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USCSOM: Eicosanoid metabolism

What are the 3 main type of eicosanoids? Prostaglandins, thromboxins, leukotrienes
What is meant by autocrine factor? it releases hormones that affect itself
What is meant by paracranine factor? it releases hormones that affects nearby cells
What are the 3 main functions of eicosanoids? Inflammatory response, smooth muscle contraction
Eicosanoids affect smooth muscle contraction in what organs? intestine, bronchioles, blood vessels, pregnant uterus
What is the most common precursor of Eicosanoids? Arachidonate
What is a PUFA? poly unsaturated fatty acid
What are the main dietary PUFAs? linoleate or alpha-linoleate
What enzyme initiates eicosanoid production? phospholipase A2
What is the primary FA released by PLA2? arachidonic acid
What pathway from arachidonic acid produce prostaglandins and thromboxins? cycloxygenase (COX)
What structural features are essential for biological activity in a prostaglandin? trans-C13 and hydroxy-C15
What molecules lead from PL to thromboxin or prostaglandins? Arachidonate, PGG2/PGH2
What is the role of TXA2? platelet aggregation, vasoconstriction, lymphocyte proliferation, bronchoconstriction
What is the role of PGI2? vasodilation, inhibit platelet aggregation
What cyclo-oxygenase is more specific for inflammation and pain? COX-2
What inhibits COX-1? Non-steroidal anti-inflammatory drugs
What drug irreversibly inhibits COX? aspirin; acetylsalicylate
What are effects of COX-1 inhibition toxicity? gastric dysfunction and renal dysfunction
What is the role of PGA2? inhibits acid secretion in intestinal cells
What is the role of PGE2? regulates water and Na+ reabsorption in the kidneys, vasodilation, inhibit IL-1 and IL-2 (inflammation)
What reaction do steroidal anti-inflammatory drugs inhibit? PLA2: phospholipase A2
What is the major inhibitory reaction of non-steroidal anti-inflammatory drugs? COX enzymes
Arachidonic acid released by PLA2 is eicosanoid by what 3 different ways? COX, lipoxygenase, cytochrome P450
Draw PGA, PGD, PGE, PGF-alpha, PGG/PGH, PGI see slide 16
Functions of PGI2 vasodilation (inc. cAMP)
Functions of PGD2 vasodilation, IL-1 and IL-2 (inflammation)inhibitors, attractant for eosinophils (asthma)
Functions of PGF2 vasoconstriction, bronchoconstriction, smooth muscle contraction
How do omega-3 fatty acids work? form TXA3 instead of TXA2, significantly less active platelet aggregator
What 2 things are required to inactivate prostaglandins? oxidation of 15-OH
The lipoxygenase pathway occurs in mainly what kind of cell type? leukocytes
What is LOX? lipoxygenase enzymes
What form of HPETE is the main precursor for most leukotrienes? 5-HPETE
5-HPETE is converted into what in the leukotriene pathway? via what enzyme? Leukotriene A4 via LTA4 synthase
Hydrolysis of LTA4 yields what product? LTB4
What are the functions of LTB4? chemotactic agents for eosinophils and neutrophils, inflammatory response, vascular permeability (edema), increase IL-1 IL-2
What is added to LTA4 to get LTC4? addition of GSH (glutathione)
What happens from LTC4, to LTD4, to LTE4? cleavage of gamma-glutamate and glycine
What are the functions of LTC4 and LTD4? increase bronchoconstriction, vascular permeability, anaphylaxis
What is SRS-A? What molecules make it up? Slow-Reacting Substance of Anaphylaxis
What is LXA4? How is it formed? lipoxin A4, arachidonic acid, 15-lipoxygenase, 5-lipoxygenase, reduction
What are the actions of lipoxins? potent inhibitors of acute inflammation
What does the cytochrome P450 pathway produce from arachidonate? epoxides, 5,6-EET, 5,6-diHETE
What is 5,6-EET? endogenous pulmonary vasodilator
Created by: jlellerm