Proteolysis

Proteolysis is the biochemical process by which proteins are degraded into smaller peptides or amino acids through the hydrolysis of peptide bonds, catalyzed by proteases. It is a central mechanism in digestion, protein turnover, and the activation or inactivation of many functional protein precursors, including zymogens and peptide hormones. Proteolytic events can occur outside cells (extracellular) or inside cells (intracellular), and involve endopeptidases that cleave within the polypeptide chain as well as exopeptidases that remove terminal residues.

Major proteolytic systems include digestive proteases such as pepsin in the stomach and trypsin and chymotrypsin in the small intestine, along with pancreatic carboxypeptidases; intracellularly, the ubiquitin-proteasome system and lysosomal proteases such as cathepsins contribute to protein catabolism. Endoproteases and exopeptidases act in concert to produce peptides of varying lengths and to generate bioactive peptides from larger precursors.

Proteolysis is tightly regulated at multiple levels. Many proteases are synthesized as inactive zymogens and require cleavage for activation; proteolytic activity is constrained by cellular compartments, pH, and specific inhibitors such as serpins and metalloproteinase inhibitors (TIMPs).

Physiological roles include digestion, cell signaling, and quality control of proteins, while dysregulated proteolysis is linked to disease, such as cancer invasion driven by matrix metalloproteinases and neurodegenerative disorders associated with impaired proteostasis. Proteolysis therefore influences both normal biology and pathology by controlling protein function and turnover.