FIGURE 4.

Strategy utilized for the en masse identification of endogenous OAT substrates. An untargeted metabolomics analysis strategy used to identify endogenous substrates of the Oats is depicted (279, 285). Samples of body fluids [e.g., blood/plasma (B/P; red) and urine (U; yellow)] were collected from wild-type (WT) and Oat-deficient (KO) mice, and extracts of these specimens were subjected to reverse-phase liquid chromatography (LC) followed by time-of-flight mass spectrophotometry (MS TOF) (279). LC-MS features were statistically ranked and aligned based on their mass, time of flight, and intensity (224). Metabolites with significant differences between WT and Oat-KO mice were identified by searching available metabolomics databases. The ability of some of the identified metabolites to interact with Oats was then validated in wet-lab functional assays (279, 285). [From Wikoff et al. (279). Copyright 2011 American Chemical Society.]