Solute carrier family 15 member 1 (PEPT1) (PEPT1)

Solute carrier family 15 member 1 (PEPT1) is a high-capacity, low-affinity proton-coupled transporter primarily located on the apical membrane of enterocytes in the small intestine (UniProt: P46059). Its primary physiological role is the absorption of di- and tripeptides resulting from the digestion of dietary proteins, which is essential for maintaining nitrogen balance (PubMed: 15102879). PEPT1 is highly significant in pharmacology because it recognizes and transports a wide variety of peptidomimetic drugs, including beta-lactam antibiotics, ACE inhibitors, and various prodrugs (DrugBank: DB00515). By conjugating poorly absorbed drugs to amino acids or peptides, researchers utilize PEPT1 to significantly enhance oral bioavailability, as seen with the antiviral prodrug valacyclovir (PubMed: 23133515). While normally absent or lowly expressed in the colon, PEPT1 expression is upregulated during chronic inflammation, such as in Crohn's disease, where it may transport bacterial peptides that trigger immune responses (PubMed: 11564675). Consequently, PEPT1 serves as both a critical pathway for drug delivery and a potential factor in the pathogenesis of intestinal inflammatory disorders (PubMed: 25653464).

Other names

SLC15A1Peptide transporter 1H+/peptide cotransporter 1Oligopeptide transporter 1

PEPT1 facilitates the transmembrane transport of di- and tripeptides and peptidomimetic drugs via a proton-coupled mechanism, utilizing an inwardly directed proton gradient and negative membrane potential to drive substrate uptake into cells (PubMed: 23133515).