Have Enzymes of the "Third Pathway" been demonstrated in the Gut?

Do the enzymes metabolise AA and what particular metabolites are produced in the Gastrointestinal Tract?

Do the metabolites produced have biological activity on the intestinal tract?



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Cytochrome P450 Metabolites of Arachidonic Acid: Potential Roles in Intestinal Ion Transport.

E. Schleihauf
(Honours Biology-Pharmacology Co-op Programme, McMaster University, Hamilton, ON. Canada)
T. Prior
(Intestinal Disease Research Programme, McMaster University, Hamilton, ON, Canada)
P.K. Rangachari
(Intestinal Disease Research Programme, McMaster University, Hamilton, ON, Canada)

Contact Person: P.K. Rangachari (chari@mcmaster.ca)


Oxygenation reactions involving arachidonic acid generate biologically-active mediators. Three pathways have been described. Much attention has been focused on the products of the cyclo-oxygenase and lipoxygenase pathways but gastrointestinal pharmacologists have paid less attention to the products of the "third" pathway - the epoxygenase pathway. Metabolism by the cytochrome P450-dependent monooxygenase system occurs in three ways:(a) epoxidation producing (5,6-), (8,9-), (11,12-), and 14,15-epoxyeicosatrienoic acids (EETs), (b) allylic oxidation, resulting in the formation of (5-), (8-), (9-), (11-), (12-), and15-hydroxyeicosatetraenoic acids (HETEs) and (c) hydroxylation leading to the formation of (19-) and 20-HETES, and 20-carboxyl arachidonic acid. These products can be biologically active. This review will summarise current information and highlight potential roles in modulating intestinal ion transport. ( Supported by MRC Canada)

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Poster Number SAschleihauf0148
Keywords: cytochrome P450, Arachidonic Acid, EET, GI, epoxygenase

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