Eicosanoid Metabolism

Describe the mode of action of eicosanoids

(autocrine, paracrine). G-protein coupled receptors; receptor binding activates the cAMp protein kinase A system or causes an increase in cytosolic calcium usually a g protein coupled receptor for prostaglandin and thromboxane

physiological activities of eicosanoids

Eicosanoids exhibit a large variety of different physiological activities affecting all (most?) tissues in the body (NOT RBC); often acting in a tissue-specific manner. Always act locally! (pain, fever, swelling, inflammation, smooth muscle contraction/relaxation, platelet aggregation, allergy, secretion, growth, chemotaxis, ion transport

Describe the intracellular location (origin) of the polyunsaturated fatty acids (pufa) used to synthesize eicosanoids.

Extracellular signals activate cell surface receptorsthereby stimulating pathways that initiate Eicosanoid synthesis from membrane bound C20 fatty acids (3, 4 or 5 double bonds, omega-3 or omega-6). ARACHIDONIC ACID/ EICOSATRIENOIC ACID / EICOSAPENTAENOIC ACID

Name the class of eicosanoids which contain amino acid residues

Leukotrienes is HPETE with the tripetide glutathione Glu-Cys-Gly

Recognize the names of the major pathways/classes of eicosanoids

cyclooxygenase(COX1/2) pathway leads to synthesis of prostaglandins and thromboxanes, lipoxygenase pathway leads to synthesis of leukotrienes;HETE; diHETE;and lipoxins/trihydroxyETE, cytochrome P450 leads to 20-HETE and Epoxy ETE, resolvins, protectins, and maresins

(Extra credit) Describe 3 or 4 clinical applications of eicosanoids?

modulate calcium transport regulate cell growth and death (apoptosis) abnormal nuclear eicosanoid receptor (PPARg) in colonic cancers renin-angiotensin-dependent hypertension regulation in human breast cancer cell line excretion in hepatic cirrhosis oxygen radical injury motility of prostate tumor cells immediate hypersensitivity (allergic reaction, food hypersensitivity) bronchial asthma, nasal congestion, allergic rhinitis inflammation in psoriasis inflammation in rheumatoid arthritis chronic inflammatory bowel disease maintain patency of ductus arteriosus (fetus) promote smooth muscle contraction in pulmonary airways, trachea and intestine during anaphylaxis promote tumor cell adhesion to vascular endothelium

List the general types (broad classes) of eicosanoids.

prostaglandins and thromboxanes(cyclooxygenase pathway) ; leukotrienes diHETE HETE Lipoxins from (lipoxygenase pathway); HETE and Epoxy ETE from Cyt P450 pathway

Describe the clinical role of the resolvins, protectins, and maresins.

reolvins and protectins: Anti-inflammatory compounds made from eicosapentanoic acid (EPA) and docoshexanoic acid (DHA). Promote the resolution of inflammation. protectins and maresins: New pro-resolving families of mediators in acute inflammation and resolution bioactive metabolome resolvins and protectins promote resolution of the inflammation through removal of the leukocytes together with cellular debris; some immunoregulatory activities;contribute to removal of inflammatory cells and restoration of tissue integrity once the need for the inflammatory response is ove

eicosanoid definition

signaling molecules made by oxidation of twenty-carbon fatty acids. They exert complex control over many bodily systems, mainly in inflammation or immunity, and as messengers in the central nervous system. The networks of controls that depend upon eicosanoids are among the most complex in the human body."

Eicosanoids

small organic molecules derived from membrane-bound, polyunsaturated C20 fatty acids (e.g. arachidonic acid) which have very potent biological and hormone-like activities

mechanism of eicosanoid action

they are local hormones that act through a g protein coupled receptor more often that not

Recognize the names of the fatty acid precursors of eicosanoids.

two essential fatty acids (Linoleic Acid, alpha-Linolenic Acid) and some of their derivatives involved in Eicosanoid synthesis. Arachidonic acid and Eicosapentaenoic acid are two major precursors of the eicosanoids.

Discuss the general physiological/biological activities of eicosanoids.

1)Bind to cell surface receptors and stimulate signal transduction pathways 2) Variety of activities in different tissues 3) autocrine and paracrine action 4) generally short lived and thought to be metabolized in the lung

_____ plays an important physiological role in the kidney brain, lungs and GI

20 HETE

catalyzes the first reaction in the pathway leading to the synthesis of prostaglandins and thromboxanes in ERERERERER

Prostaglandin H2 Synthase Complex has two enzymatic activities (Cyclooxygenase or COX and Hydroperoxidase).

describe the biological and medical importance of leukotrienes

induce contraction of the muscle lining in the airways of the lung. overproduction causing asthmatic, strong contraction of the smooth muscle of lungs occurs during anaphylactic shock, stimulate pro inflammatory activities, mediate inflammation and induce asthma or other inflammatory disorders reducing airflow

Discuss the eventual metabolic fate (catabolism) of eicosanoids.

it is believed that eicosanoids are eventually metabolized in the lung