Analysis of the interaction between tryptophan-related compounds and ATP-binding cassette transporter G2 (ABCG2) using targeted metabolomics

ATP-binding cassette transporter G2 (ABCG2) is involved in the secretion of several compounds in milk. The in vitro and in vivo interactions between tryptophan-related compounds and ABCG2 were investigated. The tryptophan metabolome was determined by liquid chromatography-tandem mass spectrometry in...

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Detalles Bibliográficos
Autores: García-Lino, Alba M., Gómez-Gómez, Àlex, García-Mateos, Dafne, de la Fuente, Alvaro, Álvarez, Ana, Pozo Mendoza, Óscar J., 1975-, Merino, Gracia
Tipo de recurso: artículo
Estado:Versión aceptada para publicación
Fecha de publicación:2021
País:España
Institución:Universitat Pompeu Fabra
Repositorio:Repositorio Digital de la UPF
OAI Identifier:oai:repositori.upf.edu:10230/48011
Acceso en línea:http://hdl.handle.net/10230/48011
http://dx.doi.org/10.1016/j.foodchem.2020.128665
Access Level:acceso abierto
Palabra clave:ATP binding cassette transporter G2
In vivo
Metabolome
Mice
Tryptophan
Descripción
Sumario:ATP-binding cassette transporter G2 (ABCG2) is involved in the secretion of several compounds in milk. The in vitro and in vivo interactions between tryptophan-related compounds and ABCG2 were investigated. The tryptophan metabolome was determined by liquid chromatography-tandem mass spectrometry in milk and plasma from wild-type and Abcg2-/- mice as well as dairy cows carrying the ABCG2 Y581S polymorphism (Y/S) and noncarrier animals (Y/Y). The milk-to-plasma ratios of tryptophan, kynurenic acid, kynurenine, anthranilic acid, and xanthurenic acid were higher in wild-type mice than in Abcg2-/- mice. The ratio was 2-fold higher in Y/S than in Y/Y cows for kynurenine. In vitro transport assays confirmed that some of these compounds were in vitro substrates of the transporter and validated the differences observed between the two variants of the bovine protein. These findings show that the secretion of metabolites belonging to the kynurenine pathway into milk is mediated by ABCG2.