Esterases permethrins

The metabolism of permethrin will be taken more generally as an example of the metabolism of pyrethroids (Figure 12.2). The two types of primary metabolic attack are by microsomal monooxygenases and esterases. Monooxygenase attack involves... 

It was reported that the distribution and activities of esterases that catalyze pyrethroid metabolism using several human and rat tissues, including small intestine, liver, and serum, were examined [30]. The major esterase in human intestine was hCE2. //c/n.v-Permethrin was effectively hydrolyzed by pooled human intestinal microsomes (five individuals), while deltamethrin and bioresmethrin were not. This result correlated well with the substrate specificity of recombinant hCE2. In contrast, pooled rat intestinal microsomes (five animals) hydrolyzed trans-permethrin 4.5 times slower than the human intestinal microsomes. Furthermore, pooled samples of cytosol from human or rat liver were ca. half as hydrolytically active as the corresponding microsome fraction toward pyrethroids however, the cytosolic fractions had significant amounts (ca. 40%) of the total hydrolytic activity. Moreover, a sixfold interindividual variation in hCEl protein expression in human hepatic cytosols was observed. 

Both /nmv-permethrin and bioresmethrin were effectively cleaved by rat serum CES on the other hand, deltamethrin, esfenvalerate, a-cypermethrin, and cis-permethrin were slowly hydrolyzed. These results suggest that PBPK models of some pyrethroids may require the parameter of esterase activity to calculate the concentrations in the intestinal tract, liver, and serum if it is shown that the compounds in the model are appreciably hydrolyzed within these tissues. Such data for human and animal tissues will help to improve the accuracy of extrapolation between species (e.g., rats to humans) and thus enable better predictions of tissue and blood concentrations in humans following exposure to pyrethroids [30]. 

Many investigations of relevant enzymes in transformation of xenobiotics by aquatic species have shown that the similar enzymes observed in metabolism in soil, plant, and mammals play a role, such as esterases and oxidases [10, 159, 160]. Metabolism of pyrethroids has been most extensively studied in fish for cypermethrin (5) and permethrin (15). Aromatic hydroxylation at the 4 -position of the 3-phenoxybenzyl moiety followed by conjugation with glucuronic acid... 

Figure 8.28 Metabolic pathways of trans-permethrin in animals, a-d indicate oxidative metabolic sites. The white arrow indicates esterase action. (From Matsu mu ra, F., Toxicology of Insecticides, 2nd ed., Plenum Press, New York, 1985. With permission.)...

Yu, S.J., Liquid chromatographic determination of permethrin esterase activity in six phytophagous and entomophagous insects, Pestic. Biochem. Physiol, 36, 231,1990. 

Further studies following the same approach were carried out with Biaueiia genmnica, the German cockroach, L meda et al. (1988) compared the use of PBO, an oxidative inhibitor, with that of NIA 16288, both an oxidase and esterase inhibitor. The latter svnergized permethrin in this case, while the former had little effect. 

Derivatives of chrysanthemic acid such as (H ,3f )-permethrinic acid 143 are in demand for the manufacture of highly specific insecticides that do not persist in the environment. Mixtures of the esters 142 are easy to make and contain various proportions of the cis and trans diastereoisomers. Pig liver esterase accepts only the trans esters as substrates so complete hydrolysis gives the unchanged cis esters and hydrolysed but poorly resolved trans acids. At 50% conversion, kinetic resolution of the trans esters occurs.36... 

Organophosphate resistance in M. persicae is due to the production of large amounts of carboxylesterase E4 that degrade as well as sequester these insecticides (12). This is believed to be the only biochemical resistance mechanism in this species in many countries, including the UK., continental Europe, Japan, and Australia (25.). E4 additionally confers low levels of resistance to carbamates and to (IS)-trans-permethrin (12). This esterase has been characterized extensively by toxicological, biochemical, immunological and molecular studies (2, 22, 22f 22, 22) ... 

The relative levels of hCE-1 protein were measured in human microsomes by immunoblotting to determine if variation in hydrolytic metabolism was related to the abundance of hCE-1 in the microsomes. Human CE-1 levels did not correlate (r = 0.294) well with F ,ax values for the hydrolysis of Irans-permethrin. Esterases other than hCE-1 are believed to be responsible for the different values. CDMB (1,2-ethanedione, l-(2-chlorophenyl)-2-(3,4-dimethoxyphenyl)-(CAS no. 56159-70-7)) was used to inhibit the activity of hCE-2 (Wadkins et al. 2005). 

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