Phase III
PHASE III
Phase III reactions are unique to plants because plants do not excrete xenobiotics as animals do. Plants therefore, need to somehow remove the xenobiotic within their own system. Plants do this by either: - conjugating Phase II products further - moving metabolites to the vacuole for storage - incorporating the metabolite into the cell wall region.
It is assumed that Phase III products are no longer toxic; however, this area of xenobiotic fate in plants is poorly understand, especially with reference to the identity of sequestered products and any subsequent fate in herbivores who consume the plants.
Fig. 30: Secondary Conjugation
Fig. 31: Malonic acid residue is attached to a product from Phase II sugar conjugation
Secondary conjugation (Figure 30) - Herbicide glucosides can be further processed by the addition of a malonic acid residue to the sugar conjugate. In secondary conjugation or malonyl CoA conjugation, a malonic acid residue is attached to a product from Phase II sugar conjugation by an ester linkage (Figure 31). Malonyl CoA is the acyl donor (3 carbons will be added to the sugar conjugate) and the reaction is catalyzed by malonyl-CoA-transferases. Because malonyl conjugates are labile during extraction and purification, there may be more examples of secondary conjugation than currently identified in the literature. Malonylation may enhance vacuolar sequestration as well. When a xenobiotic is conjugated to glutathione, it can be catabolized to cysteine by the removal of the glutathione’s glutamate and glycine groups, prior to conjugation with malonate.
Insoluble residues - Pesticide metabolites may also be incorporated into cell wall material (Figure 32). These are known as insoluble or bound residues because they cannot be removed using conventional solvent extraction techniques. In general, terminal conjugation to insoluble or bound residues is not well understood, but studies have shown that between 1 and 70 % of the herbicide metabolite can be incorporated into structural components of the plant. This wide variation is thought to be due to differences in the xenobiotic, the plant species or tissue studied and the time of harvest. Xenobiotics sensitive to this fate usually contain aromatic or heterocyclic rings. An example of hydroxy-polychlorophenol (OH-PCP) incorporation into lignin is shown in Figure 33. Lignin is a polymer of phenolic groups. Peroxidases in the cell wall region create a free radical on the lignin molecule (at the highlighted -OH, for example) to which the OH-PCP can attach (Figure 33a). The PCP is essentially bound irreversibly.
Fig. 32: A sugar conjugate of a pesticide (X) which has been bound to cell wall material
Fig. 33a: Lignin (left) and OH-PCP (right) in the cell wall regions
Fig. 33b: Insoluble residue of PCP
Vacuolar sequestration (Figure 34) - Because plants store many toxic metabolites in their vacuoles and these toxic metabolites are released upon herbivore attack, it has long been thought that xenobiotic metabolites are moved into the vacuole. Recent evidence suggests there is a carrier on the vacuole membrane which recognizes glutathione conjugates (GS-X), transporting them into the vacuole (Figure 35). The carrier is dependent on ATP and apparently transports many glutathione conjugates (xenobiotics and natural products) into the vacuole. Glutathione and its conjugates are predominately anionic at the high pHs found in the cytoplasm of plant cells and therefore, rely on a transporter to move across the lipophilic membrane. To date, only a few glutathione conjugates have been shown to accumulate in plant vacuoles. No transporters of amino acids or glucose conjugates have been identified on vacuolar membranes. Malonylation may aid in vacuolar sequestration as well.
Fig. 34: Vacuolar sequestration
Fig. 35: A glutathione conjugate (GS-X) being transported into the vacuole
Name three ways plants deal with pesticide metabolites in Phase III reactions, instead of excreting the pesticide metabolite like animals do.
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