presynaptic neuron that released the glutamate in the first place. NO stimulates cytosolic guanylate cyclase and cyclic GMP (cGMP) formation presynaptically, hut the consequence of this pre.synaptic modification is unknown.

Knowles, R. G., Palacios, M., Palmer, R. M. J., and Moncada, S. (1989). Formation of nitric oxide from L-arginine in the central nervous system A transducer mechanism for stimulation of the soluble guanylate cyclase. Proc. Natl. Acad. Sci. U.S.A. 86, 5159-5162. 

GMP <2, 7> (<2> competitive inhibitor to dGMP [2] <7> non competitive with respect to MgATP because of the formation of an abortive complex guanylate kinase-MgATP "GMP [18]) [2, 18]... 

The formation of guanyl azide (IV) at the first stage may account for the formation of tetrazene by the action of nitrous acid on aminoguanidine, i.e. by Hoffmann synthesis. 

Foureman, GL. Reed, D.J. (1987) Formation of 5-[2-(V7-guanyl)ethyl] adducts by the postulated 5 -(2-chloroethyl)cysteinyl and S-(2-chloroethyl)glutathionyl conjugates of 1,2-dichloroethane. Biochemistry, 26, 2028-2033... 

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