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

Abstract

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 (K;, 0.36 ,tM) of the conversion by this enzyme of arachidonate (K., 5.9 ,LM) 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 >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.

Omega-3 fatty acids cause dramatic changes in TLR4 and purinergic eicosanoid signaling

“…In contrast to the inhibitory nature of DHA toward COX AA activity, 5-LOX AA metabolism was previously found to be minimally inhibited by DHA using enzyme derived from RBL-1 cells (9). This presents a potential shunting scenario which we were able to observe.…”

“…Greater inhibition of COX-1 vs. COX-2 with ω3 PUFA supplementation is consistent with decreased platelet aggregation and longer bleeding times in Eskimos and other groups on high marine-fish diets (9,40). Our data suggest that these effects may be because of highly decreased COX-1-derived TxA 2 and PGH 2 by platelets, but endothelial PGI 2 coupled with COX-2 would be inhibited to a significantly lesser extent to shift the vascular eicosanoid balance toward antiplatelet aggregation.…”

“…In addition, their increased presence through supplementation presents the potential to compete for, and inhibit AA eicosanoid production and receptor stimulation, particularly in the COX pathway (8,9). Although DHA is generally considered to be cardioprotective after membrane incorporation via mechanisms that improve receptor and ion channel function, EPA can also be metabolized to resolvin E1, which has recently been demonstrated to have potent cardioprotective action (10).…”

Effects of dietary fatty acids on reproduction in ruminants

“…The PUFAs can also inhibit PGHS synthesis in vitro (Achard et al, 1997), and competitively inhibit the conversion of arachidonic acid to prostaglandins of the 2 series (Corey et al, 1983;Fig. 3).…”

Reduced tumour growth of the human colonic cancer cell lines COLO-320 and HT-29 in vivo by dietary n-3 lipids

“…The mechanism of action of fish oil remains to be elucidated. Possibilities include inhibition of cyclo-oxygenase systems (Culp et al, 1979;Corey et al, 1983) and increased lipid peroxidation (Begin & Das, 1986;Begin & Ells, 1987;Begin et al, 1986Begin et al, , 1988Cheeseman et al, 1986). Moreover, in investigating these mechanisms it will be necessary to determine whether the effects are due to a specific n-3 fatty acid and conversely whether similar effects are obtained with n-6 fatty acids.…”