Effect of endocannabinoids on soybean lipoxygenase-1 activity

• We examined the effect of endocannabinoids on soybean lipoxygenase-1 activity.
• We demonstrate that N-oleoyl dopamine or N-arachidonoyl dopamine inhibited soybean lipoxygenase-1.
• N-arachidonoyl dopamine or N-arachidonoyl serotonin is a strong inactivator of soybean lipoxygenase-1.
• The inactivation was enhanced by ascorbic acid, but suppressed by 13-hydroperoxy-9,11-octadecadienoic acid.

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.

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