M.

Prasad Naidu
MSc Medical Biochemistry,
Ph.D.Research Scholar

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.
Synthesis
NO is synthesized from argenine by nitric oxide synthase
(NOS).
it is a dimeric protein
contain Heme
FAD
FMN
Tetrahydrobiopterine
Calmodulin
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 (O
2
-
) 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 NOS
NOSI 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 NOS
Macrophage 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 7
Activated 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 &
Hirschsprungs 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 & treatment
1) Angina pectoris
2) Pulmonary hypertention
3) Impotence
4) 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