exopeptidase

Exopeptidases are a class of peptidases that catalyze the hydrolysis of peptide bonds at the ends of peptide chains, releasing amino acids or dipeptides from substrates. This activity contrasts with endopeptidases, which cleave internal peptide bonds within a polypeptide. Exopeptidases are typically grouped by which terminus they act on: aminopeptidases remove residues from the N-terminus, carboxypeptidases remove residues from the C-terminus, and dipeptidyl peptidases release dipeptides from the N-terminus of peptides.

Most exopeptidases operate as zinc metalloproteases or serine proteases, and they may be soluble enzymes, secreted into digestive fluids, or bound to cell membranes or organelle surfaces. In digestion, exopeptidases trim peptide fragments produced by endoproteolysis to yield absorbable amino acids and small peptides. In cells, they contribute to peptide turnover, maturation, and antigen processing by generating appropriate fragments for presentation by MHC molecules.

Prominent examples include aminopeptidase N (APN, CD13), a zinc metalloprotease located on the surface of many cell types; pancreatic carboxypeptidases A and B, which remove C-terminal residues during digestion; and dipeptidyl peptidase-4 (DPP-4), a serine protease that releases N-terminal dipeptides and is a drug target in type 2 diabetes. Angiotensin-converting enzyme (ACE) is another exopeptidase that removes dipeptides from peptide substrates, notably in blood pressure regulation.

Understanding exopeptidases clarifies their roles in digestion, metabolism, immune function, and disease, as well as their utility as therapeutic targets.