exopeptidases

Exopeptidases are proteolytic enzymes that cleave single amino acids from the termini of peptide chains. They differ from endopeptidases, which break peptide bonds within the chain. By removing residues from either the N-terminus or the C-terminus, exopeptidases help convert oligopeptides into free amino acids that can be absorbed or reused by cells.

Two principal classes are aminopeptidases, which remove amino acids from the N-terminus, and carboxypeptidases, which remove amino acids from the C-terminus. A subset known as dipeptidyl peptidases cleave dipeptides from the N-terminus, often with proline-directed specificity. Exopeptidases may be soluble enzymes or membrane-associated, and they include metallopeptidases, serine proteases, and other mechanistic types.

Many exopeptidases are found in the digestive system, such as pancreatic and brush-border enzymes that finish protein digestion in the small intestine. Others operate intracellularly in lysosomes, cytosol, or mitochondria, contributing to protein turnover, peptide trimming for antigen processing, or regulation of hormone activity by removing terminal residues.

Pharmacological relevance includes dipeptidyl peptidase-4 (DPP-4) inhibitors used to treat type 2 diabetes, which prolong activity of incretin hormones by blocking removal of N-terminal dipeptides. Defects or altered activity of exopeptidases can influence digestion, immune function, and peptide signaling.

Overall, exopeptidases play essential roles in protein processing and the generation of bioactive peptides, complementing endopeptidase action in proteostasis.