Docosahexaenoic acid is a strong inhibitor of prostaglandin but not leukotriene biosynthesis.

Docosahexaenoic acid (DCHA), a major polyunsaturated acid component of fish lipid, is not a substrate for prostaglandin synthetase from ram seminal vesicles but is a strong competitive inhibitor (Ki, 0.36 microM) of the conversion by this enzyme of arachidonate (Km, 5.9 microM) to prostaglandins. In contrast, DCHA exhibits little interference to the conversion of arachidonate to metabolites on the leukotriene pathway. DCHA is a very poor substrate for the leukotriene-synthesizing system from RBL-1 cells and no formation of the C22 analog of leukotriene B could be detected from it. The C22 analog of leukotriene C4 was produced by chemical synthesis from DCHA and found to be less than 1/10,000th as active as leukotriene C4 in contracting guinea pig ileum. The DCHA used in this work was obtained in greater than 99.8% purity by a practical process developed for its separation from fish lipid. The cardiovascular protective effects ascribed to dietary intake of fish lipid by certain populations may be due in part to the biological action of DCHA, including the inhibition of prostaglandin biosynthesis.