Peptide transporter 1 (SLC15A1) (PEPT1)

Peptide transporter 1 (PEPT1), encoded by the SLC15A1 gene, is a proton-coupled oligopeptide transporter primarily expressed in the apical membrane of small intestinal enterocytes and renal proximal tubule cells.[1][3][11] It mediates the electrogenic uphill transport of di- and tripeptides derived from dietary protein digestion, utilizing a proton gradient and inside-negative membrane potential as driving forces, without sodium dependence.[2][3][6] This high-capacity, low-affinity transporter (Km 0.2-10 mM) ensures efficient nitrogen supply by absorbing peptides in a sequence-independent manner, complementing intracellular hydrolysis by peptidases.[1][3] PEPT1 also facilitates oral bioavailability of peptidomimetic drugs, including beta-lactam antibiotics, ACE inhibitor prodrugs like captopril, and antivirals such as valacyclovir, through prodrug strategies that exploit its broad substrate specificity.[3][7][12] Structurally, it belongs to the POT/SLC15 family, operating via a rocker-switch mechanism with distinct outward- and inward-facing conformations, as revealed by recent cryo-EM structures.[4][6][8] In disease, PEPT1 is upregulated in inflammatory bowel disease colons, potentially transporting bacterial peptides to trigger inflammation, though clinical polymorphisms have limited known impacts.[3][10] While not a direct therapeutic target, its role in drug absorption makes it valuable for enhancing oral delivery of poorly absorbed compounds.[3][7]

Other names

solute carrier family 15 member 1SLC15A1HPEPT1HPECT1

Proton-coupled cotransport of di- and tripeptides and peptidomimetic prodrugs, High-capacity low-affinity uptake via rocker-switch mechanism