PEPTs

PEPTs, or peptide transporters, are a family of membrane transport proteins that mediate the cellular uptake of di- and tri-peptides across biological membranes. In humans, PEPTs refer mainly to the SLC15 family, particularly PEPT1 (SLC15A1) and PEPT2 (SLC15A2).

PEPT1 is highly expressed in the small intestine and facilitates dietary peptide absorption; PEPT2 is mainly expressed in the kidney and also in other tissues, enabling reabsorption and distribution of peptides. They are proton-coupled oligopeptide transporters, belonging to the POT family, that drive peptide uptake via a symport mechanism with protons.

Substrates include di- and tri-peptides generated from dietary proteins, as well as various peptide-like drugs and prodrugs, such as cephalexin, valacyclovir, and certain ACE inhibitors. The transporters have broad substrate specificity and can be inhibited or outcompeted by other dipeptides.

Structurally, PEPT1 and PEPT2 are multipass membrane proteins, typically with about 12 transmembrane segments, and operate using the electrochemical H+ gradient across the cell membrane. Regulation occurs at transcriptional and post-translational levels in response to dietary and physiological cues.

Clinical and pharmacological significance includes their impact on oral drug bioavailability and renal clearance, variability due to genetics or co-administered substrates, and potential as targets in drug design and disease research.