Abstract

Microsomal carboxylesterase activities in 12 human livers were determined using 10 kinds of carboxylesterase substrates (p-nitrophenylacetate, p-nitrophenylpropionate, p-nitrophenylbutyrate, butanilicaine, isocarboxazid, palmitoyl-coenzyme-A, malathion, clofibrate, acetanilide, and phenacetin). There were large individual differences in the 12 humans based on experimental results in the past several years in our laboratory. We found that all human liver microsomes have RH1-immunoreactive carboxylesterase, and the carboxylesterase content in liver also showed large individual differences. The RH1-immunoreactive carboxylesterase concentration correlated well with those of p-nitrophenylesters, clofibrate, butanilicaine, and isocarboxazid, and anti-RH1 immunoglobulin G strongly inhibited human liver hydrolase activity. These findings indicate that one major carboxylesterase isozyme that is immunoreactive with anti-RH1 in human liver microsomes has catalytic activity on major carboxylesterase substrates, and thus hydrolase activity in human liver depends on the expression level of this carboxylesterase isozyme. These observations should be useful in understanding the action of carboxylesterases on drug metabolism in humans.