many recently published studies about the uptake and translocation of environmental
contaminants overlook the concentration of metabolites. Neglecting pharmaceutical
metabolites in environmental studies might lead to a severe underestimation of the
uptake and translocation of pharmaceuticals in plants and eventually to an
underestimated human exposure to these contaminants in food [89]. Therefore, it
is always necessary to perform mass balance analysis because only this can provide
clear-cut information to evaluate the potential metabolic routes of pharmaceuticals in
distinct plant tissues.
Figure 3 displays the current knowledge about the detoxification cascade for
herbicides [90]. While the traditional scheme of herbicide detoxification concluded
in a phase III leading to bound cell wall residues has been well accepted for
agrochemicals as the concept of the “green liver” [80], information on the fate of
non-herbicidal pollutants and pharmaceuticals in plants is only poor and scattered.
However, it can be assumed that pharmaceuticals undergo exactly the same metabolic steps since they possess similar molecular properties and sometimes derive
from identical chemical families (e.g. triazines, sulfonylureas). Since experimental
evidence indicated that xenobiotic glutathione or glucosyl conjugates may inhibit
cytosolic processes [91], it has generally been accepted that xenobiotic conjugates
are sequestered from the cytosol in higher plants during phase III.
2.5 Vacuolar Transport and Sequestration
Considering now the central dogma of xenobiotic metabolism in plants as valid that
conjugation of xenobiotics may not be the end point of metabolism, a deeper look
should be taken into plant storage processes. In fact, it seems that storage may be
only intermediary for many substances and that further breakdown of these polar
derivatives can lead to a complex set of processing reactions (Fig. 3), both in the
vacuole and in the cytoplasm [92, 93]. One of the best studied routes of xenobiotic
conjugate catabolism relates to glutathionylated pesticides [94]. An early report
followed a chloroacetamide herbicide in cereals that could be tracked into the
vacuole, where the respective detoxification products, glutathione conjugates, were
cleaved by a carboxypeptidase to produce γ-Glu-Cys-alachlor conjugates [95].
Hence, it is not unlikely that ABC and MATE transporters in plasmalemma and
tonoplast may also be involved in the detoxification of organic compounds other
than herbicides, since enzymes involved in the synthesis of secondary compounds
may also recognize and modify potentially toxic molecules taken up by the plant.
Subsequently, molecules can yield cell wall residues or be transported into the
vacuole for final detoxification (Fig. 3). Evidence for this latter sequestration step
has been presented for several species and seems to be ubiquitous [96]. In a recent
paper, the uptake and metabolism of the sun shield, oxybenzone, has been followed
in umbrella papyrus (Cyperus alternifolius). Uptake and phase I and II metabolism
followed the green liver concept, and it seems likely that some member of the ABCC
subfamily was responsible for vacuolar delivery of the glutathionated phase II
116
Y. Bigott et al.
contaminants overlook the concentration of metabolites. Neglecting pharmaceutical
metabolites in environmental studies might lead to a severe underestimation of the
uptake and translocation of pharmaceuticals in plants and eventually to an
underestimated human exposure to these contaminants in food [89]. Therefore, it
is always necessary to perform mass balance analysis because only this can provide
clear-cut information to evaluate the potential metabolic routes of pharmaceuticals in
distinct plant tissues.
Figure 3 displays the current knowledge about the detoxification cascade for
herbicides [90]. While the traditional scheme of herbicide detoxification concluded
in a phase III leading to bound cell wall residues has been well accepted for
agrochemicals as the concept of the “green liver” [80], information on the fate of
non-herbicidal pollutants and pharmaceuticals in plants is only poor and scattered.
However, it can be assumed that pharmaceuticals undergo exactly the same metabolic steps since they possess similar molecular properties and sometimes derive
from identical chemical families (e.g. triazines, sulfonylureas). Since experimental
evidence indicated that xenobiotic glutathione or glucosyl conjugates may inhibit
cytosolic processes [91], it has generally been accepted that xenobiotic conjugates
are sequestered from the cytosol in higher plants during phase III.
2.5 Vacuolar Transport and Sequestration
Considering now the central dogma of xenobiotic metabolism in plants as valid that
conjugation of xenobiotics may not be the end point of metabolism, a deeper look
should be taken into plant storage processes. In fact, it seems that storage may be
only intermediary for many substances and that further breakdown of these polar
derivatives can lead to a complex set of processing reactions (Fig. 3), both in the
vacuole and in the cytoplasm [92, 93]. One of the best studied routes of xenobiotic
conjugate catabolism relates to glutathionylated pesticides [94]. An early report
followed a chloroacetamide herbicide in cereals that could be tracked into the
vacuole, where the respective detoxification products, glutathione conjugates, were
cleaved by a carboxypeptidase to produce γ-Glu-Cys-alachlor conjugates [95].
Hence, it is not unlikely that ABC and MATE transporters in plasmalemma and
tonoplast may also be involved in the detoxification of organic compounds other
than herbicides, since enzymes involved in the synthesis of secondary compounds
may also recognize and modify potentially toxic molecules taken up by the plant.
Subsequently, molecules can yield cell wall residues or be transported into the
vacuole for final detoxification (Fig. 3). Evidence for this latter sequestration step
has been presented for several species and seems to be ubiquitous [96]. In a recent
paper, the uptake and metabolism of the sun shield, oxybenzone, has been followed
in umbrella papyrus (Cyperus alternifolius). Uptake and phase I and II metabolism
followed the green liver concept, and it seems likely that some member of the ABCC
subfamily was responsible for vacuolar delivery of the glutathionated phase II
116
Y. Bigott et al.