Carboxypeptidases

Carboxypeptidases are exopeptidases that cleave amino acids one at a time from the carboxyl terminus of peptide substrates. They function as zinc-dependent metallo­peptidases of the M14 family in many organisms, and in mammals many forms are secreted digestive enzymes that are synthesized as inactive zymogens and activated in the small intestine. Other carboxypeptidases reside intracellularly or in microbes, plants, and insects, reflecting a diversity of physiological roles.

The catalytic mechanism typically centers on a zinc ion at the active site, coordinated by conserved residues, which helps activate a water molecule to attack the terminal peptide bond. Substrate specificity varies among family members: pancreatic carboxypeptidase A preferentially removes bulky hydrophobic C-terminal residues, while carboxypeptidase B favors basic residues; other enzymes have broader or distinct preferences. In addition to metallopeptidases, some organisms express serine carboxypeptidases that use a serine-based catalytic mechanism to accomplish C-terminal cleavage.

In humans, pancreatic carboxypeptidases A1 and A2 participate in dietary protein digestion, and other members such as carboxypeptidases in secretory pathways participate in processing peptide hormones and neuropeptides. Beyond mammals, carboxypeptidases in yeast, plants, and microbes contribute to protein turnover, maturation of signaling peptides, and other cellular processes.

Clinically, deficiencies or dysfunctions affecting carboxypeptidase activity can impact protein digestion and nutrient absorption, such as in pancreatic insufficiency. Carboxypeptidases also have utility in research and industry for generating C-terminally truncated peptides and for studying peptide processing and maturation.