• Once digestion reaches the duodenum, there is bile coming in alongside pancreatic juices
• Bile contains bicarbonate, which raises pH of food in the gut
• The duodenum is a different place, first part of the small intestine
• Pancreatic juices also have proteolyses - they are activated once they get to the duodenum
• Bile contains bicarbonate and raises pH of food in the gut

Zymogen -> Active Enzyme
- Chymotrypsinogen -> Chymotrypsin
- Trypsinogen -> Trypsin
- Procarboxypeptidase ->Carboxypeptidase
- Proelastase -> Elastase

• Pepsin becomes deactivated - does not do well in a high pH environment

• Good for proteases from pancreas - won’t be randomly cleaved

• Once the pancreatic zymogens get to the small intestine, they becomes proteolysed

• The pancreatic zymogens have left the duodenum

• Enzyme: Enteropeptidase

• Found on surface of small intestine cells

• Transmembrane protein - activity extends into lumen of small intestine

• Zymogens become active enzymes (come from pancreas)

• Trypsinogen encounters enteropeptidase, which cleaves off inhibitory portions of trypsinogen to make it into trypsin

• This works like a cascade, as zymogens become activated they activate surrounding zymogens

• Trypsin will activate all the zymogen that come in from the pancreas

• Why is it stored as inactive? Because the active trypsin would damage the pancreas, where trypsinogen comes from

• Possesses proteolytic activity to activate itself -> trypsinogen autoactivation

• These proteolyses are highly specific and cleave at specific amino acid sequences Active site specificity

Ex. Tryptin has an Asp in its active site -> specific for positive amino acids -> cleaves after large hydrophobic amino acids

• Positive side chains likes negative side chains (Arginine likes Asp)
• Hydrophobic side chains (Val) will not cleave after a positive side chain
• Trypsin: has a negatively charged amino acid, aspartate, in its active site.
• Cleaves after positively charged amino acids like lysine and arginine.
• Chymotrypsin: has a large active site without any bulky hydrophobic residues, without any charged residues
• Cleaves after large hydrophobic amino acids like phenylalanine or tyrosine, or even tryptophan.
• Elastase: typically cleaves after an alanine or valine.
• Once the proteins are cleaved, they are taken up by the epithelial cells on the surface of the small intestine into the enterocytes
• Epithelial cells separate the inside of the body from the external environment
• Digestive tract is external environment
• Broken down even more by internal peptidases
• Shuttled in the bloodstream as amino acids