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Chapter 22: Lipids: The Eicosanoids: Prostaglandins, Leukotrienes, and Thromboxanes

You are investigating a novel series 1 prostaglandin inhibitor on the activity of a section of femoral artery in culture. You have shown that the inhibitory compound directly interferes with the action of PGE1. Which of the following activies is most likely reduced or absent in your organ culture system in the presence of this inhibitor?

A. activation of 5-LOX for leukotriene synthesis

B. enhancement of neutrophil adhesion

C. induction of slow cardiac contraction

D. platelet aggregation and activation

E. relaxation of vascular smooth muscle cells

Answer E: PGE1 is a series 1 eicosanoid derived from linoleic acid or γ-linolenic acid (GLA). This lipid induces vasodilation through relaxation of smooth muscle cells, exhibits anti-inflammatory activity, and inhibits platelet aggregation.

Cells isolated from the lungs of experimental mice via alveolar lavage are being studied for their responses to various lipid molecules. Results indicate that addition of arachidonic acid leads to increased production of PGE2 but that LTA4 is not detected. Which of the following enzymes is most likely defective explaining the observed results?

A. COX-1

B. 5-LOX

C. LTC4 synthase

D. prostacylin synthase

E. thromboxane synthase

Answer B: LTA4 is an intermediate in the linear eicosanoid synthesis pathway. The linear pathway is initiated through the action of LOXs of which there are 3 forms: 5-LOX, 12-LOX, and 15-LOX. It is 5-LOX that gives rise to the leukotrienes. Therefore, loss of LTA4 detection would most likley be due to loss of 5-LOX activity given that arachidonic acid was utilized effectively as a cyclic pathway (PGE2) substrate.

You are studying the effects of a novel compound in a variety of vascular and immune system assays. Your results demonstrate that the compound exhibits actitivies very similar to a previously identified eicosanoid. These activities include inhibition of platelet and leukocyte aggregation, induction of smooth muscle relaxation, decreased proliferation of T cells, decreased lymphocyte migration, and decreased secretion of IL-1α and IL-2. Which of the following eicosanoids exhibits biological activities most closely resembling those of your test compound?






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