Nitrogen Monoxide

Question 1

Characteristics of Nitrogen Monoxide

Answer 1

• Smallest molecule which has a biological effect
• gaseous
• free radical

Question 2

Biological effects of Nitrogen Monoxide

Answer 2

1) Smooth muscle relaxation
- in GI and blood vessels

2)Neurotransmission

3) Cytotoxic effect
- in tumour and microbes

Question 3

Mechanism of Guanylate Cyclase

Answer 3

GTP —> cGMP + PPi

-requires Mg2+

Question 4

Membrane bound GC

Answer 4

Activated by: - ANF (produced by Atrial myocytes )

Effects:

• Na+ excretion
• Vasodilation
• Inhibit secretion of Aldosterone + Vasopressin

Question 5

Method of Vasodilation by GC activation

Answer 5

ANF receptor -> GC activation in endothelial cell smooth muscle cells -> cGMP dependent protein kinases -> phosphorylation of pm Ca2+ ATPase-> ca decreae -> relaxation

Question 6

Soluble GC

Answer 6

• found in cytosol, with no relation to receptors.
• present in MOST CELLS.
• activated by nitrogen containing compounds such as NO.
• effect on smooth muscle (vascular,tracheal,gi smooth muscle) -> RELAXATION

Question 7

what does cGMP activate which mediates cellular effects?

Answer 7

activates:

• cGMP-dependent portein kinases
• cGMP-regulated phosphodiesterases
• CGMP-regular ion channels

Question 8

Which enzyme synthesises NO

Answer 8

Nitrogen (mono)Oxide Synthase –> [NOS]

Question 9

Steps in NO synthesis

Answer 9

L-arginine —1—> N-Hydroxy-arginine—2—> citrulline

1: O2, 2e-
- H2O

2. O2, 1e-
   
   • H2O
   • NO

Question 10

where is NOS purified and cloned?

Answer 10

• brain
• endothelial cells
• macrophages

Question 11

genetics relating to NOS

Answer 11

• NOS is coded by three genes.
• further isoenzymes are formed by alternative splicing.
• 50-60% homology
• 58% homology with cytochrone P450 (in cerebellum has a Cit P450 activity)