FIG 8.

Steady-state metabolite concentrations reveal effects of MPC deficiency and compensatory metabolic adaptations. (A) Distribution of total metabolites identified by unbiased metabolomics across molecular classes compared to the distribution of significantly regulated metabolites in e17.5 brain and liver. (B) Metabolites detected in both brain and liver that were significantly regulated by Mpc1 deficiency. The values shown are fold changes relative to the WT, and red and green indicate significant up- and downregulation, respectively (P < 0.05 by Welch's two-sample t test; n = 8). Shown are select metabolites directly related to pyruvate metabolism, TCA cycle intermediates, select amino acids, and select lipid metabolites. An additional list of significantly regulated metabolites is provided in Table S1 in the supplemental material. IMM, inner mitochondrial membrane; OMM, outer mitochondrial membrane; cit, citrulline; ASA, argininosuccinic acid. (C) Steady-state concentrations of alanine (ala), glutamate (glu), and aspartate (asp) in Mpc1^D/D primary MEFs relative to WT MEFs. (D) [2-¹³C]pyruvate flux. m + 1-labeled metabolites over total metabolite abundance, determined by LC-MS, are shown relative to the WT (means plus SEM; n = 4). *, 0.01<P < 0.05; **, P < 0.01; pairwise comparison to the WT after one-way ANOVA. α-kg, α-ketoglutarate.