Intro To Cell Signalling And Second Messengers Flashcards
Describe the structure of proteins
All proteins are made up of amino acids join together into a polypeptide chain.
A protein is made up of a polypeptide backbone and side chains.
What is a secondary structure of a protein?
It is when the protein folds up on itself in different shapes due to the interaction between the amino acids in the chain , it seems to take the shape of the lowest energy state as it is more favourable
What is the alpha helix
They are hydrophobic regions of the protein which are often embedded in the lipid bilayer. The patterns are held together by hydrogen bonds.
Between amino acids on the same chain
What are beta sheets
They are proteins with hydrogen bonds that link different linear polypeptide chain’s together.
They can be in parallel strands and anti parallel strands
What are the different shapes and protein structures in a lipid bilayer
Single alph helix
Multiple alpha helix
Rolled beta sheet
Anchored may a an alpha helix
Lipid chain attachments (inner or outer)
GPI anchored
Association (transient or permanent) in both in or out
What are subunits in terms of protein protein interactions
When a receptor consists of multiple proteins it causes a complex
The subunits make a complex
How do drugs typically act in the body
They act by influencing proteins on cells or inside cells and changing the way these proteins behave (also called the pharmacological effect) protein becomes drug target
What are the four common drug targets of proteins
Receptors
Enzymes
Transporters
Ion channels
What are receptors
They are recognition molecules for chemical mediators
How do we classify receptors
By it’s ligands
By it’s sequence similarity to other receptors
By drugs that act on it (pharmacology)
By it’s associated signalling pathway
By protein structure
What are the four super families of receptors
Ligand gated ion channels ,fastest
G protein coupled receptors
Kinase linked receptors
Nuclear receptors ,slowest
What are the four different types of cell signalling
Endocrine , long range via blood stream
Paracrine , local
Neuronal , local via synapses
Contact dependent ,close contact via contact dependency
Describe contact dependent cell signalling
Protein to protein interactions between 2 cells , interaction sends signal to both cells , tunnel connecting to cells allowing sharing
What is the job of cell surface receptors
They send the signal into the intracellular environment to inform the cell of the correct response
What is transduction
The relaying of the message that’s come from the reception of a molecule that was picked up by a cell surface receptor , to the target protein.
What is a second messenger
It is an intercellular signalling molecule
What are some typical second messenger molecules
cAMP ,cGMP , cADPR
IP3 ,DAG,PIP3
ca2+
Nitric oxide
Describe the process of amplification and it’s importance
Amplification can generate many molecules of a second messenger which allows a greater number of kinases to be activated, these in turn phosphorelate and activate other proteins, and each stage causes ten fold or 100 fold signal amplification, the strength of the signal is increased.
Describe the process of cAMP second messenger
- The G protein coupled receptor activates when binds with a ligand, which causes dissociation into g alpha gamma and g alpha , g alpha moves then associates with the effector protein AC
- This activates the effector protein Adenylyl Cyclase (membrane bound) (this
- AC catalyses the reaction that converts ATP into cAMP
- cAMP is a diffusible water soluble (diffuses into cytoplasm) second messenger that moves away from the plasma membrane to engage with and activate protein kinase A ( requires 4 camps)
- Protein kinase A is made up of two regulatory subunits, the regulatory subunits dissociate leaving the catalytic subunits free and active
- Active protein kinase A can then activate many other proteins in the cell by phosphorylation.
7, phosphorylase causes glycogen breakdown , or creb which also gets phosphorylated which means it can regulate genes
What are some of the proteins that can be regulated by protein kinase A
Fatty acid formation
Glycogen formation
DNA syntheses
Microtubules assembly or disassembly
Protein synthesis
What are the main type of phosphoglycerides on cell membranes.
Phosphatidyl
Ethanolamine
Serine
Choline
Sphingmyelin
Sphingosine
What are the three phosphatidyl inositol types found in the inner leaflet of the plasma membrane
PI phospatidyl linositol
PiPphosphate
PIP 2 bisphosphate
What is the function of the pi kinases
These kinases phosphorylate the free carbons on the inositol rings (4 , 5)
What is the function of the pip kinase
To add another phosphate group to the phosphatidyl ring making pip2
What is the function of pi3 kinase
It can phosphorylate all three phospholipids , by adding a phosphate group to carbon 3
Pi3 phosphate
Pi3,4 bisphosphate
Pi3,4,5 triphosphate
Why’s is pip3 important
When it’s at the plasma membrane it acts as docking site for proteins that contain a PH domain e.g. sos
Q1, describe how cAMP is generated and how it is inactivated
When a G coupled receptor protein binds with a ligand it causes dissociation into g alpha gamma and g alpha. The g alpha subunit then move to the cell membrane protein effector called adenlyl cyclase. This effector catalysed the reaction that converts ATP into cAMP
To inactivate cAMP the cell degrades it using phosphodiesterase enzyme which metabolises cAMP into 5-AMP
Q2, Describe the process of phosphorylation and why it is important in cell signalling
Phosphorylation is the transfer of a phosphate group to a protein or lipid. It is a reversible modification. This is catalysed by either a lipid kinase or a protein kinase. I’m proteins only 3 amino acid residues can be phosphorylated, serine ,threonine, and tyrosine. The kinase uses ATP and transfers the terminal phosphate group onto the hydroxyl residue of the amino acid
Phosphorylation is important as it is a way of transferring a message along a signalling pathway. Addition of a phosphate group typically activates a target protein. The action can be inactivated with the use of the phosphatase enzyme which removes the phosphate group, this means it is an efficient way to rapidly transfer a signal.
Q3 what are the two different enzymes that can act on phosphatidylinositol 4,5 bisphosphate and how do they create the second messengers
The enzyme phospholipase c (PLC) acts on PIP2 in order to generate the second messengers IP3 which is water soluble therefore moves into the cytoplasm this second messenger acts on the receptor of the ER membrane to release ca2+ from the store into the cytoplasm.The breaking down of PiP2 also generates the second messengers DAG which stay on the cell membrane. DAG is able to diffuse into the cell membrane to activate different proteins. DAG acts on the activation of protein kinase C. PKC activation also requires ca2+ signal. DAG can be cleaved to generate arachidonic acid.PLC cleaves PIP2. Another enzyme acting on PiP2 is phospholipase 3 kinase (p13k). This enzyme adds a phosphate group to the 3rd carbon of the inositol ring turning it into PIP3 (3,4,5). PIP3 is a second messenger.
