Comparison of the transport characteristics of D- and L-methionine in a human intestinal epithelial model (Caco-2) and in a perfused rat intestinal model.
Absorption mechanisms of L- and D-methionine (MET) in an in vitro cultured human intestinal epithelial cell model (Caco-2) and an in situ perfused rat intestinal model were investigated to determine if the kinetic characteristics of absorption are comparable in these two popular absorption models. The results indicate that the transport of L- and D-MET were concentration-dependent in both model systems, and displayed comparable Km values. The Km value for L-MET is 1.34 mM in the Caco-2 model and 3.6 mM in the perfused rat intestinal model, while the Km value for D-MET is 1.79 mM in the Caco-2 model and 2.87 mM in the perfused rat intestinal model. Although the Jmax values were not comparable because of significant methodology differences, the Jmax values for L-MET were always higher than that for D-MET. In addition, transport of L- and D-MET across the Caco-2 cell monolayers were also inhibited by 10 mM Phe and Lys while MeAIB, Pro and Glu were generally ineffective. Similar results were also observed with these inhibitors in the perfused rat intestinal model with the exception that a combination of Pro and Glu stimulated the uptake of L-MET. In conclusion, the transport characteristics of L- and D-MET are comparable in both model systems.
Zheng
L
L
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman 99164-6510.
Chen
J
J
Zhu
Y
Y
Yang
H
H
Elmquist
W
W
Hu
M
M
D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D007413:Intestinal Mucosa / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
D008715:Methionine