Eicosanoids

Question 1

What are the FOUR subfamilies of Eicosanoids?

Answer 1

1. Prostaglandins
2. Prostacyclin
3. Thromboxanes
4. Leukotrienes

Question 2

What is the structure of Eicosanoids?

Answer 2

20-carbon fatty acid derivative

Question 3

What are Eicosanoids synthesised from?

Answer 3

• Polyunsaturated fatty acids
• Particularly Arachidonic Acid

Question 4

What is the structure of Arachidonic Acid?

Answer 4

20 C:4 unsaturated bond structure

Question 5

Are Eicosanoids soluble in water?

Answer 5

No.
Poorly soluble in water

Question 6

What are the functions of Eicosanoids?

Answer 6

Act as autocrine or paracrine local mediators

Question 7

Where do Eicosanoids bind to receptors?

Answer 7

Cell surface

Question 8

What receptors do Eicosanoids bind and how does signalling occur?

Answer 8

7-TM receptors and signalling occurs via heterotrimeric G-proteins (GCPRs)

Question 9

What biological functions are Eicosanoids involved in?

Answer 9

• Inflammation
• Pain sensation
• Platelet aggregation
• Asthma

Question 10

Are Eicosanoids stored or produced on demand?

Answer 10

Produced on demand

Question 11

When are Eicosanoids synthesised?

Answer 11

When a cell is activated by mechanical trauma, growth factors, cytokines, or other stimuli

Question 12

How is the rate of release of Eicosanoids determined?

Answer 12

Mainly by rate of synthesis, which is dependent on availability of precursor (arachidonic acid)

Question 13

What type of fatty acid is Arachidonic Acid?

Answer 13

• Essential fatty acid
• Cannot be synthesised from scratch

Question 14

Where is Arachidonic Acid normally present?

Answer 14

In cells that are esterified at the 2-position in phospholipids

Question 15

How is Arachidonic Acid released from phospholipids?

Answer 15

By the action of phospholipase A2 (PLA2) enzymes

Question 16

What is the mechanism of action in the production of Eicosanoids from Arachidonic Acid?

Answer 16

1. Arachidonic Acid released at ER and nuclear membranes by PLA2 and presented to prostaglandin H synthase (PGHS / COX)
2. PGHS / COX converts arachidonic acid to prostaglandin H2 (PGH2)
3. Enzymatically catalysed reduction or isomerisation of PGH2 generates eicosanoids

Question 17

How is PLA2 regulated?

Answer 17

Phosphorylation and an influx of Ca2+ which triggers PLA2 activation and translocation to the nuclear membrane

Question 18

Which amino acid does phosphorylation of PLA2 occur on?

Answer 18

Serine-505

Question 19

What causes the phosphorylation of PLA2?

Answer 19

Result of ligand binding to receptors such as the interferon receptors, mGLUR1, etc

Question 20

What inhibits PLA2 and reduces inflammation?

Answer 20

Glucocorticoids stimulate the release of lipoprotein

Question 21

How is Arachidonic Acid generated?

Answer 21

• By the action of Phospholipase C (PLC) on phospholipids to form DAG
• Cleaved by DAG lipase to form Arachidonic Acid and monoacylglycerol

Question 22

What are the TWO isoforms of Prostaglandin H synthase?

Answer 22

1. COX-1
2. COX-2

Question 23

What is the function of COX-1?

Answer 23

Responsible for basal prostaglandin synthesis

Question 24

What is the function of COX-2?

Answer 24

Important for induced prostaglandin synthesis (inflammatory response)

Question 25

What major group of anti-inflammatory drugs target Eicosanoid biosynthesis?

Answer 25

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

Question 26

What do NSAIDs target in Eiscosanoid biosynthesis?

Answer 26

COX-1 and COX-2

Question 26

Which isoform of Prostaglandin H synthase is the target preference for NSAIDs in Eicosanoid biosynthesis?

Answer 26

COX-2

Question 27

Which classical NSAIDs inhibit COX-1 and COX-2?

Answer 27

Aspirin and Ibuprofen

Question 28

What causes the anti-coagulant properties of Aspirin?

Answer 28

Inhibits the formation of Thromboxane A2 * released by platelets and causes aggregation

Question 29

TRUE OR FALSE: Eicosanoids often act in agonist pairs

Answer 29

False. Act in ANTAGONIST pairs

Question 30

How are Leukotrienes synthesised?

Answer 30

By Lipo-Oxygenases

Question 31

How are Leukotrienes modified?

Answer 31

Conjugation to more polar molecules such as **Glutathione (Leukotriene C4)** or **Cysteinylglycine (Leukotriene D4)**

Question 32

How do Leukotrienes affect airway smooth muscle?

Answer 32

Cause contraction (LTD4)

Question 33

What are TWO examples of lipophilic hormones that bind cell surface receptors?

Answer 33

1. Platelet Activating Factor (PAF) 2. Lysophosphatidic Acid (LPA)

Question 34

What effect does Lysophosphatidic Acid (LPA) have on target cells?

Answer 34

* Stimulation of growth * Cell division * Transformation * Alteration of cell morphology