Introduction to Biotransformation (Metabolism) - Pesticide Biotransformation and Disposition - page 68

Cysteine Conjugate β -Lyase
This enzyme uses cysteine conjugates as substrates, releasing the thiol derivative of the
original xenobiotic, ammonia, and pyruvic acid, the thiol derivative then undergoing
S-methylation to give rise to the methylthio derivative.
Acylation
Acylation reactions are of two types, the first involving transfer of an acetyl group by
acetyl-CoA, the second involving activation of the xenobiotic and subsequent reac-
tion with an amino acid. Deacetylation may also occur. These phase II reactions and
enzymes have not been widely studied with respect to pesticides.
Phosphate Conjugation
Phosphorylation is not a common reaction in xenobiotic metabolism and, to date, has
been described only in insects. The enzyme from the cockroach requires magnesium
and utilizes ATP. It is known to phosphorylate 1-naphthol, a metabolite of carbaryl,
and p -nitrophenol, a metabolite of parathion and methyl parathion.
SUMMARY AND CONCLUSIONS
Pesticides are subject to modification by a wide range of phase I and phase II enzymes
and their isoforms and polymorphic variants. The products are numerous and second-
ary modification of the primary metabolites complicates the situation further. Since
the products may be more (activation) or less (detoxication) toxic than the parent
chemical, knowledge of metabolism may be critical in the extrapolation from experi-
mental animal to humans necessary for accurate human health risk assessment.
REFERENCES
Adams, N. H., Levi, P. E., & Hodgson, E. (1990). In vitro studies of the metabolism of atrazine, simazine and
terbutryn in several vertebrate species. J. Agric. Food Chem. , 28 , 1411-1417.
Arand, M., Cronin, A., Adamska, M., & Oesch, F. (2005). Epoxide hydrolases: Structure, function, metabo-
lism and assay. Methods Enzymol. , 400 , 569-588.
Bell, D. A., Thompson, C. L., Taylor, J., Miller, C. R., Perera, F., Hsieh, L. L., et al. (1992). Genetic monitor-
ing of human polymorphic cancer susceptibility genes by polymerase chain reaction: Application to
glutathione transferase μ. Environ. Health Perspect. , 98 , 113.
Bogaards, J. J. P., van Ommen, B., Wolf, C. R., & van Bladeren, P. J. (1995). Human cytochrome P450
enzyme selectivities in the oxidation of chlorinated benzenes. Toxicol. Appl. Pharmacol. , 132 , 44-52.
Butler, A. M., & Murray, M. (1997). Biotransformation of parathion in human liver: Participation of
CYP3A4 and its inactivation during microsomal parathion oxidation. J. Pharmacol. Exp. Ther. , 280 ,
966-973.
Chambers, J. E., & Carr, R. L. (1995). Biochemical mechanisms contributing to species differences in
insecticidal toxicity. Toxicology , 105 , 291-304.
Cherrington, N. J., Can, Y., Cherrington, J. W., Rose, R. L., & Hodgson, E. (1998). Physiological factors
affecting protein expression of flavin-containing monooxygenases 1, 3 and 5. Xenobiotica , 7 , 673-682.