dehydropeptidase

Dehydropeptidase refers to a small family of zinc-dependent metallopeptidases that hydrolyze dehydropeptides. In humans, the best characterized members are dehydropeptidase I (DHP-I) and dehydropeptidase II (DHP-II). DHP-I is a membrane-bound dipeptidase located primarily in the proximal renal tubule brush border, while DHP-II is a soluble cytosolic enzyme with broader tissue distribution, including kidney and liver. Both enzymes participate in the metabolism of short peptides by cleaving N-terminal dipeptides from substrates that resemble dehydropeptides, and they can act on peptide-like drugs that contain dehydropeptide structures.

Pharmacologically, DHP-I is notable for inactivating certain beta-lactam antibiotics, such as imipenem, by hydrolyzing the antibiotic and reducing its renal persistence. Cilastatin, a DHP-I inhibitor, is co-administered with imipenem to prevent this degradation and to preserve antibacterial activity in the urine. DHP-II inhibitors are less widely used clinically, but the enzyme can influence peptide metabolism and the disposition of some drugs and prodrugs.

Physiological and clinical relevance centers on peptide handling and drug interactions. Variations in dehydropeptidase activity can affect how short peptides and certain therapeutics are metabolized and cleared, though clinically significant deficiencies are rare. Research into dehydropeptidases addresses substrate specificity, tissue distribution, and potential implications for pharmacokinetics and peptide signaling pathways.