Factors Determining the Toxicity of Organic Pollutants to Animals and Plants - Organic Pollutants: An Ecotoxicological Perspective - page 32

taBLe 2.3
types of carboxylesterase Isolated from rat Liver microsomes

genetic
classification PI Value Substrates comments

5.6 ES3 Simple aromatic esters, acetanilide,

lysophospholipids, monoglycerides,
long-chain acyl carnitines

Sometimes called
lysophospholipase to
distinguish it from other
esterases of this kind

6.2/6.4 ES4 Aspirin, malathion, pyrethroids,

palmitoyl CoA, monoacylglycerol,
cholesterol esters

May correspond to EC 3.1.2.2
and EC 3.1.1.23

6.0 ES8/ES10 Short-chain aliphatic esters,

medium-chain acylglycerols,
clofibrate, procaine

ES8 may be a monomer, ES10
a dimer

5.0/5.2 ES15 Mono- and diacylglycerols, acetyl

carnitine, phorbol diesters

Corresponds to acetyl carnitine
hydrolase

Source: Data from Mentlein et al. 1987.

endogenous and exogenous. Structural models indicate a highly unrestricted active
site, in keeping with this characteristic (Lewis 1996). This is in marked contrast to
the highly restricted active sites proposed for family CYP1A. Although CYP4 is espe-
cially involved in the endogenous metabolism of fatty acids, it does have a key role in
the metabolism of a few xenobiotics, including phthalate esters.
Cytochrome P450 metabolism of xenobiotics has been less well studied in inverte-
brates compared to vertebrates. The importance of this subject in human toxicology
has been a powerful stimulus for work on vertebrates, but there has been no compa-
rable driving force in the case of invertebrate toxicology. Also, in the earlier stages of
this work, there were considerable technical problems in isolating and characterizing
the P450s of invertebrates, associated in part with the small size of many of them and
also the instability of subcellular preparations made from them. Insects, however, have
received more attention than other invertebrate groups, partly because of the impor-
tance of the use of insecticides for the control of major pest species and vectors of
disease (e.g., malarial mosquito and tse-tse flies). In insects, P450s belonging to gene
family CYP6 have been shown to have an important role in xenobiotic metabolism.
CYP6D1 of the housefly ( Musca domestica ) has been found to hydroxylate cyper-
methrin and thereby provide a resistance mechanism to this compound and other
pyrethroids in this species (Scott et al. 1998; see also Chapter 12). Also, this insect
P450 can metabolize plant toxins such as the linear furanocoumarins xanthotoxin
and bergapten (Ma et al. 1994). This metabolic capability has been found in the lepi-
dopteran Papilio polyxenes (black swallowtail), a species that feeds almost exclu-
sively on plants containing furanocoumarins.
The classification of P450s, which is based on amino acid sequencing, bears some
relationship to metabolic function. That said, some xenobiotic molecules, especially