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Eicosanoids
USCSOM: Eicosanoid metabolism
| Question | Answer |
|---|---|
| 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