Phase I - Oxidation Reactions
These Phase I reactions result in either detoxication or activation of the herbicide. Many of these oxidative reactions are presumed to be catalyzed by cytochrome P-450 monooxygenases. Monoxygenases catalyze reactions in which one of the two atoms of molecular oxygen is incorporated into the substrate (e.g. herbicide or xenobiotic) and the atom is reduced to water by an electron donor, such as NADPH (equation 1).
X + RH2 + O2 → X-O + H2O + R
Where, X is the substrate (e.g. xenobiotic, herbicide), RH2 is the reduced cofactor such as NADPH, O2 is required as the second substrate, X-O is the oxygenated product and RH is the oxidized cofactor. Cytochrome P-450 monooxygenases are usually membrane bound and xenobiotic metabolism occurs in the endoplasmic reticulum.
Examples of oxidation reactions include N-dealkylation or N-demethylation (Figure 2), O-dealkylation (Figure 3), aromatic hydroxylation (Figure 4), thioether oxidation (Figure 5) and β-oxidation (Figure 6).
Some insecticides (organophosphates) can act as suicide substrates, irreversibly binding to cytochrome P450s in the plant and rendering the crop more sensitive to some herbicides (e.g. sulfonylureas). On the other hand, safeners or antagonists are able to induce (increase) cytochrome P450 monooxygenases in protected grass crops and therefore, enhance metabolism of some herbicides in the aryloxyphenoxypropionate, sulfonylurea, imidazolinone and sulfonamide families.
Can inhibiting the enzymes that detoxify pesticides, alter the pesticide’s toxicity?
Answer: Yes. If cytochrome-P450 enzymes are inhibited, Phase I reactions will not occur, and pesticides will not be made less toxic. Alternately, pesticide activity can be lowered if these enzymes are turned on to work better.