title: Amino acid absorption and homeostasis in mice lacking the intestinal peptide transporter PEPT1.
abstract: The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Neither gene expression nor proteome profiling nor functional analysis revealed evidence for any compensatory changes in the levels and/or function of transporters for free amino acids in the intestine. However, most plasma amino acid levels were increased in Pept1(-/-) compared with Pept1(+/+) animals, suggesting that amino acid handling is altered. Plasma appearance rates of (15)N-labeled amino acids determined after intragastric administration of a low dose of protein remained unchanged, whereas administration of a large protein load via gavage revealed marked differences in plasma appearance of selected amino acids. PEPT1 seems, therefore, important for overall amino acid absorption only after high dietary protein intake when amino acid transport processes are saturated and PEPT1 can provide additional absorption capacity. Since renal amino acid excretion remained unchanged, elevated basal concentrations of plasma amino acids in PEPT1-deficient animals seem to arise mainly from alterations in hepatic amino acid metabolism.
authors.affiliation: ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany.
authors.forename: Anna-Maria
authors.initials: AM
authors.lastname: Nässl
authors.forename: Isabel
authors.initials: I
authors.lastname: Rubio-Aliaga
authors.forename: Henning
authors.initials: H
authors.lastname: Fenselau
authors.forename: Mena Katharina
authors.initials: MK
authors.lastname: Marth
authors.forename: Gabor
authors.initials: G
authors.lastname: Kottra
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
mesh_terms: D000596:Amino Acids / Q000097:blood / Q000378:metabolism*; D000818:Animals; D004044:Dietary Proteins / Q000008:administration & dosage*; D020869:Gene Expression Profiling; D006706:Homeostasis; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008871:Microvilli / Q000378:metabolism; D000074011:Peptide Transporter 1; D020543:Proteome / Q000378:metabolism; D027981:Symporters / Q000235:genetics / Q000378:metabolism*
chemical_list: D000596:Amino Acids; D004044:Dietary Proteins; D000074011:Peptide Transporter 1; D020543:Proteome; C489941:Slc15a1 protein, mouse; D027981:Symporters