Signalling Flashcards
What is signal transduction
Getting the signal from the outside of the cell to the inside of the cell.
Why can some signalling molecules cross the membrane alone and what are some examples
What are their receptors
They are hydrophobic due to many carbon rings or very small.
Nitric oxide and retinoic acid.
They are the nuclear receptor super family. For steroids and hormones and vitamin D.
What is the structure of NO and what is it’s half life.
How do cells make NO and what enzyme is used
Only has two atoms N and O.
It is a free radical so is highly reactive and has an unpaired electron in its outer shell.
5-10 second half life.
Cells start with the amino acid L Argenine and through two successive oxidations it causes the release of NO from the amino acid.
The enzyme used is nitric oxide synthase.
PICTURE
What is cNOS
What are they regulated by and what is their activity like
What are the two members and what do they do
Constitutive NOS. it is always expressed so is always being transcribed and made.
Regulated by Ca and calmodulin. When they are active their activity is short lived and they make small amounts picomolar NO.
Endothelial NOS -
Bound to the cell membrane. It is expressed in endothelium, cardiac myocytes, renal mesangial cells, osteoblasts and platelets.
Neural NOS-
Expressed in the CNS, NANC neurons, ENS and Retina. It is in the cytosol and not membrane bound.
What is iNOS
when is it expressed and how is it regulated.
What is it’s activity like
Where are they expressed
Inducible NOS, it’s expression is inducible and is not always being transcribed like cNOS.
The transcription is induced by pathological stimuli.
The activity is not regulated at all and it is always turned on.
It makes nanomoles of NO which is more than cNOS and iNOS has a longer lived affect.
They are expressed in macrophages, kupferr cells, neutrophils, fibroblasts, vascular smooth muscle and endothelial cells.
What two things does NO do in blood vessels and how does it do them.
A nerve will release ach which will act on eNOS in endothelial cells and cause them to release NO which causes surrounding smooth muscle to relax.
NO will inhibit platelet aggregation and vascular smooth muscle proliferation so it is an anti atherosclerotic
How will NO relax muscle
NO binds to guanylyl Cyclase enzyme in the smooth muscle cell.
This produces cGMP which will relax the smooth muscle.
This is because it will bind to cGMP dependant protein kinase and activate it.
This will act on MLCphosphatase which will act on MLC and cause relaxation.
How does nNOS work and what can it cause
It is tethered close to the NMDA glutamate receptors so that it can respond to the Ca released when the glutamate receptors bind to glutamate.
nNOS will be activated by Ca and will release NO. The NO will diffuse back to the presynaptic terminal where it will activate glutamate production.
This is a positive feedback loop and helps with long term potentiation.
What does NO do for the immune system
Why is so much NO needed
What happens when NO is over produced
NO is released by iNOS and kills bacteria and parasites and causes programmed cell death.
iNOS needs to make lots of NO because high levels are needed to trigger cell death.
When there is too much NO it can cause inflammatory diseases like asthma. It also plays a role in tumour apoptosis and necrosis.
What does nitroglycerine do
Making dynamite and medicines for heart conditions.
When it enters the body it rapidly breaks down and makes NO.
It can treat angina by relaxing vessels.
What does phosphodiesterase S do
What does viagra do to this
It does the opposite of NO. It will decrease the amount of cGMP.
Viagra inhibits phosphodiesterase S so there is less loss of cGMP and the blood vessels can relax and lead to more blood flow.
What is the structure of nuclear receptors
Typical topology 1 shape.
They have a transcription activating domain and a DNA binding domain and a regulatory domain.
They can bind to inhibitory proteins that inactivate the receptor.
What happens after a ligand binds to a nuclear receptor.
The complex goes and binds to a section of DNA called a DNA response element.
They can either bind as heterodimers or homodimers.
How do glucocorticoid receptors and estrogen receptors bind
Vitamin D, thyroid and retinoic acid
They bind as homodimers to an inverted repeat DNA site. A palindromic sequence.
One receptor from the dimer binds to one sequence and the other binds to the repeat of the sequence on the opposite strand. Both the receptors are the same type.
They bind as heterodimers. One receptor will bind next to a different type of receptor, usually retinoic acid. Two different receptors bind to repeated sequences on the same strand of DNA.
Where are the homodimeric and heterodimeric receptors found when they are active and inactive
Homo-
Found in the cytoplasm when no ligand is bound. And when a ligand binds they move to the nucleus.
They are anchored in the cytoplasm by inhibitor proteins such as hsp90.
Hetero-
They are always found in the nucleus.
Without a ligand they act as repressors by recruitment of histone deacetylases.
With a ligand they recruit histone acetylases which activate the DNA.
