Acylpeptide hydrolase (APEH) (APEH)

Acylpeptide hydrolase (APEH) is a cytosolic homotetrameric serine protease belonging to the S9 family of prolyl oligopeptidases (UniProt: P13798). It is primarily responsible for the hydrolysis of N-terminally acetylated peptides, releasing N-acetylated amino acids, which is a crucial step in the degradation of proteins that have undergone N-terminal acetylation (PubMed: 25108285). Beyond its role in general protein turnover, APEH also functions as an oxidized protein hydrolase (OPH), playing a vital role in the clearance of proteins damaged by oxidative stress to maintain cellular proteostasis (PubMed: 11553618). The APEH gene is located on chromosome 3p21.3, a region frequently deleted in various cancers, particularly small cell lung cancer, suggesting its potential role as a tumor suppressor (PubMed: 8221615). APEH is highly sensitive to inhibition by organophosphorus (OP) compounds, and its activity in erythrocytes is often used as a sensitive biomarker for OP exposure in humans (PubMed: 16126140). Recent evidence also indicates that APEH inhibition can synergize with proteasome inhibitors to induce apoptosis in cancer cells, making it a potential target for combination therapies in oncology (PubMed: 23671653). In neurodegenerative contexts, APEH has been studied for its potential role in the metabolism of peptides associated with Alzheimer's disease (PubMed: 22403114). Overall, APEH serves as a key enzyme in both protein catabolism and cellular defense against oxidative damage.

Other names

N-acylaminoacyl-peptide hydrolaseAcylamino-acid-releasing enzyme (AARE)Oxidized protein hydrolase (OPH)Acylaminoacyl-peptidase

APEH is inhibited through the covalent modification of its active-site serine residue (Ser587), which is part of a catalytic triad (Ser-Asp-His). This inhibition prevents the enzyme from cleaving N-acetylated amino acids from the N-terminus of peptides, leading to the accumulation of acetylated and oxidized proteins (UniProt: P13798; PubMed: 16126140).