endoproteolysis

Endoproteolysis refers to proteolytic cleavage at peptide bonds within a polypeptide chain, producing fragments of smaller polypeptides or mature proteins. It is distinguished from exoproteolysis, which removes amino acids from the ends of a peptide. Endoproteolysis is catalyzed by endoproteases or proteases that recognize internal sequence motifs and often act in a regulated, context-dependent manner.

Examples of endoproteases include digestive enzymes such as pepsin (an aspartic protease in the stomach) and the pancreatic serine proteases trypsin and chymotrypsin, as well as cysteine proteases like papain and various metalloproteases. Beyond digestion, endoproteolysis is central to post-translational processing: many proproteins and prohormones are activated by endoproteolytic cleavage to yield functional mature proteins, as seen in proinsulin processing to insulin and the activation of clotting factors by specific proteolytic steps.

Endoproteolysis also underpins intracellular protein turnover and signaling. In the ubiquitin–proteasome system, proteins are marked for degradation and cleaved into peptides by proteasomes, performing endoproteolysis within the cytosol and nucleus. Proteolytic cascades, such as those in coagulation and complement systems, rely on sequential endoproteolytic activations to amplify responses. Regulation occurs via substrate specificity, cellular localization, pH, cofactor requirements, and protease inhibitors that prevent unwanted cleavage.

Biological and medical relevance includes protein maturation, digestive physiology, and disease when dysregulated proteolysis contributes to neurodegeneration, cancer, inflammation, or coagulation disorders.