Lipids and Cell Membranes 2

Question 1

How do lipids participate in cell-cell communication mechanisms?

Answer 1

By giving rise to intracellular second messengers.

They also act as precursers for eicosanoids

Question 2

What are the 6 steps in cell to cell communication?

Answer 2

1. Synthesis of signal
2. Release of signalling molecule (exocytosis/diffusion/cell to cell contact)
3. Transport of signal to target cell
4. Detection of signal by specific receptor protein
5. A change in cellular metabolism, function or development triggered by receptor-signal complex
6. Removal of signal or desensitisation

Question 3

Give two examples of long-range signals and how they work

Answer 3

Endocrine - hormones released by endocrine cells and carried in blood stream to target cells
Neurotransmitters (long distances because neurons can be very long)

Question 4

Give two examples of short range signals and how they work

Answer 4

Paracrine - Signalling molecules only affecting target cells in close proximity
Autocrine - Cells respond to substances that they themselves release

Question 5

Give an example of how multiple types signalling can be occurring simultaneously

Answer 5

Insulin releases can act in an autocrine, paracrine and endocrine manner.

Question 6

Where can signalling molecules bind? What is most common?

Answer 6

Extracellular receptors - This is most common

Intracellular receptors- Less common and occurs with hydrophobic molecules

Question 7

What are the different types of receptors? and their time scale

Answer 7

Ligand gated ion channels - milliseconds
G-protein-coupled receptors - seconds
Kinase-linked receptors - hours
Nuclear receptors - hours (longer because it involved time for proteins to be made)

Question 8

Using cortisol as a specific example, explain how intracellular signalling occurs

Answer 8

Cortisol binds to intracellular receptor in cytosol changing its conformation. The activated receptor then translocated into the nucleus where is binds to a regulatory region of the target gene and activates transcription.

Question 9

What is PIP(2)? (small two) and what is it a substrate for?

Answer 9

A phospholipid found in the lipid bilayer called Phosphotidylinositol 4,5-bisphophate. It is a substrate for the enzyme phospholipase C (PLC)

Question 10

What is the function of Phospholipase C? (PLC)

Answer 10

It cleaves PIP(2) into two products; Inositol 1,4,5 triphosphate (IP(3)) and Diacyglycerol (DAG)

Question 11

How is Protein Kinase C (PKC) activated?

Answer 11

PIP(2) is cleaved into IP(3) and DAG by PLC. The IP(3) opens calcium channels in the endoplasmic reticulum which binds to domain C2 causing it to trans-locate to the cell membrane where DAG binds to the C1 domain causing a conformational change and activating the enzyme.

Question 12

With IP(3) release, what happens to calcium levels?

Answer 12

They greatly increase and since calcium is used to regulate protein function this is very important

Question 13

What are some substrates for PKC (Protein Kinase C)

Answer 13

Tumour suppressor p53 - prevents tumor formation.
Ca(v) 1.2 - heart muscle contraction.
Cytokine - activates B cells

Question 14

After signal transduction, what occurs to IP(3)

Answer 14

it is recycled and returned to the membrane as PIP(2)

Question 15

What are Eicosanoids and what are some of their features?

Answer 15

• They are inflammatory mediatiors

- Considered local hormones as they act on cells close to their site of formation, as they are rapidly degraded.

Question 16

What are the principle Eicosanoids?

Answer 16

Prostoglandins, thromboxanes and leukotrienes

Question 17

What is the initial and rate-limiting step in eicosanoid formation?

Answer 17

The liberation of arachidonic acid from phospholipids by phospholipase A2 (PLA(2))

Question 18

Where does Phospholipase A2 (PLA(2))cleave the fatty acid?

Answer 18

On the second chain of a fatty acid

Question 19

What is PLA(2) activated by?

Answer 19

Seratonin receptors, glutamate receptor 1, some cytokine receptors and increase in calcium concentrations.

Question 20

Describe what products form from the breakdown of phospholipids by Phospholipase A2 (PLA(2))

Answer 20

Platelet activating factor (PAF) and arachidonic acid

Question 21

Arachidonic acid can be metabolised by what?

Answer 21

1. Cyclo-oxygenase and peroxidase to form prostaglandins and thromboxanes
2. Lipoxygenase to give leukotrienes

Question 22

What are prostaglandins involved in?

Answer 22

Vasoconstriction/dilation

Inhibit/promote platelet aggregation (depends on receptors), Inflammatory response, thermoregulation and pain.

Question 23

Where are prostoglandins synthesised?

Answer 23

In all tissue and cell types

Question 24

Where are thromboxanes synthesised in?

Answer 24

Platelets

Question 25

What is thromboxanes involved in?

Answer 25

Platelet aggregation and vasoconstriction

Question 26

Where are leukotrienes synthesised?

Answer 26

White blood cells

Question 27

What are leukotrienes involved in?

Answer 27

The immue response and are heavily involved in asthma and allergies. Have amino acid cysteine which is linked to anaphylactic shock

Question 28

What is platelet activating factor involved in? and what is it produced by?

Answer 28

Produced by injured tissue and leukocytes. It is involved in;
Platelet aggregation, vasoconstriction, inflammation and immune response

Question 29

What do non-steroidal anti-inflammatory drugs inhibit? and name exampls of the drugs

Answer 29

They inhibit cyco-oxygenase which in turn inhibits formation of prostaglandins involved in fever, pain and inflammation and also inhibit blood clotting by blocking thromboxane formation in blood platelets. Examples of NSAID’s are aspirin and ibuprofen

Question 30

Explain how aspirin inhibits formation of prostaglandins

Answer 30

It acetylates with a serine hydroxyl group near active site preventing arachidonic acid from binding. This is irreversible but formation of more cyclooxygenases would restore their activity.

Question 31

Explain how aspirin acts as an anticoagulant

Answer 31

It inhibits thromboxane formations via cyclo-oxygenase inhibition in blood platelets. The effect is long lived as platelets lack a nucleus so do not make new enzymes.