Transport of the advanced glycation end products alanylpyrraline and pyrralylalanine by the human proton-coupled peptide transporter hPEPT1.
The glycation compound pyrraline, which originates from the advanced Maillard reaction, appears in urine after consumption of pyrraline-containing food. We hypothesized that the absorption of pyrraline occurs in the form of dipeptides rather than the free amino acid. The human intestinal peptide transporter hPEPT1 was transiently expressed in HeLa cells. In hPEPT1-transfected cells but not in cells transfected with empty vector, the uptake of [(14)C]glycylsarcosine was strongly inhibited by alanylpyrraline (Ala-Pyrr) and pyrralylalanine (Pyrr-Ala). Free pyrraline did not inhibit peptide uptake. In Xenopus laevis oocytes expressing human PEPT1, both Ala-Pyrr and Pyrr-Ala generated significant inward directed currents. In a third approach, uptake of the dipeptides into hPEPT1-transfected HeLa cells was analyzed by HPLC. Ala-Pyrr and Pyrr-Ala were taken up by hPEPT1-expressing cells at a 4- to 7-fold higher rate than by HeLa cells transfected with the empty vector. We conclude that pyrraline containing dipeptides are transported by hPEPT1 in an electrogenic manner into intestinal cells.
Geissler
Stefanie
S
Membrane Transport Group, Biozentrum, Martin-Luther-University Halle-Wittenberg, D-06120 Halle, Germany.
Hellwig
Michael
M
Zwarg
Madlen
M
Markwardt
Fritz
F
Henle
Thomas
T
Brandsch
Matthias
M
D000409:Alanine / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000235:genetics / Q000502:physiology; D018076:DNA, Complementary / Q000235:genetics; D004151:Dipeptides / Q000378:metabolism; D005822:Genetic Vectors; D017127:Glycation End Products, Advanced / Q000378:metabolism*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D015416:Maillard Reaction; D009646:Norleucine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000652:urine; D009865:Oocytes / Q000378:metabolism; D000074011:Peptide Transporter 1; D011758:Pyrroles / Q000378:metabolism* / Q000652:urine; D015183:Restriction Mapping; D027981:Symporters / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014982:Xenopus laevis / Q000378:metabolism
D018076:DNA, Complementary; D004151:Dipeptides; D017127:Glycation End Products, Advanced; D000074011:Peptide Transporter 1; D011758:Pyrroles; C082186:SLC15A1 protein, human; D027981:Symporters; C059571:2-formyl-5-(hydroxymethyl)pyrrole-1-norleucine; D009646:Norleucine; D000409:Alanine