Inhibition of soybean lipoxygenase and mouse skin tumor promotion by onion and garlic components

Onion and garlic essential oils were previously shown to inhibit mouse skin tumor promotion, as were the enzymes, lipoxygenase, and cyclooxygenase. In the present study, the inhibition of soybean lipoxygenase (EC 1.13.11.12) by onion and garlic components and related compounds was investigated. The IC₅₀ values as well as the kinetic inhibition constants were determined for the most active compounds. Di‐(1‐propenyl) sulfide, an analog of the substrate moiety required for oxygenase action, was the only irreversible inhibitor observed with K_i =59 μM and k₃ =0.53/min. Inhibition in the presence of substrate was uncompetitive at 88 and 132 μM linoleic acid with K_i =129 μM. At 173 μM linoleic acid, however, inhibition was competitive with K_i =66 μM. Dially trisulfide, allyl methyl trisulfide, and diallyl disulfide were competitive inhibitors, while 1‐propenylpropyl sulfide and (E, Z)‐4,5,9‐trithiadodeca‐1,6,11‐triene 9‐oxide (ajoene) were mixed inhibitors. Nordihydroguaiaretic acid (NDGA), the most potent lipoxygenase inhibitor, was a competitive inhibitor with K_i =0.29 μM. The results indicate a relative potency of inhibition for structural features in the following order: di(1‐propenyl) sulfide > an alkenyl trisulfide > an alkenyl disulfide. Di(n‐propyl) disulfide, a major onion oil component, inhibited neither lipoxygenase nor promotion. Di(1‐propenyl) sulfide and ajoene inhibited both. This suggests that the inhibition of lipoxygenase may be involved in anti‐promotion.