Fig. 5.

Metabolomics profile of postnatal Gpt2-null mouse brain. (A) Overrepresentation analysis of metabolomics in brains from Gpt2-null (MUT) compared with WT Gpt2 mice at P18. The reference library contained 88 metabolite sets for normal metabolic pathways. Metabolites showing significant increases or decreases (compared with control on Student’s t test P value less than 0.05) were flagged. The hypergeometric test was used to determine whether flagged metabolites from specific pathways were significantly overrepresented. Red, FDR < 0.01; green, 0.01 < FDR < 0.03; blue, 0.03 < FDR < 0.05. (B–E) Box plots of metabolites, with whiskers representing minimum and maximum values. The peak intensity areas were normalized by a pooled reference sample from the WT Gpt2 group (probabilistic quotient normalization), and auto (unit) scaling was performed whereby the data were mean-centered and divided by the SD of each group. Unpaired Student’s t test was performed assuming equal group variance. The box plots in each of the panels show the following: (B) metabolites from the primary GPT enzyme reaction, (C) amino acids, (D) TCA cycle intermediates, and (E) metabolites involved in neuroprotective mechanisms. n = 6 WT animals and 6 MUT animals. * = 0.01 < raw P < 0.05, ** = 0.001 < P < 0.01, *** = P < 0.001. Red stars denote a corresponding FDR below 0.05. Also refer to SI Appendix, Table S5, for MSEA data; SI Appendix, Table S6, for full set of metabolite Student’s t tests; and SI Appendix, Table S7, for raw data. ^†Arginine is a conditionally essential amino acid.