but the last two introns have the same position
[2, 44, 51]. G 1 AChEs and G2 AChEs are also
detectable in other insect species; the report in
1978 of an A form in Musca domestica probably
requires reexamination [12]. In contrast to other
esterases, there is no known polymorphism of the
Drosophila AChE; no electrophoretic variants
were found in studies of 25 populations of Drosophila melanogaster and 30 populations of D. pseudoobscura. The results of density gradient centrifugation suggest the existence of G 1, G2 and G4
forms of AChE in the ascidian Ciona intestinalis;
asymmetric forms, on the other hand, appear to
be absent. AChE aggregates 8S (450 kDa), lOS,
18S and 32S have been isolated from the trematode Schistosoma mansoni [165].
17.1.3 Lipases and Cholesterol Ester
Hydrolases
There are four lipolytic activities in mammalian
gnt: (1) the preduodenallipases or gastric lipases,
which are produced in glands beneath the tongue,
in the pharynx or in the stomach, depending upon
the species; (2) the colipase-dependent pancreas
lipase; (3) the bile salt-dependent lipases of the
pancreas and the milk; and (4) the phospholipase
Az, also from the pancreas.
The preduodenallipases of humans, rats, mice,
cattle and sheep are mainly produced in the
Ebner glands beneath the tongue, and those of
the guinea-pig, rabbit, dog, horse, and pig are
produced in the major cells of the stomach. They
are especially active in the stomach, where in
humans 30 % of triacylglycerols (TAGs) are
already cleaved. Their activity varies greatly with
the species [48, 104]. The rat and human lingual
lipases are glycoproteins with 377-379 amino
acids and show 78 % sequence agreement. The
enzyme acts as a typical lipase only on aggregated
substrates, but in contrast to pancreas lipase preferentially hydrolyses the sn-3 ester bond and
shows marked product inhibition; thus, TAG
cleavage only results in diacylglycerol (DAG).
The pH dependence is broad, with an optimum of
4.5, and it is quite possible that the enzyme functions at neutral pH in the small intestine. Whatever the case, the lingual lipases promote the
emulsification of fats in the small intestine; DAG
is produced and free fatty acids accumulate at the
fat-water interface [13, 48].
The classical pancreas lipase (EC 3.1.1.3) is
classified as bile salt-independent because it is
fully active in the absence of bile salts and is, in
17.1.3 Lipases and Cholesterol Ester Hydrolases
661
fact, inhibited by bile acids above their critical
micellar concentration of 0.03-0.07 %; it is stimulated by calcium ions. Human pancreas lipase
consists of 465 amino acids and shows 85 %
sequence agreement with the pig enzyme, and
70 % agreement with the dog enzyme [85]. Micellar TAGs are attacked by pancreas lipase only
after partial lipolysis by gastric lipase [13]. The
pH optimum is 9. The pancreas lipase shows
maximum activity when it is anchored by colipase
to the surface of lipid micelles. Colipase is present in the pancreatic secretion as an inactive proenzyme that is activated by the tryptic hydrolysis
of an Arg-Gly bond; in the process, an oligopeptide of four or five amino acids is cleaved off. The
heat- and acid-stable colipase has been reported
from vertebrates of all classes down to the common hagfish Myxine glutinosa; the complete
sequence is known for pig, horse and human colipase and the N-terminal sequence is known for
the enzyme from the chicken and the shark Acanthias vulgaris. The polypeptide is very conservative: the N-terminal sequences of shark and man
agree 57 %, and those of the shark and chicken
agree 64 %. Nevertheless, the heterogeneous system of human lipase and shark colipase is fivefold
less active than the human homologous system.
This is probably due to differences in the charge
of the colipase, which has a pI of 10.2 in the shark
compared with 5.8 in humans [85, 157].
The bile salt-dependent lipase of the pancreas
or cholesterol esterase is secreted as an inactive
monomer of 65 kDa; in the rat it is polymerized
to active hexamers by trihydroxy bile acids and to
higher aggregates by dihydroxy bile acids. The
porcine and human pro-enzymes are converted to
active dimers by the action of cholic acid. The
enzyme acts upon soluble esters, such as triacetyl
or tripropionyl glycerol, methylbutyrate or lysolecithin, but also upon insoluble esters of cholesterol and vitamins A, D and E in bile acid-stabilized
micelles; it has little activity against emulsified
fats [113]. Human and gorilla milk contain a
lipase that is activated by bile acids and is of critical importance for milk digestion in infants. It is
synthesized in the milk glands and makes up
about 1 % of the total protein of human milk. It is
apparently encoded by the same gene as the bile
salt-dependent lipase of the pancreas. The
sequence consists of 722 amino acids and is
homologous to other serine esterases [4, 113].
The milk enzyme is not present in other mammals
such as the cow, goat, pig, horse, rat or guineapig; nor is it present in rhesus monkeys, and it
was therefore considered to be a relatively recent
[2, 44, 51]. G 1 AChEs and G2 AChEs are also
detectable in other insect species; the report in
1978 of an A form in Musca domestica probably
requires reexamination [12]. In contrast to other
esterases, there is no known polymorphism of the
Drosophila AChE; no electrophoretic variants
were found in studies of 25 populations of Drosophila melanogaster and 30 populations of D. pseudoobscura. The results of density gradient centrifugation suggest the existence of G 1, G2 and G4
forms of AChE in the ascidian Ciona intestinalis;
asymmetric forms, on the other hand, appear to
be absent. AChE aggregates 8S (450 kDa), lOS,
18S and 32S have been isolated from the trematode Schistosoma mansoni [165].
17.1.3 Lipases and Cholesterol Ester
Hydrolases
There are four lipolytic activities in mammalian
gnt: (1) the preduodenallipases or gastric lipases,
which are produced in glands beneath the tongue,
in the pharynx or in the stomach, depending upon
the species; (2) the colipase-dependent pancreas
lipase; (3) the bile salt-dependent lipases of the
pancreas and the milk; and (4) the phospholipase
Az, also from the pancreas.
The preduodenallipases of humans, rats, mice,
cattle and sheep are mainly produced in the
Ebner glands beneath the tongue, and those of
the guinea-pig, rabbit, dog, horse, and pig are
produced in the major cells of the stomach. They
are especially active in the stomach, where in
humans 30 % of triacylglycerols (TAGs) are
already cleaved. Their activity varies greatly with
the species [48, 104]. The rat and human lingual
lipases are glycoproteins with 377-379 amino
acids and show 78 % sequence agreement. The
enzyme acts as a typical lipase only on aggregated
substrates, but in contrast to pancreas lipase preferentially hydrolyses the sn-3 ester bond and
shows marked product inhibition; thus, TAG
cleavage only results in diacylglycerol (DAG).
The pH dependence is broad, with an optimum of
4.5, and it is quite possible that the enzyme functions at neutral pH in the small intestine. Whatever the case, the lingual lipases promote the
emulsification of fats in the small intestine; DAG
is produced and free fatty acids accumulate at the
fat-water interface [13, 48].
The classical pancreas lipase (EC 3.1.1.3) is
classified as bile salt-independent because it is
fully active in the absence of bile salts and is, in
17.1.3 Lipases and Cholesterol Ester Hydrolases
661
fact, inhibited by bile acids above their critical
micellar concentration of 0.03-0.07 %; it is stimulated by calcium ions. Human pancreas lipase
consists of 465 amino acids and shows 85 %
sequence agreement with the pig enzyme, and
70 % agreement with the dog enzyme [85]. Micellar TAGs are attacked by pancreas lipase only
after partial lipolysis by gastric lipase [13]. The
pH optimum is 9. The pancreas lipase shows
maximum activity when it is anchored by colipase
to the surface of lipid micelles. Colipase is present in the pancreatic secretion as an inactive proenzyme that is activated by the tryptic hydrolysis
of an Arg-Gly bond; in the process, an oligopeptide of four or five amino acids is cleaved off. The
heat- and acid-stable colipase has been reported
from vertebrates of all classes down to the common hagfish Myxine glutinosa; the complete
sequence is known for pig, horse and human colipase and the N-terminal sequence is known for
the enzyme from the chicken and the shark Acanthias vulgaris. The polypeptide is very conservative: the N-terminal sequences of shark and man
agree 57 %, and those of the shark and chicken
agree 64 %. Nevertheless, the heterogeneous system of human lipase and shark colipase is fivefold
less active than the human homologous system.
This is probably due to differences in the charge
of the colipase, which has a pI of 10.2 in the shark
compared with 5.8 in humans [85, 157].
The bile salt-dependent lipase of the pancreas
or cholesterol esterase is secreted as an inactive
monomer of 65 kDa; in the rat it is polymerized
to active hexamers by trihydroxy bile acids and to
higher aggregates by dihydroxy bile acids. The
porcine and human pro-enzymes are converted to
active dimers by the action of cholic acid. The
enzyme acts upon soluble esters, such as triacetyl
or tripropionyl glycerol, methylbutyrate or lysolecithin, but also upon insoluble esters of cholesterol and vitamins A, D and E in bile acid-stabilized
micelles; it has little activity against emulsified
fats [113]. Human and gorilla milk contain a
lipase that is activated by bile acids and is of critical importance for milk digestion in infants. It is
synthesized in the milk glands and makes up
about 1 % of the total protein of human milk. It is
apparently encoded by the same gene as the bile
salt-dependent lipase of the pancreas. The
sequence consists of 722 amino acids and is
homologous to other serine esterases [4, 113].
The milk enzyme is not present in other mammals
such as the cow, goat, pig, horse, rat or guineapig; nor is it present in rhesus monkeys, and it
was therefore considered to be a relatively recent