Intro To Cell Signalling And Second Messengers

Question 1

Describe the structure of proteins

Answer 1

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.

Question 2

What is a secondary structure of a protein?

Answer 2

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

Question 3

What is the alpha helix

Answer 3

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

Question 4

What are beta sheets

Answer 4

They are proteins with hydrogen bonds that link different linear polypeptide chain’s together.

They can be in parallel strands and anti parallel strands

Question 5

What are the different shapes and protein structures in a lipid bilayer

Answer 5

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

Question 6

What are subunits in terms of protein protein interactions

Answer 6

When a receptor consists of multiple proteins it causes a complex

The subunits make a complex

Question 7

How do drugs typically act in the body

Answer 7

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

Question 8

What are the four common drug targets of proteins

Answer 8

Receptors
Enzymes
Transporters
Ion channels

Question 9

What are receptors

Answer 9

They are recognition molecules for chemical mediators

Question 10

How do we classify receptors

Answer 10

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

Question 11

What are the four super families of receptors

Answer 11

Ligand gated ion channels ,fastest
G protein coupled receptors
Kinase linked receptors
Nuclear receptors ,slowest

Question 12

What are the four different types of cell signalling

Answer 12

Endocrine , long range via blood stream
Paracrine , local
Neuronal , local via synapses
Contact dependent ,close contact via contact dependency

Question 13

Describe contact dependent cell signalling

Answer 13

Protein to protein interactions between 2 cells , interaction sends signal to both cells , tunnel connecting to cells allowing sharing

Question 14

What is the job of cell surface receptors

Answer 14

They send the signal into the intracellular environment to inform the cell of the correct response

Question 15

What is transduction

Answer 15

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.

Question 16

What is a second messenger

Answer 16

It is an intercellular signalling molecule

Question 17

What are some typical second messenger molecules

Answer 17

cAMP ,cGMP , cADPR
IP3 ,DAG,PIP3
ca2+
Nitric oxide

Question 18

Describe the process of amplification and it’s importance

Answer 18

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.

Question 19

Describe the process of cAMP second messenger

Answer 19

1. 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
2. This activates the effector protein Adenylyl Cyclase (membrane bound) (this
3. AC catalyses the reaction that converts ATP into cAMP
4. 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)
5. Protein kinase A is made up of two regulatory subunits, the regulatory subunits dissociate leaving the catalytic subunits free and active
6. 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

Question 20

What are some of the proteins that can be regulated by protein kinase A

Answer 20

Fatty acid formation
Glycogen formation
DNA syntheses
Microtubules assembly or disassembly
Protein synthesis

Question 21

What are the main type of phosphoglycerides on cell membranes.

Answer 21

Phosphatidyl
Ethanolamine
Serine
Choline
Sphingmyelin
Sphingosine

Question 22

What are the three phosphatidyl inositol types found in the inner leaflet of the plasma membrane

Answer 22

PI phospatidyl linositol
PiPphosphate
PIP 2 bisphosphate

Question 23

What is the function of the pi kinases

Answer 23

These kinases phosphorylate the free carbons on the inositol rings (4 , 5)

Question 24

What is the function of the pip kinase

Answer 24

To add another phosphate group to the phosphatidyl ring making pip2

Question 25

What is the function of pi3 kinase

Answer 25

It can phosphorylate all three phospholipids , by adding a phosphate group to carbon 3
Pi3 phosphate
Pi3,4 bisphosphate
Pi3,4,5 triphosphate

Question 26

Why’s is pip3 important

Answer 26

When it’s at the plasma membrane it acts as docking site for proteins that contain a PH domain e.g. sos

Question 27

Q1, describe how cAMP is generated and how it is inactivated

Answer 27

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

Question 28

Q2, Describe the process of phosphorylation and why it is important in cell signalling

Answer 28

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.

Question 29

Q3 what are the two different enzymes that can act on phosphatidylinositol 4,5 bisphosphate and how do they create the second messengers

Answer 29

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.