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Digestive System Proteases
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Digestive System Proteases

Proteases/Peptidases
  • Proteases (aka peptidases) catalyze peptide bond cleavage via hydrolysis (addition of a H20).
Note that originally the term protease carried a slightly broader definition: any enzyme involved in protein degradation (and didn't specify the mechanism) whereas the term peptidase bore a narrower definition: an enzyme that performs peptide bond hydrolysis. But now we use these terms interchangeably.
  • Most digestive enzymes are synthesized as zymogens (in an inactive form) and are activated as needed by physiological conditions (such as pH), self-cleavage, or cleavage by other proteins.
Peptidase Classes
Peptidases divide into:
Endopeptidases
  • Act on interior (or deeply internal) peptide bonds (ie, in the middle of the peptide chain).
Exopeptidases
  • Cleave free N-terminal and C-terminal amino acids.
— Aminopeptidases are forms of exopeptidases that cleave single amino acids at the amino (N-terminal) end of the peptide chain — Carboxypeptidases are forms of exopeptidases that cleave single amino acids at the carboxy (C-terminal) end of the peptide chain.
Stomach Proteases
  • Pepsin (Endopeptidase)
    • The stomach secretes: pepsin, its zymogen is pepsinogen, it's most active in a highly acidic environment (pH ~ 1.5) but acts in the stomach where the pH is ~2 but has a range of 1.5 to 4.5.
Pancreatic Proteases
  • Trypsin (Endopeptidase)
    • Trypsin is secreted as trypsinogen.
    • It and the other pancreatic endopeptidases (listed next) are optimally active in a pH of 8 but act in the proximal small intestine lumen where the pH is ~6.
  • Chymotrypsin (Endopeptidase)
    • Chymotrypsin (which, notably, has a highly reactive serine residue), is secreted as chymotrypsinogen.
  • Elastase (Endopeptidase)
    • Elastase is secreted as proelastase.
  • Carboxypeptidases (Exopeptidase)
    • Carboxypeptidase A is secreted as procarboxypeptidase A.
    • It operates at an optimal pH of 9, but the intracellular cytoplasm of the enterocyte is ~ 7.
Small Intestine Peptidases
  • Aminopeptidases (Exopeptidase)
    • The small intestine releases aminopeptidases, which do not have a zymogen form, operate at in a similar pH profile as carboxypeptidases
  • Dipeptidase (Exopeptidase)

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