In vitro deacetylation studies with isomeric acetamidobiphenyls using selective carboxylesterase inhibitors.

The hydrolysis of three isomeric arylamides 2-acetamidobiphenyl (2-AABP), 3-acetamidobiphenyl (3-AABP) and 4-acetamidobiphenyl (4-AABP) by microsomal carboxylesterases from mouse, hamster, guinea-pig, rat and rabbit livers was investigated. 2-AABP was hydrolysed at the fastest rate in all species except the mouse, the rate of hydrolysis of the 3 and 4 isomers was similar. The hydrolysis of the isomers in all species was inhibited by 10(-4) M paraoxon permitting the general identification of enzyme(s) responsible as "B" esterases. The more selective inhibitors bis-(4-nitrophenyl) phosphate (BNPP) and bis-(4-cyanophenyl) phosphate (BCPP) permitted further characterisation of the esterase(s) as a ES-3 carboxylesterase. However, the hydrolysis of 2-AABP was considerably less sensitive to these inhibitors than 3-AABP and 4-AABP, indicating that 2-AABP is a favoured substrate for the enzyme. The mouse arylamide hydrolysing activity was uniformly less sensitive to both BNPP and BCPP suggesting an enzyme distinct from ES-3 carboxylesterase may be involved.