PepT

PEPT refers to a group of peptide transporters that mediate the proton-coupled uptake of di- and tri-peptides, as well as a broad range of peptide-like drugs. In mammals, the best characterized members are PEPT1 and PEPT2, encoded by SLC15A1 and SLC15A2. These transporters belong to the solute carrier family SLC15 and are part of the proton-dependent oligopeptide transporter (POT) family.

PEPT1 is primarily expressed in the brush-border membrane of intestinal enterocytes, where it contributes to the dietary absorption of small peptides and many peptide-like drugs. PEPT2 is mainly found in the proximal tubules of the kidney and serves a key role in reabsorbing filtered peptides and contributing to drug disposition. Both transporters have overlapping substrate specificity and can transport a wide variety of dipeptides and some tripeptides, as well as peptidomimetic drug compounds.

Mechanistically, PEPT transport is driven by the inward proton gradient, functioning as H+-coupled symporters. The transport process uses the proton motive force to move substrates against their concentration gradient, often with broad substrate tolerance and high capacity. Structurally, these proteins typically span the membrane multiple times (commonly around 12 transmembrane helices) and operate via an alternating-access mechanism.

Substrates include dietary peptides, certain antibiotics (notably penicillins and cephalosporins), ACE inhibitors, and other peptide-like drugs. The activity and expression of PEPT1 and PEPT2 influence oral drug bioavailability, renal clearance, and overall pharmacokinetics. Variants or inhibitors of these transporters can affect drug absorption and interactions, making PEPTs a relevant consideration in pharmaceutical design and personalized medicine.