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.
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Chelsea Department of Pharmacy, King's College, University of London, U.K.
Gorrod
J W
JW
D000611:Aminobiphenyl Compounds / Q000378:metabolism*; D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006224:Cricetinae; D029721:Drosophila Proteins; D006168:Guinea Pigs; D006868:Hydrolysis; D007700:Kinetics; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D009596:Nitrophenols / Q000494:pharmacology*; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D010261:Paraoxon / Q000494:pharmacology*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D013379:Substrate Specificity
D000611:Aminobiphenyl Compounds; D029721:Drosophila Proteins; D009596:Nitrophenols; D009943:Organophosphorus Compounds; C016268:bis(4-cyanophenyl)phosphate; C002887:bis(4-nitrophenyl)phosphate; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C469609:esterase-S, Drosophila; D010261:Paraoxon