Because they also attack phospho ester bonds in
organophosphates such as paraoxon, they may
also be classified as phosphatases. The blood
plasma of many vertebrates also contains an acetyl esterase that is specific for the acetate residue
in the platelet-activating factor 1-alkyl-2-acetylsn-glycero-3-phosphocholine. This enzyme is
apparently present in all mammals but is missing
from birds (chicken, pigeon, turkey) and anurans
(Rana pipiens); it has been reported in the snake
Thamnophis sirtalis, the turtle Terrapene carolina
and the teleosts Salmo gairdneri and Lepomis
macrochirus. The action of the platelet-activating
factor has, as yet, been investigated only in mammals, and thus an explanation for the particularly
sporadic distribution of this enzyme is not available [21]. The insects have just as complicated a
spectrum of esterases as do the vertebrates. For
example, 18 esterases have been separated electrophoretically in the mosquito Culex tarsalis, of
which 14 can be classified as carboxyl esterases,
two as acetylcholinesterases and one each as an
aryl esterase and an acetyl esterase. Here again, it
is impossible to derive the biological importance
of these different enzymes. The aryl esterases
take part in the detoxification of the organophosphate insecticides and are apparently widespread in insects. Such an enzyme from the bug
Triatoma infestans is one of the few insect esterases so far subjected to purification attempts [92].
Quite understandable interest has been aroused
by the esterases that inactivate juveline hormones
by cleavage of the methyl group. The specific
juvenile hormone esterases are distinguishable
from non-specific esterases in that they are
not inhibited by DIPF but are inhibited by certain inhibitors which are only effective in this
case, e.g. EPPAT (O-ethyl-S-phenyl-phosphoamidothiolate). These enzymes have been discussed already in connection with the juvenile
hormones (p. 615). The insect esterases are model
examples of enzyme polymorphism. For this reason, two highly polymorphic esterases from Drosophila mojavensis have been isolated and studied
in detail. Esterase 4 is a dimer of 62- to 64-kDa
subunits with a-naphthylacetate as the optimal
substrate. The usual inhibitors are only effective
at very high concentrations (DIPF, eserine) or are
only very weak (PCMB); thus, the enzyme is
classifiable as an acetyl esterase (EC 3.1.1.6).
Esterases 4 and 5 differ in only 6 of their 34 Nterminal amino acids, and are apparently products of duplicated genes, such as are found in
other Drosophila species, but which are expressed in a species-, stage- or organ-specific manner
17.1.2 Cholinesterases
659
[122]. A carboxyl esterase isolated from Caenorhabditis elegans shows significant similarity, at
least in the 13 N-terminal amino acids, to the latter two enzymes from Drosophila mojavensis
[98].
17.1.2 Cholinesterases
Essential components of the cholinergic synapses
of probably all metazoans are enzymes that can
hydrolase acetylcholine. It is not clear, however,
whether these enzymes are comparable with the
cholinesterases of the vertebrates, and they are
characterized in particular by specific inhibition
by eserine. Two types of cholinesterase can be distinguished in the vertebrates. The acetylcholinesterase (EC 3.1.1.7, AChE) of cholinergic synapses is well known for its extremely high turnover
rate of 15000 S-I. In addition, many cells contain
an enzyme that cleaves many other choline esters
in addition to acetylcholine; this is known as
butyrylcholinesterase (BChE) or pseudocholinesterase (EC 3.1.1.8). A clear differentiation
between AChE and BChE is only really possible
in the higher vertebrates; in lower vertebrates
and invertebrates the association of acetylcholine-cleaving activity with one or other of the
two types is not always possible. For example,
the BChE from the heart of the electric ray Torpedo sp. is responsible for the physiological inactivation of the transmitter in the heart, and this
enzyme hydrolyses acetylcholine better than
butyrylcholine. The cholinesterases from the
muscles of the flounder Pleuronectes flesus and
the enzyme designated as an acetylcholinesterase
in Drosophila lie between AChE and BChE in
their specificities [26, 158]. AChE and BChE are
glycoproteins with a high degree of heterogeneity
between tissues in their quaternary structure,
charge and carbohydrate composition. In the vertebrates, they are found particularly in the nervous system and muscle, but also occur in erythrocytes and other cells, in blood plasma and egg
yolk, where their function is completely unknown. The muscle-derived electric organs of the
electric eel Electrophorus electric us and the electric rays Torpedo californica, T. marmorata and
Narce japonica are especially rich in AChEs
[166].
AChEs and BChEs exist in multiple molecular
forms. The asymmetrical forms A4, A8 and A12
are made up of one, two or three catalytic tetramers bound to a triple-helical, collagen-like tail
unit (Fig. 17.1). This tail unit contains hydroxy-
organophosphates such as paraoxon, they may
also be classified as phosphatases. The blood
plasma of many vertebrates also contains an acetyl esterase that is specific for the acetate residue
in the platelet-activating factor 1-alkyl-2-acetylsn-glycero-3-phosphocholine. This enzyme is
apparently present in all mammals but is missing
from birds (chicken, pigeon, turkey) and anurans
(Rana pipiens); it has been reported in the snake
Thamnophis sirtalis, the turtle Terrapene carolina
and the teleosts Salmo gairdneri and Lepomis
macrochirus. The action of the platelet-activating
factor has, as yet, been investigated only in mammals, and thus an explanation for the particularly
sporadic distribution of this enzyme is not available [21]. The insects have just as complicated a
spectrum of esterases as do the vertebrates. For
example, 18 esterases have been separated electrophoretically in the mosquito Culex tarsalis, of
which 14 can be classified as carboxyl esterases,
two as acetylcholinesterases and one each as an
aryl esterase and an acetyl esterase. Here again, it
is impossible to derive the biological importance
of these different enzymes. The aryl esterases
take part in the detoxification of the organophosphate insecticides and are apparently widespread in insects. Such an enzyme from the bug
Triatoma infestans is one of the few insect esterases so far subjected to purification attempts [92].
Quite understandable interest has been aroused
by the esterases that inactivate juveline hormones
by cleavage of the methyl group. The specific
juvenile hormone esterases are distinguishable
from non-specific esterases in that they are
not inhibited by DIPF but are inhibited by certain inhibitors which are only effective in this
case, e.g. EPPAT (O-ethyl-S-phenyl-phosphoamidothiolate). These enzymes have been discussed already in connection with the juvenile
hormones (p. 615). The insect esterases are model
examples of enzyme polymorphism. For this reason, two highly polymorphic esterases from Drosophila mojavensis have been isolated and studied
in detail. Esterase 4 is a dimer of 62- to 64-kDa
subunits with a-naphthylacetate as the optimal
substrate. The usual inhibitors are only effective
at very high concentrations (DIPF, eserine) or are
only very weak (PCMB); thus, the enzyme is
classifiable as an acetyl esterase (EC 3.1.1.6).
Esterases 4 and 5 differ in only 6 of their 34 Nterminal amino acids, and are apparently products of duplicated genes, such as are found in
other Drosophila species, but which are expressed in a species-, stage- or organ-specific manner
17.1.2 Cholinesterases
659
[122]. A carboxyl esterase isolated from Caenorhabditis elegans shows significant similarity, at
least in the 13 N-terminal amino acids, to the latter two enzymes from Drosophila mojavensis
[98].
17.1.2 Cholinesterases
Essential components of the cholinergic synapses
of probably all metazoans are enzymes that can
hydrolase acetylcholine. It is not clear, however,
whether these enzymes are comparable with the
cholinesterases of the vertebrates, and they are
characterized in particular by specific inhibition
by eserine. Two types of cholinesterase can be distinguished in the vertebrates. The acetylcholinesterase (EC 3.1.1.7, AChE) of cholinergic synapses is well known for its extremely high turnover
rate of 15000 S-I. In addition, many cells contain
an enzyme that cleaves many other choline esters
in addition to acetylcholine; this is known as
butyrylcholinesterase (BChE) or pseudocholinesterase (EC 3.1.1.8). A clear differentiation
between AChE and BChE is only really possible
in the higher vertebrates; in lower vertebrates
and invertebrates the association of acetylcholine-cleaving activity with one or other of the
two types is not always possible. For example,
the BChE from the heart of the electric ray Torpedo sp. is responsible for the physiological inactivation of the transmitter in the heart, and this
enzyme hydrolyses acetylcholine better than
butyrylcholine. The cholinesterases from the
muscles of the flounder Pleuronectes flesus and
the enzyme designated as an acetylcholinesterase
in Drosophila lie between AChE and BChE in
their specificities [26, 158]. AChE and BChE are
glycoproteins with a high degree of heterogeneity
between tissues in their quaternary structure,
charge and carbohydrate composition. In the vertebrates, they are found particularly in the nervous system and muscle, but also occur in erythrocytes and other cells, in blood plasma and egg
yolk, where their function is completely unknown. The muscle-derived electric organs of the
electric eel Electrophorus electric us and the electric rays Torpedo californica, T. marmorata and
Narce japonica are especially rich in AChEs
[166].
AChEs and BChEs exist in multiple molecular
forms. The asymmetrical forms A4, A8 and A12
are made up of one, two or three catalytic tetramers bound to a triple-helical, collagen-like tail
unit (Fig. 17.1). This tail unit contains hydroxy-