T. Satoh et M. Hosokawa, THE MAMMALIAN CARBOXYLESTERASES - FROM MOLECULES TO FUNCTIONS, Annual review of pharmacology and toxicology, 38, 1998, pp. 257-288
Multiple carboxylesterases (EC 3.1.1.1) play an important role in the
hydrolytic biotransformation of a vast number of structurally diverse
drugs. These enzymes are major determinants of the pharmacokinetic beh
avior of most therapeutic agents containing ester or amide bonds. Carb
oxylesterase activity can be influenced by interactions of a variety o
f compounds either directly or at the level of enzyme regulation. Sinc
e a significant number of drugs are metabolized by carboxylesterase, a
ltering the activity of this enzyme class has important clinical impli
cations. Drug elimination decreases and the incidence of drug-drug int
eractions increases when two or more drugs compete for hydrolysis by t
he same carboxylesterase isozyme. Exposure to environmental pollutants
or to lipophilic drugs can result in induction of carboxylesterase ac
tivity. Therefore, the use of drugs known to increase the microsomal e
xpression of a particular carboxylesterase, and thus to increase assoc
iated drug hydrolysis capacity in humans, requires caution. Mammalian
carboxylesterases represent a multigene family, the products of which
are localized in the endoplasmic reticulum of many tissues. A comparis
on of the nucleotide and amino acid sequence of the mammalian carboxyl
esterases shows that all forms expressed in the rat can be assigned to
one of three gene subfamilies with structural identities of more than
70% within each subfamily. Considerable confusion exists in the scien
tific community in regards to a systematic nomenclature and classifica
tion of mammalian carboxylesterase. Until recently, adequate sequence
information has not been available such that valid links among the mam
malian carboxylesterase gene family or evolutionary relationships coul
d be established. However, sufficient basic data are now available to
support such a novel classification system.