Inhibition of soybean lipoxygenase and mouse skin tumor promotion by onion and garlic components
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1Institute of Environmental Medicine, New York University Medical Center, New York 10016.
Abstract:
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 Ki = 59 microM and k3 = 0.53/min. Inhibition in the presence of substrate was uncompetitive at 88 and 132 microM linoleic acid with Ki = 129 microM. At 173 microM linoleic acid, however, inhibition was competitive with Ki = 66 microM. 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 Ki = 0.29 microM. The results indicate a relative potency of inhibition for structural features in the following order: di(1-propenyl) sulfide greater than an alkenyl trisulfide greater than 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 antipromotion.
Insights
Onion and garlic compounds, particularly di-(1-propenyl) sulfide, inhibit soybean lipoxygenase (EC 1.13.11.12). This enzyme inhibition by specific sulfur compounds suggests a role in the anti-tumor promotion effects of these vegetables.
Area of Science:
- Biochemistry
- Enzymology
- Natural Products Chemistry
Background:
- Onion and garlic essential oils exhibit anti-tumor promotion activity in mouse skin.
- Lipoxygenase (LOX) and cyclooxygenase (COX) enzymes are implicated in tumor promotion pathways.
Purpose of the Study:
- To investigate the inhibition of soybean lipoxygenase (EC 1.13.11.12) by components of onion and garlic.
- To determine the kinetic parameters and relative potency of various sulfur-containing compounds as LOX inhibitors.
Main Methods:
- Enzyme inhibition assays were performed using soybean lipoxygenase.
- IC50 values and kinetic inhibition constants (Ki, k3) were determined for active compounds.
- Linoleic acid was used as a substrate to analyze inhibition mechanisms (competitive, uncompetitive, mixed).
Main Results:
- Di-(1-propenyl) sulfide was identified as an irreversible inhibitor (Ki = 59 µM, k3 = 0.53/min) and a mixed inhibitor at higher substrate concentrations.
- Diallyl trisulfide, allyl methyl trisulfide, and diallyl disulfide acted as competitive inhibitors.
- Nordihydroguaiaretic acid (NDGA) showed potent competitive inhibition (Ki = 0.29 µM).
- Inhibitory potency followed the order: di(1-propenyl) sulfide > alkenyl trisulfide > alkenyl disulfide.
Conclusions:
- Specific sulfur compounds in onion and garlic, notably di-(1-propenyl) sulfide and ajoene, effectively inhibit soybean lipoxygenase.
- The observed lipoxygenase inhibition by these compounds supports their potential role in the anti-promotional effects of onion and garlic.
- Di(n-propyl) disulfide, a major onion oil component, did not inhibit lipoxygenase, suggesting structural specificity for inhibitory activity.