INTERINDIVIDUAL VARIATION IN CARBOXYLESTERASE LEVELS IN HUMAN LIVER-MICROSOMES

Microsomal carboxylesterase activities in 12 human livers were determi ned using 10 kinds of carboxylesterase substrates (p-nitrophenylacetat e, p-nitrophenylpropionate, p-nitrophenylbutyrate, butanilicaine, isoc arboxazid, palmitoyl-coenzyme-A, malathion, clofibrate, acetanilide, a nd phenacetin), There were large individual differences in the 12 huma ns based on experimental results in the past several years in our labo ratory, We found that all human liver microsomes have RH1-immunoreacti ve carboxylesterase, and the carboxylesterase content in liver also sh owed large individual differences, The RH1-immunoreactive carboxyleste rase concentration correlated well with those of p-nitrophenylesters, clofibrate, butanilicaine, and isocarboxazid, and anti-RH1 immunoglobu lin G strongly inhibited human liver hydrolase activity. These finding s indicate that one major carboxylesterase isozyme that is immunoreact ive with anti-RH1 in human liver microsomes has catalytic activity on major carboxylesterase substrates, and thus hydrolase activity in huma n liver depends on the expression level of this carboxylesterase isozy me. These observations should be useful in understanding the action of carboxylesterases on drug metabolism in humans.