SN4
SHORT NOTE
5M
★ High-yield
Describe the synthesis and actions of the eicosanoids. Explain the action of aspirin.
Definition
Eicosanoids = biologically active 20-carbon compounds derived from arachidonic acid and related fatty acids. They include prostaglandins, thromboxanes, prostacyclin and leukotrienes.
- They act as local hormones (autacoids) — produced on demand, acting near their site of formation, and rapidly destroyed
- They are not stored
Synthesis
Membrane phospholipid → phospholipase A2 — inhibited by corticosteroids → arachidonic acid → Two routes
| Pathway | Enzyme | Products | Inhibited by |
|---|---|---|---|
| Cyclo-oxygenase | COX-1 and COX-2 | Prostaglandins, thromboxane, prostacyclin | Aspirin, NSAIDs |
| Lipoxygenase | 5-lipoxygenase | Leukotrienes | Zileuton; receptors blocked by montelukast |
Chief Actions
| Eicosanoid | Source | Chief actions |
|---|---|---|
| PGE2 | Most tissues | Vasodilatation, pain, fever; protects gastric mucosa; contracts uterus |
| PGF2α | Uterus | Uterine contraction; bronchoconstriction; luteolysis |
| PGI2 (prostacyclin) | Vascular endothelium | Vasodilatation; inhibits platelet aggregation |
| TXA2 (thromboxane) | Platelets | Vasoconstriction; promotes platelet aggregation |
| Leukotrienes (LTC4, D4, E4) | Leucocytes, mast cells | Bronchoconstriction (1000× histamine), ↑ vascular permeability — the slow reacting substance of anaphylaxis |
| LTB4 | Neutrophils | Powerful chemotaxis |
CLINICAL PEARL
Prostacyclin and thromboxane are physiological opposites — the balance between endothelial PGI2 and platelet TXA2 determines whether blood clots on a vessel wall.
WHY Low-dose Aspirin Works
Low-dose aspirin irreversibly acetylates COX → Platelets have NO nucleus → cannot make new COX → Effect lasts the platelet's whole 8–12 day lifespan → Endothelial cells can resynthesise COX and recover → Net result: TXA2 suppressed, PGI2 preserved → antithrombotic
Applied Aspects
- NSAIDs relieve pain, fever and inflammation by blocking COX; the gastric ulceration is caused by loss of protective PGE2, not by local acidity
- Selective COX-2 inhibitors spare the stomach but shift the balance toward thromboxane → increased cardiovascular risk
- Corticosteroids inhibit phospholipase A2 (through lipocortin) → block both pathways — hence more powerful than NSAIDs
- Montelukast blocks leukotriene receptors in asthma
- Therapeutic prostaglandins — misoprostol (ulcer prevention), dinoprostone (labour induction), latanoprost (glaucoma), alprostadil (to keep the ductus arteriosus open)
All questions in Lipid Metabolism
- Q1Describe the β-oxidation of fatty acids. Explain the carnitine shuttle, the energetics for palmitate, and the regulation of the pathway. ★
- Q2Describe the synthesis and utilisation of ketone bodies. Explain the causes of ketosis and the biochemical basis of diabetic ketoacidosis. ★
- Q3Describe the de novo synthesis of fatty acids. Explain the citrate shuttle, the role of acetyl-CoA carboxylase, and compare it with β-oxidation. ★
- Q4Describe the biosynthesis and regulation of cholesterol. Give its functions, transport and fate. Add a note on hypercholesterolaemia. ★
- Q5Classify the plasma lipoproteins. Describe their metabolism and the role of apolipoproteins. Add a note on the hyperlipoproteinaemias. ★
- SN1Describe the carnitine shuttle and its regulation. ★
- SN2Define fatty liver. Describe its causes and mechanisms. Add a note on lipotropic factors. ★
- SN3Define essential fatty acids. Give their sources, functions and the features of deficiency. ★
- SN4Describe the synthesis and actions of the eicosanoids. Explain the action of aspirin. ★
- SN5Describe lipoprotein lipase with its site, activator and significance.
- SN6Classify phospholipids and describe their functions. Add a note on lung surfactant. ★
- SN7Describe the biochemical basis of atherosclerosis and the lipid risk factors. ★