Arachidonic acid metabolism

Arachidonic acid (AA - 5,8,11,-14-eicosatetraenoic acid) is released from cellular phospholipids by the activity of various phospholipases and subsequently metabolized, either through the cyclooxygenase pathway or through the lipoxygenase pathways. Via the cyclooxygenase pathway free AA reacts enzymatically with molecular oxygen to form the unstable cyclic endoperoxides, PGG2 and PGH2, which enzymatically are converted to PGE2 and PGF2a, the most important AA-metabolites in the intestine and to PGD2, prostacycline (PGI2), and thromboxane (TXA2). Alternatively, AA is oxygenated via the lipoxygenase pathways leading to monohydroxylated fatty acids (HETEs) and leukotrienes (LTs). These metabolites are extremely active compounds, covering a large variety of biological effects depending on the cell- or tissue type involved. This project focuses specifically on the gastrointestinal tract, with special reference to the significance of AA-metabolites on cytoprotection, intestinal secretion, and inflammation. In addition, the clinical and pharmacologic effects of specific inhibitors are studied.