Protein digestion
Peptidases are enzymes responsible for protein digestion
Types of peptidases:
Endopeptidases: e.g. pepsin, trypsin, chymotrypsin and elastases
They cleave internal peptide bonds
Exopeptidases: cleave one amino acid either from carboxy (COOH)
terminal and so called Carboxypeptidases (A and B) or from amino
terminal and so called Aminopeptidases.
Protein digestion occur in stomach and intestine
A) Digestion in stomach:
The digestion of proteins begins in the stomach. passage of food into
stomach stimulates gastric mucosa to secret a polypeptide hormone
called: Gastrin which has the following actions:
1- stimulate the chief cells of gastric mucosa to secret the inactive
zymogen “pepsinogen”
2- stimulates the parietal cells of gastric mucosa to secret HCl which
activates pepsinogen into pepsin which activates more
pepsinogen”autoactivation”
 Pepsin is an acid stable endopeptidase, partially hydrolyse the
ingested proteins into large polypeptides and few amino acids.
HCl
Pepsin
Pepsinogen
Auto activation
pepsin
Pepsinogen
Pepsin
B) Digestion in small intestine
1-Action of pancreatic enzymes
Pancreas secret several proenzymes into duodenum. The release and
activation of pancreatic zymogens is mediated by the secretion of
cholecystokinine and secretin (GIT hormones).
Activation of pancreatic zymogens:
 The pancreatic zymogens are: trypsinogen, chymotrypsinogen
and pro-carboxypeptidases (A and B) and proteases.
 Enteropeptidase (formerly called enterokinase, synthesized from
intestinal mucosa) converts trypsinogen into active trypsin
 Trypsin activates more trypsinogen into trypsin
 Ttrypsin is the common activator of all the pancreatic
zymogens i.e activates chymotrypsinogen into chymotrypsin and
pro-carboxypeptidase into carboxypeptidase and proteases into
elastase.
enteropeptidase
Trypsinogen
trypsin
trypsin
Trypsinogen
trypsin
Chymotrypsinogen
trypsin
chymotrypsin
2- Intestinal peptidases: Aminopeptidases are intestinal enzymes
(membarne bound) and located on brush border.
 The endopeptidases (trypsin, chymotrypsin, elastases) cleaves
the large peptides(produced by pepsin) into small peptides.
 Carboxypeptidases and aminopeptidases hydrolyze the small
peptides into dipeptides, tripeptidesand free amino acids which
are the final products of the digestion
Specificity of peptidases:
Each of these enzymes has a different
specificity for the amino acids R groups
adjacent to the susceptible peptide
bond
Examples:
• Carboxypeptidase A breaks peptide
bond to liberate branched chain amino
acids (valine, leucine, isoleucine)
• Carboxypeptidase B breaks peptide bond
to liberate basic amino acids (arginine,
lysine)
•
Trypsin cleaves only when the carbonyl
group of the peptide bond is
contributed by arginine or lysine
Overview of protein digestion
Absorption of amino acids di-, and tri-peptides
Absorption of free amino acids
Free amino acids are absorbed
from
intestinal
intestinal
mucosa
lumen
(across
into
the
enterocyte membrane) by specific
Na+-dependant active transporters
showing mechanisms which are
similar to glucose transport
- The Na+ dependant amino acid transporters are located at the
brush- border membrane
- This is an indirect active process
- There is at least 5 specific transporters have been identified
Absorption of di- and tripeptides:
 Di- and tri-peptides are
absorbed
across
the
enterocyte membrane by H+dependent
transporters
(unlike glucose).
 Di- and tri-peptides are
further hydrolyzed to amino
acids inside the intestinal
mucosa.
 The final transfer of amino
acids
into
blood
by
facilitated diffusion
 So, Only free amino acids
appear in blood.