12 - Generation of Lipid Derived Hormones

Question 1

Role of phospholipase A2 (PLA2)

Answer 1

*PLA2 has a major role in signal transduction as it releases arachidonic acid (AA C20H32O2), which serves as a precursor to the biosynthesis of prostaglandins, thromboxanes, leukotrienes, and other eicosanoids

Question 2

How is arachidonic acid synthesised?

Answer 2

AA is synthesised in cells from linoleic acid, an essential fatty acid
o We can synthesis AA de novo, we need to eat linoleic acid

Question 3

Pathway to arachidonic acid

Answer 3

Linoleic acid –> gamma linoleic acid –> dihomo gamma linoleic acid –> arachidonic acid

Question 4

What needs to happen before AA can be converted into signalling molecules?

Answer 4

AA must be released from the plasma membrane before it can be converted into signalling molecules and this is the rate limiting step

Question 5

What allows the release of AA?

Answer 5

o There are a number of cell surface receptors that allow the release of AA, this includes g protein coupled receptors, tyrosine kinase coupled receptors and ion coupled receptors
- these activate the ERK MAP kinase cascade
- this phosphorylated and activates phospholipase A2 which then acts of the glycerol phospholipids and cleaves them to release AA

Question 6

What are the two major AA pathways?

Answer 6

The cyclooxygenase pathway and the lipoxygenase pathway

Question 7

What does the cyclooxyrgenase pathway involve?

Answer 7

The C pathway involves enzymes: COX1 and COX2
* Produces prostaglandins, thromboxane, and prostacyclin
* The intermediator is prostaglandin H2

Question 8

What does the lipoxygenase pathway involve?

Answer 8

The L pathway involves the enzyme 5-LO
* Intermediatory is leukotrieneA4 which is then converted into leukotrienes

Question 9

What does phospholipase A2 release?

Answer 9

Phospholipase A2 also releases lysophosphatidylcholine which is converted into platelet activating factor (involved in blood clotting cascade)

Question 10

What are leukotrienes produced by and involved in?

Answer 10

Leukotrienes are produced by cells of the immune system and are involved in asthmatic and allergic reactions by sustaining inflammatory reactions

Question 11

Where are the enzymes that covert AA into leukotrienes?

Answer 11

The immune system cells have the enzymes that can convert AA into leukotrienes

Question 12

What is asthma involved in?

Answer 12

Asthma is involved in the constriction of the lungs- the bronchi is constricted due to smooth muscle action

Question 13

What do leukotrienes affect?

Answer 13

Leukotrienes have a powerful effect on vasoconstriction and bronchoconstriction, they also increase vascular permeability
o Vascular permeability is when the lining of the blood vessels open up to allow immune cells to access
o Bronchoconstriction is undesirable

Question 14

What is used to treat asthma?

Answer 14

Several leukotriene receptor antagonists are used to treat asthma (act on GCPRs)
o Block the action of leukotrienes and prevent bronchoconstriction borugh about by leukrotrienes

Question 15

Give some examples of leukotrienes

Answer 15

Examples of leukotrienes are LTA4, LTB4, LTC4, LTD4, LTE4, and LTF4

Question 16

What is the function of prostaglandins?

Answer 16

Prostaglandins exert only a paracrine (locally active) or autocrine (acting on the same cell form which it is synthesised) function

Question 17

Effectiveness of prostaglandins

Answer 17

They are potent but have short half life before being activated and excreted
o Quite unstable, activated quickly then excreted

Question 18

How many known prostaglandins are there?

Answer 18

There are currently nine known prostaglandin receptors on various cell types

Question 19

What do prostaglandins act on?

Answer 19

Prostaglandins act on a subfamily of cell surface seven-transmembrane receptors. G-protein coupled receptors (GPCRs)
o GPCRs. Elevate cyclic AMP in target cells
Prostaglandins act on a variety of cells, including platelets, endothelium, uterine and mast cells, and have a wide variety of actions

Question 20

Give examples of actions of prostaglandins

Answer 20

o Dilation in vascular smooth muscle cells (lower blood pressure)
o Platelet aggregation
o Sensitise spinal neurons to pain
o Constrict smooth muscle (e.g. uterine)
- Used for delayed labour as a gel
o Regulate inflammatory mediation
o Regulate calcium movement
o Regulate hormone action
o Control cell growth

Question 21

What are thromboxanes?

Answer 21

Thromboxanes are vasoconstrictors and potent hypertensive agents

Question 22

What is thromboxane A2 produced by?

Answer 22

Thromboxane A2 (TXA2) is produced by activated platelets and facilitates platelet aggregation
o Thromboxanes are produced at the wound site causing platelet to clot and causes vasoconstriction limiting bleeding

Question 23

What does aspirin do?

Answer 23

Aspirin inhibits cyclooxygenase (COX) enzyme preventing synthesis of thromboxane within platelets
o Aspirin covalently modifies the COX enzyme

Question 24

What does aspirin act as?

Answer 24

• Aspirin can therefore act as an anti-hypertensive because it can relieve vasoconstriction and prevents thrombosis
• Aspirin acts as a painkiller and an anti-hypertensive (2 role)

Question 25

Physiological stimulus of PLA2

Answer 25

Physiological stimulus: COX1 is generally involved in normal physiological processes (basal level), involved in homeostasis
o Acts on AA to produce thromboxane (platelet aggregation, vasoconstriction), PGI2 (vasodilation, GI mucosal protection) and PGE1/2 (kidney, GI tract, CNS)

Question 26

Inflammatory stimulus of PLA2

Answer 26

Inflammatory Stimulus: COX 2 acts more on AA, conversion of AA into prostalgadin E2 at the site of wounding or infection, causes pain sensitisation and vasodiliation and other inflammatory responses to allow immune cells into the site of inflammation

Question 27

What does paracetamol act on?

Answer 27

Paracetamol is a good anti-inflammatory and pain killer, it blocks the action of COX2, therefore reducing pain and inflammation as it blocks the production of PGE2

Question 28

What does aspirin act on?

Answer 28

Aspirin acts on COX1 and COX2, anti inflammatory and anti-thromboxin