Dipeptidase 1 (DPEP1) (DPEP1)

Dipeptidase 1 (DPEP1), frequently referred to as renal dehydropeptidase-I, is a glycosyl-phosphatidylinositol (GPI)-anchored zinc-dependent metalloenzyme primarily localized to the brush border membrane of the renal proximal tubules (UniProt P16444). It plays a critical role in the metabolism of various dipeptides and is specifically responsible for the conversion of leukotriene D4 into leukotriene E4, as well as the hydrolysis of glutathione and its conjugates (PubMed: 2455111). In a clinical context, DPEP1 is the primary enzyme responsible for the degradation of carbapenem antibiotics, such as imipenem, into inactive and potentially nephrotoxic metabolites (PubChem CID 5280459). Consequently, the DPEP1 inhibitor cilastatin is standardly co-administered with imipenem to prevent this degradation, thereby enhancing the antibiotic's efficacy and reducing renal toxicity (PubMed: 3015456). Recent research also highlights DPEP1 as a potential therapeutic target in acute kidney injury and a biomarker in various malignancies, including colorectal and pancreatic cancers (PubMed: 31434690). The enzyme's involvement in neutrophil recruitment during inflammation further expands its potential as a target for treating systemic inflammatory response syndrome (PubMed: 31434690).

Other names

Dehydropeptidase IRenal dipeptidaseMicrosomal dipeptidaseMDPRDPDHP-I

Competitive inhibition of the enzyme to prevent the hydrolysis of carbapenem antibiotics and reduce renal toxicity.