Eicosanoids

Question 1

Eicosanoid synthesis initiated by:

Answer 1

• Epinepherine & other hormones
• Thrombin & other proteases
• Histamine produced by mast cells
• Tissue injury/inflammation, ex. MI

Question 2

Eicosanoid synthesis pathway

Answer 2

• PLA2 releases arachidonic acid (precursor of eicosanoids)
  
  • Inhibited by cortisol
• Tissue injury and inflammation triggers eicosanoic acids release from plasma membrane
• Arachidonic acid can become:

1. Leukotrienes via LOX pathway
2. Prostaglandins via COX pathway

• PGH2 can then converted to:
  
  • PGI2 (Prostacyclin) via Prostacyclin Synthase
  • PGD, PGE, PGF via Reductase or Isomerases
  • Thromboxane via Thromboxane Synthetase

Question 3

Prostaglandins

Answer 3

• PGE2
  
  • has 2 double bonds
  • Vasodilation
  • produced by most tissues
  • synthesized in kidney & involved in reduction of ADH-induced water reabsorption
  • produced in large amounts by monocytes & macrophages & neutrophils (fever & rubor)
  • known as Dinoprostone as abortifacient
• PGI2
  
  • has a single double bond
  • Vasodilation
  • Inhibits Platelet aggregation
  • produced by endothelium of blood vessels
• PGF2alpha
  
  • Vasoconstriction
  • Contracts smooth muscle (uterus)
  • Bronchoconstriction
  • produced by most tissues
  • produced in large amounts by monocytes & macrophages

Question 4

Prostaglandin endoperoxide activity

Answer 4

• 2 distinct activities:

1. COX activity
2. Gluthathione-dependent hydroperoxidase activity

*

Question 5

Thromboxane (TXA2) synthesis & fx

Answer 5

• TXA synthase converts PGH2 to TXA2
• produced by platelets
• stimulates platelet aggregation
• causes vasoconstriction