DCF and IBU in radish [27, 37]. Mefenamic acid (MFA) with its benzoic acid core
was oxidatively metabolized in 3-methylhydroxy MFA [40] at the methylphenyl
ring to the benzylic alcohol. Both compounds can then serve as substrates for
glycosylation to generate MFA-Hex-Mal and OH-MFA-Hex-Mal [40]. By contrast,
treatment of Lepidium sativum with ketoprofen allowed only to detect the hexosyl
malonyl conjugate, while no evidence for any oxidative pathways could be
provided [40].
An analogous reaction of the hydroxyl group with a carboxylic acid of the
glycosylated phase II conjugates is performed by acetylation [52]. The acetylation
of TCS and IBU hexosides in one OH-group of the glycone part gave rise to the
acetylhexoside in radish [27, 46, 52]. Sulfation of glucosides in plants was also
reported [57]. So far, TCS is the only glycosylated compound that was shown to
generate sulfo- and disulfosaccharide conjugates in plants [52].
3.2.3 Amino Acid Conjugates
The reaction of drugs to form amino acid conjugates is an infrequent reaction in
human drug metabolism observed mostly for carboxylic acids to yield taurine or
glycine conjugates. By contrast, plants appear to be more susceptible to form amino
acid conjugates. For instance, drugs, bearing a carboxyl group such as DCF [37],
IBU [41], and NPX [41], form conjugates with glycine, glutamine, leucine, and
phenylalanine. For example, IBU was conjugated directly with glutamine and
glutamic acid to form IBU-Gln and IBU-Glu [41]. Hydroxy-IBU likewise formed
their respective conjugates as well as the one with serine (Table 1). These results,
together with findings for NPX, clearly show that conjugation with amino acids,
especially Glu and Gln, was a major route of biotransformation of profens in
Arabidopsis [41]. Amino acid conjugation though is not limited to substrates with
carboxyl group to yield the amide, but it was also observed for the secondary amine
in N-desmethyl SRT in garden grass treated with SRT whose carboxylic acid
functionality reacted with the aromatic amino acids tyrosine and phenylalanine
[34]. The formation of AAP-Cys did not originate from a direct reaction with
cysteine but was formed by two consecutive hydrolytic steps of the two amide
bonds which yielded glutamic acid from the phase II metabolite, AAP-Glu, already
formed in Armoracia rusticana [26].
3.3 Phase III Plant Metabolism
To get rid of phase II products, plants transport them into the vacuole where they are
stored or incorporate them to the cell wall. This phase III of compartmentation is
unique to plants because plants cannot excrete xenobiotics as animals do. Phase III
products are no longer toxic for plants but can be reconverted in the original phase II
or even phase I metabolites after ingestion by herbivores or after reincorporation of
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A. Sauvêtre et al.
was oxidatively metabolized in 3-methylhydroxy MFA [40] at the methylphenyl
ring to the benzylic alcohol. Both compounds can then serve as substrates for
glycosylation to generate MFA-Hex-Mal and OH-MFA-Hex-Mal [40]. By contrast,
treatment of Lepidium sativum with ketoprofen allowed only to detect the hexosyl
malonyl conjugate, while no evidence for any oxidative pathways could be
provided [40].
An analogous reaction of the hydroxyl group with a carboxylic acid of the
glycosylated phase II conjugates is performed by acetylation [52]. The acetylation
of TCS and IBU hexosides in one OH-group of the glycone part gave rise to the
acetylhexoside in radish [27, 46, 52]. Sulfation of glucosides in plants was also
reported [57]. So far, TCS is the only glycosylated compound that was shown to
generate sulfo- and disulfosaccharide conjugates in plants [52].
3.2.3 Amino Acid Conjugates
The reaction of drugs to form amino acid conjugates is an infrequent reaction in
human drug metabolism observed mostly for carboxylic acids to yield taurine or
glycine conjugates. By contrast, plants appear to be more susceptible to form amino
acid conjugates. For instance, drugs, bearing a carboxyl group such as DCF [37],
IBU [41], and NPX [41], form conjugates with glycine, glutamine, leucine, and
phenylalanine. For example, IBU was conjugated directly with glutamine and
glutamic acid to form IBU-Gln and IBU-Glu [41]. Hydroxy-IBU likewise formed
their respective conjugates as well as the one with serine (Table 1). These results,
together with findings for NPX, clearly show that conjugation with amino acids,
especially Glu and Gln, was a major route of biotransformation of profens in
Arabidopsis [41]. Amino acid conjugation though is not limited to substrates with
carboxyl group to yield the amide, but it was also observed for the secondary amine
in N-desmethyl SRT in garden grass treated with SRT whose carboxylic acid
functionality reacted with the aromatic amino acids tyrosine and phenylalanine
[34]. The formation of AAP-Cys did not originate from a direct reaction with
cysteine but was formed by two consecutive hydrolytic steps of the two amide
bonds which yielded glutamic acid from the phase II metabolite, AAP-Glu, already
formed in Armoracia rusticana [26].
3.3 Phase III Plant Metabolism
To get rid of phase II products, plants transport them into the vacuole where they are
stored or incorporate them to the cell wall. This phase III of compartmentation is
unique to plants because plants cannot excrete xenobiotics as animals do. Phase III
products are no longer toxic for plants but can be reconverted in the original phase II
or even phase I metabolites after ingestion by herbivores or after reincorporation of
242
A. Sauvêtre et al.