Procarboxypeptidase

Procarboxypeptidase is the zymogen form of the pancreatic carboxypeptidase enzymes. In humans, the pancreas secretes procarboxypeptidase A and procarboxypeptidase B as part of pancreatic juice. These proenzymes are inactive precursors of zinc-dependent exopeptidases that remove amino acids from the C-terminus of peptide substrates during digestion.

Activation occurs in the small intestine. The protease trypsin, itself activated from trypsinogen by enteropeptidase in the duodenum, cleaves a short activation peptide from each procarboxypeptidase to yield the active enzymes carboxypeptidase A and carboxypeptidase B. This proteolytic activation prevents the enzymes from harming pancreatic tissue.

Active carboxypeptidase A has a preference for bulky hydrophobic C-terminal residues, while carboxypeptidase B preferentially cleaves basic residues such as lysine and arginine. Together, they function in the terminal step of protein digestion, acting after endopeptidases have cleaved proteins into smaller peptides.

Regulation occurs at the level of zymogen activation; premature activation within the pancreas is a feature of pancreatitis pathophysiology. Procarboxypeptidases thus exemplify digestive enzyme zymogens that ensure enzymes become active only where needed, in the intestinal lumen.