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NItric Oxide (NO)

• NO is a free radical gas
• GAS SECOND MESSENGERS CAN DIFFUSE THROUGH BOTH THE CYTOSOL AND THE PLASMA MEMBRANE
• this makes them excellent paracrine and autocrine signalling molecules

physiology

• NO mediates a plethora of functions in the body:

1. relaxation of vascular and gostrointestinal smooth muscle
2. inhibition of platelet aggregation
3. reduction of cardiac hypertrophy
4. protection against ischemia/reperfusion damage of the heart
5. improvement in cognitive function

toxicity

• NO is a free radical
• it can react with the superoxide anion to give peroxoynitrate and then hydroxyl radicals, the latter are very reactive and toxic- used in macrophages
• it can also bind to non-haem iron in proteins irreversibly, leading to destrution of the proteins
• many of these are in the mitochondira, leading to cell death

Biosynthesis

• Nitric Oxide Synthase (NOS) enzymes
• catalyse the production of NO from L-arginine

NO synthase isozymes

• neronal NOS 

-nervous system and skeletal system (type II)

- cell communication

• endothelial NOS

- endothelium 

-vasodilation 

• inducible NOS

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