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    Eicosanoids: (Prostaglandins, Thromboxanes, Leukotrienes)

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    BOsch Vakil
    This document discusses eicosanoids, which are derived from polyunsaturated fatty acids and act as paracrine messengers. There are several major classes of eicosanoids, including prostaglandins, thromboxanes, and leukotrienes, which are produced through the cyclooxygenase and lipoxygenase pathways from arachidonic acid. Eicosanoids have a wide range of functions, including mediating inflammation and pain, regulating smooth muscle and platelet activity, and more. Nonsteroidal anti-inflammatory drugs work by inhibiting the enzymes responsible for eicosanoid production.

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    Eicosanoids: (Prostaglandins, Thromboxanes, Leukotrienes)

    Uploaded by

    BOsch Vakil
    201 views26 pages
    This document discusses eicosanoids, which are derived from polyunsaturated fatty acids and act as paracrine messengers. There are several major classes of eicosanoids, including prostaglandins, thromboxanes, and leukotrienes, which are produced through the cyclooxygenase and lipoxygenase pathways from arachidonic acid. Eicosanoids have a wide range of functions, including mediating inflammation and pain, regulating smooth muscle and platelet activity, and more. Nonsteroidal anti-inflammatory drugs work by inhibiting the enzymes responsible for eicosanoid production.

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    This document discusses eicosanoids, which are derived from polyunsaturated fatty acids and act as paracrine messengers. There are several major classes of eicosanoids, including prostaglandins, thromboxanes, and leukotrienes, which are produced through the cyclooxygenase and lipoxygenase pathways from arachidonic acid. Eicosanoids have a wide range of functions, including mediating inflammation and pain, regulating smooth muscle and platelet activity, and more. Nonsteroidal anti-inflammatory drugs work by inhibiting the enzymes responsible for eicosanoid production.

    Copyright:

    Attribution Non-Commercial (BY-NC)
    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    201 views26 pages

    Eicosanoids: (Prostaglandins, Thromboxanes, Leukotrienes)

    Uploaded by

    BOsch Vakil
    This document discusses eicosanoids, which are derived from polyunsaturated fatty acids and act as paracrine messengers. There are several major classes of eicosanoids, including prostaglandins, thromboxanes, and leukotrienes, which are produced through the cyclooxygenase and lipoxygenase pathways from arachidonic acid. Eicosanoids have a wide range of functions, including mediating inflammation and pain, regulating smooth muscle and platelet activity, and more. Nonsteroidal anti-inflammatory drugs work by inhibiting the enzymes responsible for eicosanoid production.

    Copyright:

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    Download as PPT, PDF, TXT or read online from Scribd
    Download as ppt, pdf, or txt
    of 26

    EICOSANOIDS

    (prostaglandins, thromboxanes, leukotrienes)

    Eicosanoids
    Major classes of eicosanoids. Precursors of eicosanoids. Major pathways of eicosanoid synthesis (cyclooxygenase and lipoxygenase). Important functions of eicosanoids. Important inhibitors of eicosanoid synthesis

    Eicosaniods
    Derived from 20-crabon polyunsaturated fatty acids Paracrine or autocrine messengers molecules Short half-lives (10 secs 5 mins) so that functions are usually limited to actions on nearby cells. Bind to specific cell surface G-protein coupled receptors, and generally increase cAMP levels. May also bind to nuclear receptors and alter gene transcription. Wide variety of functions

    Major Classes of Eicosanoids


    Prostaglandins Thromboxanes Prostacyclins Leukotrienes HETES

    Effects of Eicosaniods
    Induction of inflammation Mediation of pain signals Induction of fever Smooth muscle contraction (including uterus) Smooth muscle relaxation Protection of stomach lining Simulation of platelet aggregation Inhibition of platelet aggregation Sodium and water retention

    Precursors of Eicosanoids

    Arachidonic acid (6)


    Eicosatrienoic acid (g-linolenic acid, 6) Eicosapentaenoic Acid (3)

    Dietary Linoleic Acid (C18: 9,12) (from plant oils)


    Elongase Desaturase Arachidonic Acid (C20: 5, 8, 11, 14)

    Membrane Phospholipids

    Arachidonic acid release from membrane lipids


    Stimulus

    Phosphatidyl choline
    Phospholipase A2 Ca++ Arachidonic acid

    Phosphatidylinositol bisphosphate
    Phospholipase C
    1,2 Diacylglycerol DAG lipase

    Arachidonic acid

    Monoacylglycerol
    MAG lipase

    Arachidonic acid

    Pathways for Arachidonic Acid Metabolism Arachidonic acid


    Cyclo-oxygenase Pathway lipoxygenase Pathway

    PGG2

    HPETE

    Leukotrienes Lipoxins Prostaglandins Thromboxanes HETE

    Prostaglandins Structural Features

    PGA, PGD, PGE, PGF, PGG, PGH, PGI Depending on the functional groups present at X and Y PGF 1, 2 or 3 Depending on the number of double bonds present in the linear hydrocarbon chain

    PGF 1, 2 or 3

    Thromboxane A2 (TXA2) - structure

    CYCLO-OXYGENASE PATHWAY
    PG and TX synthesis

    PGD synthase PGD 2


    PGE synthase PGE 2
    2GSH 2GSSG

    PGE 9-keto reductase

    PGF2a
    PGI synthase PGI 2 TXA synthase

    TXA2

    Some Functions of Prostaglandins


    PGI2, PGE2, PGD2 Vasodilation, cAMP Platelet and leukocyte aggregation, IL1 and IL2, T-cell proliferation, lymphocyte migration PGF2a Vasoconstriction, Bronchoconstriction, smooth muscle contraction TXA2 Vasoconstriction, Platelet aggregation, lymphocyte proliferation, bronchoconstriction

    Lipoxygenase pathway

    Some Functions of Leukotrienes


    LTB4 Vascular permeability, T-cell proliferation, leukocyte aggregation, IL -1, IL-2, IFN-g

    LTC4 and LTD4 Bronchoconstriction, Vascular permeability, IFN-g

    Leukotrienes and allergies


    Leukotrienes are a hundred times more potent than histamine Histamine provided a rapid response to an allergen In the later stages leukotrienes are principally responsible for inflammation, smooth muscle constriction, constriction of the airways and mucous secretion form mucosal epithelium

    Anti inflammatory Drugs inhibit Eicosanoid Synthesis


    Membrane lipids
    Steroids

    Phospholipase A2

    NSAIDs

    Arachidonic Acid

    Prostaglandins, thromboxanes

    Leukotrienes

    Mechanism of Aspirin Action

    Aspirin and cardiovascular disease


    Low dose aspirin has an anti thromobogenic effect and lowers the risk of heart attacks and strokes. It inhibits the formation of TXA2 in platelets, by inhibition of COX-1 which cannot be overcome because platelets have no nucleus. Endothelial cells have a nucleus and synthesis more COX-1 enzyme needed for the normal prostaglandin functions

    Omega-6/omega-3 fatty acid balance


    w6 and w3 are not interconvertible in humans (mammals). Diets rich in w3 fatty acids result in high content of these fatty acids in membrane phospholipids

    Recommended ratio: 1-4: 1 (w6 : w3)


    Typical western diet: 14-25: 1 (w6 : w3)

    Omega-6/omega-3 fatty acid balance


    A diet rich in omega-6 FAs shifts the physiological state to one that is proinflammatory, prothrombotic and proaggregatory leading to heart disease in susceptible individuals

    Thank you!

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