Inhibition of leukotriene biosynthesis by acetylenic analogs

The monoacetylenic acid, 5,6-dehydroarachidonic acid (5,6-DHA), inhibits the 5-lipoxygenase in RBL-1 extracts in a time-dependent irreversible manner. In intact cell systems, 5,6-DHA is not as effective as ETYA or 15(S)-HEYA in inhibiting the 5-lipoxygenase activities, because 5,6-DHA is metabolized into triglycerides, phospholipids and hydroxylated products. While lipoxygenation of arachidonic acid at C-5 and C-12 is inhibited by 15-HETE, the transformation of arachidonic acid into 5,15-diHETE via 15-HPETE in human leukocytes is relatively insensitive to 15-HETE.