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)