aminopeptidases

Aminopeptidases are exopeptidases that catalyze the removal of amino acids from the N-terminus of peptide chains. By cleaving one amino acid at a time, they generate progressively shorter peptides and free amino acids. They function in a range of cellular compartments and organisms, and their activity complements endopeptidases that cut within peptide chains. Many aminopeptidases are zinc-dependent metalloproteases, but enzymes with other catalytic types also exist.

These enzymes exist as membrane-bound and soluble forms and have diverse tissue distributions. Notable examples include aminopeptidase N (APN, also known as CD13), a membrane-associated zinc metallopeptidase expressed in intestinal and other tissues; aminopeptidase P, with broad substrate specificity; leucine aminopeptidase (LAP). In the secretory pathway and cytosol are aminopeptidase ERAP1 and ERAP2, which trim antigenic peptides in the endoplasmic reticulum for loading onto MHC class I molecules.

Substrate preferences vary; some are relatively specific for N-terminal proline, leucine, or methionine, while others show broad specificity. Functionally, aminopeptidases participate in dietary protein digestion, peptide hormone inactivation, peptide turnover, and antigen processing. They also influence peptide signaling by controlling the abundance and length of bioactive peptides.

In medicine, aminopeptidases are targets for therapeutic intervention in cancer, infectious disease, and autoimmune conditions. Inhibitors such as bestatin (ubenimex) illustrate pharmacologic modulation of aminopeptidase activity. Research continues to clarify the roles of specific aminopeptidases in immunity and pathology, including the role of ERAPs in antigen presentation and tumor immune surveillance.