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

Abstract

Milk is the main source of the essential amino acid tryptophan and its metabolites for sucklings. The main pathway in tryptophan metabolism is the kynurenine pathway that generates several bioactive metabolites with relevant health effects, including prevention of neurodegenerative disorders. ABCG2 transporter participates in milk secretion of different compounds. Our aim was to provide a comprehensive overview of the in vitro and in vivo interactions between tryptophan-related compounds and ABCG2. Tryptophan metabolome was analysed in milk and plasma from wild-type and Abcg2-/- 40 mice using liquid chromatography-tandem mass spectrometry. Our results show that Abcg2 mediates the secretion of kynurenic acid, kynurenine, anthranilic acid and xanthurenic acid into milk. Complementary metabolome analysis revealed that the bovine ABCG2 Y581S polymorphism increases kynurenine concentration in cow milk. All these results show the relevance of the interaction of ABCG2 and tryptophan-related compounds present in milk and its potential effect on health, mainly in postnatal development.