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

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. Auto activation

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 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. Trypsinogen

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 lumen into intestinal mucosa (across 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 tri-peptides: 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.