NÎTRÎK OKSÎTİN SENTEZİ VE BİYOLOJİK ÖNEMİ

Yıl 2006, Cilt: 9 Sayı: 2, 27 - 32, 01.06.2006

Ayşegül Bildik

Öz

Yalnızca atmosferde kirlenmeye neden olduğu düşünülen nitrik oksit gazının, memeli hücreleri tarafından üretildiğinin anlaşılmasından sonra bir çok biyolojik olay hakkında önemli bilgiler elde edilmiştir. Nitrik oksit NO , arginin aıninoasitinden sitrüilin şekillenmesi sırasmda Nitrik oksit sentaz NOS enzimi aracılığıyla sentezlenir. NOS’ın farklı genler tarafından kodlanan üç izoformu vardır: Uyarılabilir NOS İNOS , makrofajlarda tümör ve bakteri hücrelerini öldürmek, damar endotel hücrelerinde bulunan endotelyal NOS eNOS ise kan damarlarının gevşemesi için, sinir hücrelerinde lokalize olan nöronal NOS nNOS da nörotransmiter olarak NO üretir. eNOS ve nNOS, kalsiyum ile kalmoduline bağlıdır. Reseptörlerin uyarılması için pikomol miktarlarda NO sentezler. Bununla beraber İNOS kalsiyumdan bağımsızdır ve nanomol düzeyinde NO üretir. NOS, L-arginin analogları tarafından inhibe edilir

Anahtar Kelimeler

Arginin, Nitrik oksit, Nitrik oksit sentaz

BİOLOGİCAL ACTİVİTY AND SYNTHESİS OF NİTRİC OXİDE

Öz

zThe understand that mammalian cells generate nitric oxide NO , a gas previously thought to be only an atmospheric pollutant, is providing important information about many biological process. NO is formed by nitric oxide synthase NOS oxidizing arginine to NO with the formation of citrulline. Three distinct gene codes for the three forms of NOS: inducible NOS İNOS , whose induced synthesis enables macrophages to form the NO that kills tumor cells and bacteria, endothelial NOS eNOS , which produces the NO that relaxes blood vessels, and neuronal NOS nNOS , which as neurotransmitter. İNOS and nNOS are calcium and calmodulin-depent, andrelease picomoles of nitric oxide in response to receptor stimulation. However İNOS is calcium-independent and release nanomol of nitric oxide. NOS is inhibited by L-arginine analogues

Anahtar Kelimeler

Arginine, Nitric oxide, Nitric oxide synthase

Kaynakça

• 1- Korshland D.E., Nitric oxide, the molecule of the year. Science, 258:1861, (1992).
• 2- Moncada S., Palmer R.M.J., Higgs E.A. :The biological signifîcance of nitric oxide formation from L-arginine. Biochemical Society Transactions, 17,4:642-644, (1989).
• 3- Furchgott R.F., Zawadzki J.V.: The obligatory role of the endothelial cells in the relaxation of arterial smooth muscleby acethylcholine.Nature,288:373-75, (1980).
• 4- Furchgott R.F.: The discovery of endothelium derived relaxing factor and its importance in the Identification of nitric oxide. J.Amer.Med.Assoc.,276:1186, (1996).
• 5- Ignarro L.J., Buga G.M., Wood K.S., Byms R.E., Chaudhuri G.: Endothelium derived relaxing factor produced and released from artery and vein is nitric oxide. Proc.Natl.Acad. Sci., 84:9265-70, (1987).
• 6- Moncada S., Palmer R.M.J., Higgs E.A.: Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol.Rev.43:109-142,(1991).
• 7- Forstermann U., Properties and mechanisms of production and action of endothelium-derived relaxing factor. J.Cardiovasc. Pharmacol. 8 (10): 45-51, (1986).
• 8- Guoyao W.U., Sidney M.Morris M.: Arginine metabolism: nitric oxide andbeyond, Biochem J.,336:1-17, (1998).
• 9- Fukuto J.M., Hobbs A.J., Ignarro L.J.: Conversion of Nitroxyl (HNO) to Nitric oxide (NO) in biological Systems: The role of physiological oxidants and relevance to the biological activity of HNO. Biochemical and biophysical research Communications, 196(2):707- 713,(1993).
• 10- Hardy T.A., May J.M.: Coordinate Regulation of LArginine uptake and nitric oxide synthase activity in cultured endothelial cells. Free Radical Biology &Medicine, 32(2): 122-131,(2002).
• 11- Stuehr D., J.: Mammalian nitric oxide synthases, Biochem., J., 357: 593-615, (2001).
• 12- Moncada S., Higgs E.A.: Molecular mechanisms and therapeutic strategies related to nitric oxide. FASEB J., 9(13); 1319-30,(1995).
• 13- Vilar R.E., Ghael D., Li M., Bhagat D.D., Arrigo L.M., Cowman M.K., Dweck, H.S., Rosenfeld L.: Nitric oxide degradation of heparin and heparan sulphate. Biochem J., 324:473-479, (1997).
• 14- Masters B.S.S.: Nitric oxide synthases: why so complex? Annu.Rev. ,Nutr., 14:131-45, (1994).
• 15- Baranano D.E., Snyder S.H.: Neural roles for heme oxygenase: Contrasts to nitric oxide synthase, PNAS 98(20): 10996-11002,(2001).
• 16- Alderton W.K., Cooper C.E., Knowles R.G.: Nitric oxide synthases:structure, function and inhibition, Biochem J., 357:593-615, (2001).
• 17- Vallance P.: Use of L-Arginine and Its analogs to study Nitric oxide pathways in humans. Methods in Enzymology, 269:453-459,(1996).
• 18- Dwyer M.A., Bredt D.S., Synder S.H.: Nitric oxide synthase: Irreversible inhibition by L-NG nitro-arginine in brain in vitro and in vivo. Biochem. Biophys. Res. Commun. 176:1136-1141,(1991).
• 19- Moncada S.: The L-arginine :nitric oxide pathway. Açta Physiol Scand, 145:201-227, (1992).
• 20- Morıcada S., Higgs A.: The L-arginine-nitric oxide Pathways. The New England Journal of Medicine, 30: 2002-2011,(1993).
• 21- Bredt D.S., Synder S.N.: Nitric oxide mediates glutamatelinked enhancement of cGMP levels in the cerebellum. Proc.Natl.Acad.Sci., 86:9030-9033,(1989).
• 22- Bidri M., Feger F., Varadaradjalou S., Ben Hamouda N., Guillosson J.J., Arock M.: Mast cells as a source and target for nitric oxide. Int Immunopharmacol, (8): 1543- 58,(2001).
• 23- Di Rosa M., Radomski M., Camuccio R., Moncada S.: Glucocorticoids inhibit the induction of nitric oxide synthase in macrophages. Biochem Biophy. Res. Commun., 172:1246-1252,(1990).
• 24- Gow A.J., Luchsinger B.P., Pawloski J.R., Singel D.J., Stamler J.S.: The oxyhemoglobin reaction of nitric oxide. ProcNatl Acad Sci, 96:9027-9032, (1999).
• 25- Li, H., Forstermann U.: Nitric oxide in the pathogenesis ofvascular disease. J.Pathol., 190:244-254, (2000).
• 26- Radomski M.W., Palmer R.M.J., Moncada S.: The role of nitric oxide and cGMP in platelet adhesion tı vascular endothelium. Biochem.Biophys. Res. Commun, 148: 1482- 1489,(1987).
• 27- Wang M.X., Murrell D.F., Szabo C., Warren R.F.,Sarris M., Murrell G.A.: Nitric oxide in skeletal muscle: inhibition of nitric oxide synthase inhibits walking speed inrats. Nitric oxide 5(3):219-32, (2001).
• 28- Moncada S., Radomski M.W., Palmer R.M.J., Endothelium derived relaxing factor. Identification as nitric oxide and role in the control of vascular tone and platelet function. Biochem.Pharmacol. 37: 2495- 2501,(1988).
• 29- Chapman P.F., Atkins C.M., Ailen M.T., Haley J.E., Steinmetz J.E.: inhibition of nitric oxide synthesis impairs two different forms of leaming. Neuroreport, 3: 567- 70,(1992).
• 30- Vallance P., Moncada S., Coll J.R.: Nitric oxide from mediator to medicine. Physcians, 28 (3): 209-19, (1994).
• 31- Ignarro L.J., Bush P.A., Buga G.M., Wood K.S., Fukuto J.M., Rajfer J.: Nitric oxide and cyclic GMP formation upon electrical fıeld stimulation cause relaxation of corpus cavemosum smooth muscle. Biochem. Biophys Res. Commun, 170: 843-50,(1990).
• 32- Burmett A.L., Lowenstein C,J. Biedt D.S., Chang T.S.K., Synder S.H.: Nitric oxide: a physiologic mediator of penile erection. Science, 257:401-403, (1992).
• 33- Schmidt K., Wemer-Felmayer G., Mayer B., Wemer E.R. :Preferential inhibition of inducible nitric oxide synthase in intact cells by the 4-amino analogue of tetrahydrobiopterin. Eur.J.Biochem., 259(1-2): 25-31, (1999).
• 34- Stuehr D.J., Kwon N.S., Nathaon C.F.: FAD and GSH participate in macrophage synthesis of nitric oxide. Biochem biophys. Res. Commun., 30,168(12): 558-65, (1990).
• 35- Coleman J.W.: Nitric oxide in immunity and inflammation. Int Immunopharmacol, 1(8): 1397-406, (2001).