M.Prasad NaiduMSc Medical Biochemistry,

Ph.D.Research Scholar

NONitric oxide possess more biological potential functions.Nitric oxide an uncharged molecule having an unpaired election.

It is highly free radical NOLipid soluble freely diffuse across half life is very short about 0.1 second.

SynthesisNO is synthesized from argenine by nitric oxide synthase (NOS).it is a dimeric proteincontain Heme

FADFMNTetrahydrobiopterineCalmodulin

The enzyme is dioxygenase

It utilizes molecular oxygenOne oxygen atom form NOOther 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.

Iso enzymes of Nitric oxide synthase.Three Isoforms from 3 different genes

Neuronal NOSNOSI or nNOS seen in central and peripheral neurons.Gene is on chromosome 12

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

it is a cytoplasmic enzyme but not activated by calcium .

Gene is on chromosome 17 .NOS 3 or endothelial NOS Gene is on chromosome 7Activated by calcium It is seen in endothelial cells , platelets

endocardium & myocardium .

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 .

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 .

NO in diseases & treatment1) Angina pectoris2) Pulmonary hypertention 3) Impotence 4) ShockAntagonists 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