AMINOPEPTIDASE INHIBITORS

AMINOPEPTIDASE INHIBITORS act on enzymes that cleave the N-terminal residue from oligopeptides or from proteins. They can be divided into classes on the basis of their functional characteristics. These classes are dealt with separately in terms of their alternate names, notable substrates and inhibitors. A number of these enzymes may be inhibited to enhance the action of endogenous peptides, though in most cases this has been achieved only experimentally. However, there is therapeutic interest in potentiating or enhancing some aspects of the action of mediator peptides, though often inhibition of more than one type of peptidase is necessary. For instance, inhibition of degradation of enkephalin has been shown to be analgesic, though inhibition of both aminopeptidase N and neutral endopeptidase is required in order to be effective.

Aminopeptidase N (EC 3.4.11.2; aminopeptidase M; CD 13) is a zinc-metalloproteinase located in the plasma membrane. Notable neuropeptide substrates include; leu-enkephalin, met-enkephalin, β-endorphin and Ύ-endorphin. Inhibitors include amastatin and actinonin.

Aminopeptidase A (EC 3.4.11.7; aspartate aminopeptidase; glutamyl aminopeptidase; BPI/6C3 antigen) is a Ca²⁺-activated zinc-metalloproteinase, which is located in the plasma membrane. Notable neuropeptide substrates include: angiotensin I, angiotensin II and met-enkephalin. Inhibitors include amastatin.

Aminopeptidase B (EC 3.4.11.6; aminopeptidase M1) is thought to be a chloride-activated-thiolproteinase. Substrates of interest include leu-enkephalin, met-enkephalin and bradykinin. Inhibitors include arphamenine A and arphamenine B.

Aminopeptidase P (EC 3.4.11.9; prolyl aminopeptidase) is located in the plasma membrane and is a zinc-metalloproteinase. Notable neuropeptide substrates include: bradykinin, substance P, neuropeptide Y, peptide YY and enterostatin. Inhibitors include apstatin.

Dipeptidylpeptidase IV (EC 3.4.11.5; postproline dipeptidyl aminopeptidase; CD26) is a serine protease located in the plasma membrane. Notable neuropeptide substrates include: substance P, neuropeptide Y, peptide YY and enterostatin. Inhibitors include diprotin A (Ile-Pro-Ile) and diprotin B (Val-Pro-Leu)

Pyroglutamyl aminopeptidase II (TRH degrading hormone) is a zinc-metalloproteinase, located in the plasma membrane. Notable neuropeptide substrates include thyrotrophin-releasing factor. There is no specific inhibitor.