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NITRIC OXIDE

BIOCHEMISTRY

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NITRIC OXIDE

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  1. NITRIC OXIDE M.Prasad Naidu MSc Medical Biochemistry, Ph.D.Research Scholar

  2. NO Nitric oxide possess more biological potential functions. Nitric oxide an uncharged molecule having an unpaired election. It is highly free radical NO Lipid soluble freely diffuse across half life is very short about 0.1 second.

  3. Synthesis NO is synthesized from argenine by nitric oxide synthase (NOS). it is a dimeric protein contain Heme FAD FMN Tetrahydrobiopterine Calmodulin

  4. The enzyme is dioxygenase It utilizes molecular oxygen One oxygen atom form NO Other in corporated into citrulline NO reacts with oxygen Nitrite Excreted in the urine Reacts with Haemoglobin NO is Nitrates On exposed to superoxide (O2-) nitric acid No & peroxynitrite (OONO) Causes lipid peroxidation ; cell injury and cell death.

  5. Iso enzymes of Nitric oxide synthase. Three Isoforms from 3 different genes Neuronal NOS NOSI or nNOS seen in central and peripheral neurons. Gene is on chromosome 12

  6. Nitrogenic neurons are seen especially in cerebellum and gastrointestinal tract, Cytoplasmic enzyme activated by calcium. Macrophage NOS , NOS2 or inducible NOS Macrophage NOS is mostly present in macrophages & neutrophils. To a lesser extent present in hepatocytes . it is induced by cytokines & during inflammatory reactions

  7. it is a cytoplasmic enzyme but not activated by calcium . • Gene is on chromosome 17 . • NOS 3 or endothelial NOS • Gene is on chromosome 7 • Activated by calcium • It is seen in endothelial cells , platelets endocardium & myocardium .

  8. Localized in plasma membrane . • Activated by calcium . • Functions of Nitric oxide : 1)On blood vessels potent vasodilator Decreased concentration of nitric oxide leads to hypertention . NOS is seen only in arterioles not in venules. 2)Platelets : inhibits adhesion of platelets . 3)GIT : NO is nonadrenergic non cholinergic neurotransmitter in GIT & urinarytract .

  9. Reduces gastric motility & relaxes sphincters . • Infantile hypertrophic pyloric stenosis & Hirschsprung’s disease • Nitric oxide is considered as a memory molecule . • NO stimulates release of hormones like CRH , GNRH , LHRH . • In macrophage NO production is induced by interleukin & tumor necrosis factor .

  10. NO in diseases & treatment • Angina pectoris • Pulmonary hypertention • Impotence • Shock Antagonists of NO : N- Mono methyl arginine ( NMMA ), competitively inhibits NOS . Asymmetric dimethyl arginine ( ADMA ) arginine analogue acts as NOS inhibitor . Increased in hyperhomocysteinemia & preeclampsia – increased B.P

  11. Thank you

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