Effect of endocannabinoids on soybean lipoxygenase-1 activity

Abstract

Endocannabinoids appear to be involved in a variety of physiological processes. Lipoxygenase activity has been known to be affected by unsaturated fatty acids or phenolic compounds. In this study, we examined whether endocannabinoids containing both N-acyl group and phenolic group can affect the activity of soybean lipoxygenase (LOX)-1, similar to mammalian 15-lipoxygenase in physicochemical properties. First, N-arachidonoyl dopamine and N-oleoyl dopamine were found to inhibit soybean LOX-1-catalyzed oxygenation of linoleic acid in a non-competitive manner with a Ki value of 3.7 μM and 6.2 μM, respectively. Meanwhile, other endocannabinoids failed to show a remarkable inhibition of soybean LOX-1. Separately, N-arachidonoyl dopamine and N-arachidonoyl serotonin were observed to inactivate soybean LOX-1 with Kin value of 27 μM and 24 μM, respectively, and k3 value of 0.12 min(-1) and 0.35 min(-1), respectively. Furthermore, such an inactivation was enhanced by ascorbic acid, but suppressed by 13(S)-hydroperoxy-9,11-octadecadienoic acid. Taken together, it is proposed that endocannabinoids containing polyunsaturated acyl moiety and phenolic group may be efficient for the inhibition as well as inactivation of 15-lipoxygenase.

Keywords: 13(S)-hydroperoxyoctadecadienoic acid; 13-HpODE; 15(S)-HpETE; 15(S)-hydroperoxyeicosatatraenoic acid; E(ox); E(red); Endocannabinoids; Inactivation; Inhibition; LOX; N-acyl dopamine; N-arachidonoyl dopamine; N-arachidonoyl glycine; N-arachidonoyl serine; N-arachidonoyl serotonin; N-arachidonoyl taurine; N-oleoyl dopamine; N-palmitoyl dopamine; NA-5HT; NA-DA; NA-Gly; NA-Ser; NA-Tau; NO-DA; NP-DA; Soybean lipoxygenase-1; active ferric enzyme form; inactive ferrous enzyme form; lipoxygenase.