Lipid Mediators

Question 1

What is the structure of arachidonic acid?

Answer 1

20 carbon omega 6 fatty acid with 4 double bonds

Question 2

How is arachidonic acid derived?

Answer 2

From dietary polyunsaturated fatty acids - e.g. converted from linoleum acid via desaturation, elongation and then desaturation

Question 3

How is arachidonic acid stored?

Answer 3

esterified in membrane phospholipids

Question 4

How is arachidonic acid released from membranes?

Answer 4

Enzyme phospholipase A2 metabolises membrane and releases arachidonic acid

Question 5

How is phospholipase A2 activated?

Answer 5

By an increase in intracellular calcium

Question 6

How is arachidonic acid metabolised?

Answer 6

by cyclooxygenase (COX) or by lipoxygenase

Question 7

What is the role of COX-1?

Answer 7

homeostasis - doesn’t require post translational modification

Question 8

What is the role of COX-2?

Answer 8

it is inducible - the gene is induced by inflammatory stimuli such as IL-1 or growth stimuli

Question 9

What are cycloendoperoxides?

Answer 9

The product of metabolism of arachidonic acid by COX

Question 10

Are cycloendoperoxides stable?

Answer 10

No - they are rapidly metabolised into stable prostaglandins by isomerases

Question 11

What does the nomenclature of prostaglandins represent?

Answer 11

The letter denotes the ring structure and the subscript number represents the number of double bonds

Question 12

What are the actions of PGE2?

Answer 12

vasodilations, natriuretic, hyperalgesic, pyrogenic, angiogenic

Question 13

What are the actions of NSAIDs?

Answer 13

Blocks COX - anti-inflammatory, analgesia, antipyretic

Question 14

What are the side effects of NSAIDs?

Answer 14

gastric irritation

Question 15

What is the benefit of the anti-inflammatory action of NSAIDs?

Answer 15

Because prostaglandins are only involved in the vascular component of inflammation and not cellular inflammation, NSAIDs wont modify the course of inflammation and will only give palliative care

Question 16

What is the benefit of using NSAIDs for pain relief?

Answer 16

Prostaglandins on their own don’t cause pain, it is involved in synergy with another analgesic substance, therefore if the cause of the pain is unknown, removing prostaglandin will always stop the pain from being amplified

Question 17

How does prostaglandin cause fever?

Answer 17

Prostaglandin itself doesn’t reach the brain because it would be metabolised in circulation, instead IL-1 released by macrophage activation travels to the hypothalamus where it acts to activate COX and increase prostaglandin at the site which increases cAMP to cause fever

Question 18

How does PGE2 protect against gastric ulceration?

Answer 18

By promoting blood flow, promoting angiogenesis, increasing depth of mucous barrier, reducing gastric acid secretion

Question 19

How do NSAIDs cause gastric ulceration?

Answer 19

By removing action of PGE2

Question 20

What are prostacyclin and thromboxane?

Answer 20

Other products of COX metabolism of arachidonic acid

Question 21

When and where is prostacyclin produces?

Answer 21

All the time by endothelial cells

Question 22

What is the action of prostacyclin?

Answer 22

reduces platelet activation and causes vasodilation

Question 23

Why is prostacyclin important?

Answer 23

Because it protects against coronary artery disease

Question 24

Where is thromboxane produced?

Answer 24

By platelets

Question 25

What are the actions of thromboxane?

Answer 25

Increases platelet activation and causes vasoconstriction - opposite of prostacyclin

Question 26

Why is aspirin used in the treatment of coronary artery disease?

Answer 26

Because it causes COX activity to be lost in platelets for 8 days, whereas it only causes COX activity to be lost in endothelium for a few hours - this means that it tips the ratio of prostacyclin and thromboxane in favour of prostacyclin enhancing its protective effects against coronary artery disease

Question 27

Why is aspirin different from other NSAIDs?

Answer 27

Because it enables increased production of epi-LXA4 and epi-LXB4 which are involved in inflammation resolution

Question 28

What is eicosapentaenoic acid?

Answer 28

fish oil - an omega 3 dietary polyunsaturated fatty acids

Question 29

What is the benefit of eicosapentaenoic acid?

Answer 29

Metabolism results in more prostacylin than thromboxane - this may explain the low incidence of coronary artery disease in cultures that have a rich marine oil diet

Question 30

What are the products of metabolism of arachidonic acid by lipoxygenase?

Answer 30

5-HPETE which makes leukotrienes

Question 31

What is the role of 5-lipoxygenase?

Answer 31

No physiological role - only important in inflammation - which means that it is a good target for intervention

Question 32

How is 5-lipoxygenase activated?

Answer 32

By increased intracellular calcium (from infection, allergy, inflammation)

Question 33

What are the actions of leukotrienes?

Answer 33

bronchoconstriction, leaky vessels

Question 34

What is the action of leukotriene B4?

Answer 34

No direct action on smooth muscle, promotes inflammation by attracting leukocytes

Question 35

Are there any therapeutics to target the leukotriene B4 receptor (BLT)?

Answer 35

No