Flashcards in Signalling via Intracellular Receptors Deck (17)
What is NO made from?
What is the intermediate molecule of making NO from L-arginine?
What is the byproduct of making NO from L-arginine?
What is the enzyme that catalyses L-arginine to NO?
Nitric oxide synthase (NOS)
Describe how NOS catalyses the synthesis of NO?
Through two serial monooxygenase reactions analogous to those of the NADPH-dependent cytochrome PH450 oxidoreductase system
What is cNOS?
Constitutive NOS. Its enzymatic activity is induced by calcium/calmodulin. It is transiently active
What are the two forms of cNOS?
eNOS (endothelial - bound to cell membrane) and nNOS (neural - cytosolic)
Where is eNOS expressed?
Endothelium, cardiac myocytes, renal mesangial cells, osteoblasts, platelets)
Where is nNOS expressed?
CNS, NANC neurons, ENS, retina
What is iNOS?
Inducible NOS, transcription is inducible and it is always active. Pathological stimuli activate their transcription. Main role is in the immune system.
Where is iNOS expressed?
How is NO induced?
1. ACh released from synapse and it activates NO synthase (cNOS) in endothelial cells
2. Activated NOS generates NO from arginine
3. NO binds to guanylyl cyclase, converting GTP to cGMP
4. cGMP activates cGMP-dependent protein kinase (PKG), which converts myosin light chain phosphatase into myosin light chain which causes muscle relaxation
What affect does NO have on vasculature?
Autonomic nerves release ACh which acts on endothelial cells
Endothelial cells release NO which causes surrounding smooth muscle to relax
NO also inhibits platelet aggregation and vascular smooth muscle proliferation
What is the effect of nNOS on the brain?
nNOS is tethered close to NMDA-type glutamate receptors in the CNS so it can respond to the Ca2+ increase near open channels
Glutamate produced by the presynaptic terminal activates glutamate receptors (NMDA) which stimulates the NO pathway
NO travels to the presynaptic terminal and increases the production of glutamate, creating the state of long term potentiation
What is the role of NO in the immune system?
Kills bacteria and parasites and induces programmed cell death
What is the role of iNOS in inflammatory cells?
It uses NO as a cytostatic and cytotoxic agent. It produces higher numbers of NO