Extended Data Fig. 5: The role of transamidase-dependent glutamine catabolism.
From: Identifying strategies to target the metabolic flexibility of tumours
a, A correlation between the gene expression level of Gls1 and different amidotransferases analyzed from the TCGA human Hepatocellular Carcinoma Provisional mRNA dataset (https://www.cancer.gov/tcga, RNA Seq V2, 371 patients / 373 samples). Modified from cBioPortal68,69. b, A representative full 1H-15N 2D-HMBC NMR spectra of the polar fraction of a CT tumour from a mouse infused for three hours with amido-15N-glutamine. Shows the regions of interest (R.O.I) of the signals from the indicated metabolites as the results of the 15N-incorporation from the amide group of glutamine during in vivo infusions. c, top panel: quantification of the [amido-15N]glutamine-derived enrichment of different metabolites, including nucleosides, in tumours from mice infused with amido-15N-glutamine (n = 3 mice per group); LC-MS; and bottom panel: cells isolated from the tumours and incubated with 2 mM amido-[15N]glutamine for 48 h (n = 3 independent experiments); LC-MS. Data are presented as mean ± S.D. Statistical analysis was performed using a two-tailed Student’s t-test. Complete list of exact P values is provided as a source data file. d, 1H-15N 2D-HMBC NMR spectra of the serum of mice infused with amido-[15N]glutamine, demonstrating the presence of labelled amino acids. e, Representative region of the 1H-15N 2D-HMBC NMR spectra of CT MYC liver tumours from mice treated with the vehicle or 25 mg/kg of the pan-amidotransferase inhibitor DON, infused with amido-[15N]glutamine. Note the DON-dependent suppression of the 15N incorporation.
