Clinical Biochemistry of Domestic Animals (Sixth Edition) - UMK ...

V. Exocrine Pancreatic Secretions
421
TABLE 14-4 Relationships among the Activities of
Pancreatic Endopeptidases and Exopeptidases
Enzyme Type Activity
Trypsin Endopeptidase Produces peptides
with C-terminal
basic amino acids
Carboxypeptidase B Exopeptidase Removes C-terminal
basic amino acids
Chymotrypsin Endopeptidase Produces peptides
with C-terminal
aromatic amino
acids
Elastase Endopeptidase Produces peptides
with C-terminal
nonpolar amino
acids
Carboxypeptidase A Exopeptidase Removes C-terminal
aromatic and
nonpolar amino
acids
The exopeptidases attack either the carboxy-terminal or
amino-terminal peptide bonds, releasing single amino
acids. The principal exopeptidases secreted by the pancreas
are carboxypeptidases A and B. The endopeptidases and
exopeptidases act in complementary fashion ( Table 14-4 ),
ultimately producing free amino acids or very small peptides.
The free amino acids are absorbed directly, and the
small peptides are further hydrolyzed by the aminopeptidases
of the intestinal mucosa.
The pancreatic peptidases are secreted as the inactive
proenzymes (zymogens), trypsinogen, chymotrypsinogen,
and the procarboxypeptidases A and B. Trypsinogen
is converted to active trypsin in two ways. At alkaline pH,
trypsinogen can be converted autocatalytically to trypsin.
The activated enzyme is then capable of converting more
zymogen to active enzyme. Trypsinogen also can be activated
by the enzyme enterokinase, which is produced by
duodenal mucosa. The latter reaction is highly specific in
that enterokinase will activate trypsinogen but not chymotrypsinogen.
Chymotrypsinogen, proelastase, and the
procarboxypeptidases A and B are converted to active
enzymes by the action of trypsin.
The amino acid sequences and other structural characteristics
of bovine trypsinogen and chymotrypsinogen
have been determined ( Brown and Hartley, 1966 ; Hartley
et al., 1965 ; Hartley and Kauffman, 1966 ). The polypeptide
chain of trypsinogen contains 229 amino acid residues.
Activation of trypsinogen occurs with hydrolysis of a single
peptide bond located in the 6 position between lysine and
isoleucine. As the C-terminal hexapeptide is released,
enzyme activity appears along with a helical structure of
the parent molecule. Chymotrypsinogen A is composed of
245 amino acid residues and has numerous structural similarities
to trypsinogen. Activation of the chymotrypsinogen
also occurs with cleavage of a single peptide bond.
4 . Lipase
The pancreas produces several lipolytic enzymes with different
substrate specificities. The most important of these
from a nutritional viewpoint is the lipase responsible for
hydrolysis of dietary triglyceride. This enzyme has the
unique property of requiring an oil-water interface for
activity so that only emulsions can be effectively attacked.
The principal products of lipolysis are glycerol, monoglycerides,
and fatty acids. The monoglycerides and fatty acids
accumulate at the oil-water interface and can inhibit lipase
activity. Transfer of these products from the interface to the
aqueous phase is favored by HCO 3
secreted by the pancreas
and by the bile salts.
Two other carboxylic ester hydrolases have been characterized
in pancreatic secretion. Both enzymes have an
absolute requirement for bile salts, in contrast to glycerol
ester hydrolase, which is actually inhibited by bile salts at
pH 8. One of the enzymes requiring bile salts is a sterol
ester hydrolase responsible for hydrolysis of cholesterol
esters, and the other enzyme hydrolyzes various watersoluble
esters. The pancreas also secretes phospholipase A,
which in the presence of bile converts lecithin to lysolecithin,
an effective detergent that contributes to the emulsification
of dietary fat.
B . Control of Pancreatic Secretions
1 . Hormonal Control
Pancreatic secretion is controlled and coordinated by both
neural and endocrine mechanisms. When ingesta or HCl
enters the duodenum, the hormone secretin, which is produced
by the duodenal mucosa, is released into the circulation.
Secretin increases the volume, pH, and HCO 3
concentration of the pancreatic secretion.
Secretin is a polypeptide hormone containing 27 amino
acid residues, and all 27 amino acids are required to maintain
the helical structure of the molecule and its activity
( Bodanszky et al., 1969 ). The C-terminal amide of secretin
is a property shared with other polypeptide hormones such
as gastrin and vasopressin, which act on the flow of water
in biological systems ( Mutt and Jorpes, 1967 ). In addition
to its effects on the pancreas, secretin also increases the
rate of bile formation.
The secretin-stimulated pancreatic juice has a large volume,
high HCO 3
concentration but a low enzyme activity.