Renal dehydropeptidase I (Dipeptidase 1) (DHP-I)

Renal dehydropeptidase I (DHP-I), also known as Dipeptidase 1 (DPEP1), is a zinc-dependent metalloenzyme primarily located on the brush border membrane of the renal proximal tubules (UniProt: P16444). Its physiological role involves the hydrolysis of various dipeptides and the conversion of leukotriene D4 into leukotriene E4. In clinical pharmacology, DHP-I is a significant therapeutic target because it rapidly degrades carbapenem antibiotics, such as imipenem, into inactive and potentially nephrotoxic metabolites (PubMed: 32899204). To ensure the efficacy and safety of these antibiotics, DHP-I inhibitors like cilastatin are co-administered, which prevents renal degradation and extends the half-life of the drug (NIH: PubChem). Although the user referred to it as "Bacterial dehydropeptidase I," the enzyme is actually a human host protein; bacterial resistance to carbapenems is typically mediated by distinct enzymes known as carbapenemases, though some bacterial metallo-beta-lactamases (e.g., CphA) share structural similarities and can also be inhibited by cilastatin (Antimicrob Agents Chemother. 1995; 39: 1629-1631).

Other names

Dehydropeptidase IDHP-IDipeptidase 1DPEP1Renal dipeptidaseMicrosomal dipeptidaseMembrane dipeptidase

Inhibition of renal dehydropeptidase I prevents the hydrolysis of carbapenem antibiotics in the kidneys, thereby maintaining therapeutic systemic levels and preventing the formation of nephrotoxic metabolites.