13- The Eicosanoids

Question 0

What enzyme cleaves the fatty acid off the starting material? What kinds of compounds activate this enzyme? What inhibits it?

Answer 0

phospholipase A_2

Activators: stimuli such as Angiotensin, Bradykinin, Epinephrine, and Thrombin

Inhibitors: anti-inflammatory corticosteroids like Lipcortin

Question 1

What type of compounds supply the precursors for eicosanoids? Where are they found?

Answer 1

Glycerophospholipids provide the major source for eicosanoid precursors. Found in the plasma membrane

Question 2

What are the general types of eicosanoids, and how did their names arise?

Answer 2

1) Prostaglandins (originally thought to have come from only the prostate gland)
2) Leukotrienes (first found in leukocytes and discovered to be the slow reacting substance of anaphylaxis)
3) Thromboxanes (originally found in thrombocytes, i.e. platelets)

Question 3

What enzymes paths are used in the biosynthesis of prostaglandins, Thromboxanes, leukotrienes?

Answer 3

First use phospholipase A_2 to form arachidonate.

Then, for prostaglandin or thromboxane, use Cyclooxgenase.

For Leukotriene, use a lipoxygenase

Question 4

What compounds inhibit cyclooxgenases?

Answer 4

Aspirin and Non-steroidal anti-inflammatory drugs (NSAIDs).

Question 5

What are some of the effects that prostaglandins can have?

Answer 5

1) Stimulate smooth muscle contraction
2) regulate steroid synthesis
3) Inhibit gastric secretion
4) Inhibit hormone sensitive lipases
5) Inhibit platelet aggregation
6) Regulate nerve transmission
7) Sensitize to pain
8) Mediate inflammatory response

Question 6

Where are leukotrines found?

Answer 6

Leukocytes, mast cells, vascular tissue, platelets and macrophages

Question 7

What path is used to synthesize them?

Answer 7

Synthesized from arachidonate or linolenate using the lipoxygenase path.

Question 8

What are the slow reacting substances of anaphylaxis?

Answer 8

The “slow reacting substances of anaphylaxis” (SRS-A) are compounds of the lipoxygenase pathway.

Leukotriene-C4
Leukotriene-D4
??What is the third?

Question 9

What biological effects do leukotrienes have?

Answer 9

1) Contraction of smooth muscle in the pulmonary airway

2) Alteration in permeability of microvasculature, resulting in fluid and protein leaking into the tissue

Question 10

How are leukotrienes degraded?

Answer 10

They can be made inactivate via a myeloperoxidase reaction to yield leukotriene B4