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18
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The Eicosanoids:

Prostaglandins,

Thromboxanes,

Leukotrienes, & Related

Compounds

*
John Hwa, MD, PhD, & Kathleen Martin, PhD

C ASE STUD Y

A 40-year-old woman presented to her doctor with pulmonary pressures, and right ventricular enlargement.
a 6-month history of increasing shortness of breath. Cardiac catheterization confirmed the severely elevated
This was associated with poor appetite and ankle swell- pulmonary pressures. She was commenced on appropri-
ing. On physical examination, she had elevated jugular ate therapies. Which of the eicosanoid agonists have been
venous distention, a soft tricuspid regurgitation murmur, demonstrated to reduce both morbidity and mortality in
clear lungs, and mild peripheral edema. An echocardio- patients with such a diagnosis? What are the modes of
gram revealed tricuspid regurgitation, severely elevated action?

The eicosanoids are oxygenation (oxidation) products of poly- ARACHIDONIC ACID & OTHER
unsaturated 20-carbon long-chain fatty acids (eicosa, Greek POLYUNSATURATED PRECURSORS
for “twenty”). They are ubiquitous in the animal kingdom and
are also found—together with their precursors—in a variety of Arachidonic acid (AA), or 5,8,11,14-eicosatetraenoic acid, the
plants. They constitute a very large family of compounds that most abundant of the eicosanoid precursors, is a 20-carbon (C20)
are highly potent and display an extraordinarily wide spectrum fatty acid containing four double bonds (designated C20:4–6).
of important biologic activities. Thus, their specific receptors, The first double bond in AA occurs at 6 carbons from the methyl
receptor ligands, and enzyme inhibitors, and their plant and end, defining AA as an omega-6 fatty acid. AA must first be released
fish oil precursors, are therapeutic targets for a growing list of or mobilized from the sn-2 position of membrane phospholipids
conditions. by one or more lipases of the phospholipase A (PLA ) type
2
2
(Figure 18–1) for eicosanoid synthesis to occur. The phospho-
superfamily consists of 16 groups (over 30 isoforms),
lipase A 2
* The authors thank Emer M. Smyth, PhD, and Garret A. FitzGerald, MD, with at least three classes of phospholipases contributing to ara-
for their contributions to previous editions of this chapter. chidonate release from membrane lipids: (1) cytosolic (c) PLA ,
2

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