- Aminopeptidases are a class of exopeptidase enzymes that selectively cleave amino acids from the N-terminus of proteins and peptides. These enzymes are essential for protein degradation, processing, and regulation, playing a critical role in digestion, cellular metabolism, and the activation or inactivation of bioactive peptides.
- By sequentially removing amino acids from the amino-terminal end, aminopeptidases contribute to the breakdown of dietary proteins, the turnover of intracellular proteins, and the maturation of peptide hormones. Their activity is dependent on metal cofactors, typically zinc or manganese, which stabilize the enzyme’s active site and facilitate catalysis.
- In addition to their role in protein catabolism, aminopeptidases are involved in key physiological processes such as immune response modulation, blood pressure regulation, and neuropeptide processing. For example, some aminopeptidases participate in antigen presentation by trimming peptides for major histocompatibility complex (MHC) class I molecules, influencing adaptive immunity. Others, like angiotensin-converting enzyme regulators, impact cardiovascular function by metabolizing vasoactive peptides. Dysregulation of aminopeptidase activity has been linked to various diseases, including cancer, hypertension, and neurodegenerative disorders, highlighting their potential as therapeutic targets.
- Aminopeptidases are found across all domains of life, from bacteria to humans, with varying substrate specificities. Well-studied examples include leucyl aminopeptidase (LAP), which preferentially cleaves N-terminal leucine residues, and membrane alanyl aminopeptidase (APN/CD13), associated with tumor progression and immune evasion. Due to their broad biological significance, these enzymes are also utilized in biotechnology and pharmaceutical research, particularly in drug development and industrial protein processing. Understanding their mechanisms and regulation continues to be an important area of study in biochemistry and medicine.
