- Exopeptidases are a class of proteolytic enzymes that catalyze the hydrolysis of peptide bonds at the terminal ends of polypeptide chains.Â
- Unlike endopeptidases, which cleave internal peptide bonds within proteins or peptides, exopeptidases act on the N-terminal (aminopeptidases) or C-terminal (carboxypeptidases) residues, sequentially removing single amino acids or small peptides from the ends of a protein chain. This terminal activity plays essential roles in protein maturation, degradation, and nutrient digestion.
- Exopeptidases are broadly divided into two categories:
- Aminopeptidases, which cleave amino acids from the N-terminus of proteins or peptides.
- Carboxypeptidases, which cleave amino acids from the C-terminus.
- These enzymes function in many biological processes. In digestion, for example, exopeptidases such as aminopeptidase N and carboxypeptidase A further process the peptide fragments generated by endopeptidases like trypsin and pepsin, producing free amino acids for absorption in the intestine. In the cellular environment, exopeptidases participate in protein quality control and antigen processing—for instance, trimming peptides for loading onto MHC class I molecules during immune surveillance.
- The activity of exopeptidases is tightly regulated by pH, substrate specificity, and the presence of endogenous inhibitors. Like endopeptidases, exopeptidases are classified based on their catalytic mechanisms into metallo, serine, cysteine, and aspartic proteases. For example, carboxypeptidase A is a zinc metalloprotease, while aminopeptidase N also relies on zinc for its enzymatic function.
- Dysregulation of exopeptidase activity has been implicated in various diseases. For instance, abnormal aminopeptidase expression has been associated with cancer progression and metastasis, while defects in certain exopeptidases contribute to metabolic and neurological disorders. As such, exopeptidases are not only key to understanding proteolytic pathways but also serve as potential biomarkers and therapeutic targets.
- In summary, exopeptidases are essential for the controlled degradation and processing of proteins, acting at the terminal ends of peptide chains. Their function complements that of endopeptidases, together ensuring precise control over proteolysis in both physiological and pathological contexts.
