test 7 eicosanoids

Question 1

eicosanoids

Answer 1

o produced from arachidonic acid, a 20 carbon polyunsaturated fatty acid
o They are produced in all tissues and are typically called “local hormones”. They act on their cell of origin (autocrine) and target neighboring cells (paracrine).
o They are rapidly degraded, hence have a short half-life, and are not transported into the periphery by the bloodstream.
o Highly potent and display a wide spectrum of biological activity.

Question 2

Biological activity of eicosanoids

Answer 2

o Fever
o Inflammatory response
o Hypersensitivity reactions
o Immune system modulation
o Regulation of blood pressure
o Smooth muscle function
o Gastric integrity
o Renal function
o Clotting
o Reproductive function
o Tissue growth
o Regulation of the sleep/wake cycle
o Pain signals

Question 3

synthesis of eicosanoids from dietary linoleic acids

Answer 3

• Dietary linoleic acids (C18, from plant oils)

- elongase and desaturase for arachidonic acid (C20)

Question 4

Synthesis of eicosanoids from eicosapentaenoic acids

Answer 4

• Eicosapentaenoic acids (C20, from fish oils) -> eicosanoids

Question 5

Synthesis of eicosanoids

Answer 5

o AA must first be released from the plasma membrane for eicosanoid synthesis to occur. AA is released from the phospholipids by the action of phospholipases (PLA2 or C) in response to signals.
- PLA2 is stimulated by epinephrine, bradykinin, angiotensin-II, thrombin, membrane injury
o Following mobilization, AA is oxygenated by separate pathways, major ones being the cyclooxygenase and lipoxygenase pathways, leading to the synthesis of prostaglandins, leukotrienes, and thromboxanes.

Question 6

cyclooxygenase (COX) enzymes convert AA into

Answer 6

• prostaglandins

- COX-1 and COX-2 enzymes

Question 7

COX-1

Answer 7

o Regulates normal cellular functions.
o COX-1 is constitutively expressed at low levels.
o COX-1 is required for maintenance of gastric tissue, renal homeostasis, and platelet aggregation.

Question 8

COX-2

Answer 8

o Increases prostanoids that occurs with disease, cancer, and inflammation, and in response to mediators such as TNF-α and IL-1.
o COX-2 is inducible, which means that its expression varies depending on the stimulus

Question 9

Lipoxygenase enzymes convert AA into

Answer 9

• leukotrienes

Question 10

Lipoxygenase pathway

Answer 10

o AA is converted to 5-HPETE (hydroperoxyeicosatetraenoic acid) by action of 5-lipoxygenase (5-LOX).
o 5-HPETE is converted to leukotriene-A4, which is unstable, and in turn may be converted to other leukotrienes, or HPETE is rapidly converted to hydroxyl derivatives hydroxyeicosatetraenoic acid (HETEs) and lipoxins.
o Activation of LOX-5 is dependent on 5-LOX-activiating protein (FLAP).

Question 11

LOX-5 pathway

Answer 11

o The leukotrienes produced in this pathway are of interest because of their close association with leukocytes, mast and endothelial cells.
o This pathway is linked to asthma, anaphylactic shock, gout, inflammatory bowl disease and cardiovascular disease

Question 12

Prostaglandin E2 (PGE2) Major effects, functions, and sites of synthesis

Answer 12

o Produced by most cells, especially kidney
o Vasodilation
o Relaxes smooth muscle
o Used to induce labor
o Stimulates uterine contraction
o Required for fever response
o Gastric protection

Question 13

Prostaglandin F2α (PGF2α) Major effects, functions, and sites of synthesis

Answer 13

o Produced in most cells
o Vasoconstriction
o Contraction of smooth muscle
o Stimulates uterine contractions
o Used to induce labor