Molecular physiological studies on the peptide transporter-1, PepT1.

The peptide transporter-1, PepT1, is responsible for the uptake of peptides in the mammalian intestine after protein digestion. It has also been shown to transport a wide range of pharmacological agents; thus making it important in drug design and delivery. Many studies have addressed structure-function relationships in the transporter, using biochemical and uptake assays; however PepT1 is an electrogenic transporter whose activities could be more clearly studied using electrophysiological methods. In this work therefore, the transporter has been studied using the two electrode voltage clamp technique on the transporter expressed in Xenopus laevis oocytes. Temperature effects on the kinetics of the three isoforms studied (rabbit, zebrafish, seabass) is reported here with a suggestion of a possible structural adaptation in the transporter. Since the transporter is also of interest in animal feed formulation, transport characteristics of a range of dipeptide combinations are also presented; with a recommendation on the possible optimal lysine supplementation in feeds that require essential amino acids supplementation. Reverse operation in transporters may be the result of or lead to pathophysiological states. Experimental data here show that mutants in Arginine 282 and aspartate 341 exhibit properties that make them suitable as models to study possible reverse operation in PepT1. To understand the physiological significance of reverse operation, the structural and functional basis of this phenomenon was also explored.