PepT1

PepT1, or peptide transporter 1, is a proton-dependent oligopeptide transporter encoded by the SLC15A1 gene. It is a member of the SLC15 family and plays a central role in the intestinal absorption of di- and tri-peptides derived from dietary proteins, as well as in the renal reabsorption of filtered peptides. Its broad substrate specificity also permits transport of peptide-like drugs and certain prodrugs, influencing oral bioavailability and pharmacokinetics.

Localization and mechanism are key features of PepT1. In the small intestine, it is located on the apical (brush border) membrane of enterocytes, where it functions as a proton-coupled symporter. By utilizing the inward proton gradient, PepT1 transports peptides into the cell without relying on sodium gradients. It is generally considered a high-capacity, low-affinity transporter, efficient at taking up a wide range of peptides at physiological luminal pH levels.

Substrates and regulation are diverse. PepT1 accommodates many di- and tri-peptides with variable N- and C-terminal residues, and it also transports peptide-like molecules such as certain beta-lactam antibiotics and peptide-based prodrugs. Its activity increases in more acidic conditions and can be modulated by dietary protein intake, hormonal signals, and disease states that affect intestinal physiology. In the kidney, PepT1 contributes to reabsorption of small peptides from the glomerular filtrate, complementing PepT2, which has a different tissue distribution and affinity profile.

Genetic and clinical considerations include its role in drug absorption and potential interactions with competing substrates. PepT1 is distinct from PepT2, which has higher affinity and is more prominent in renal and other tissues.