MPC deficiency alters the flux of glycolytic pyruvate into the TCA cycle and is compensated by increased glutamine-driven anaplerosis and reductive TCA cycle.
(A) The steady-state abundance relative to MPC1+/+ (dotted line) of the indicated metabolites in MPC1gt/gt (light grey bars) and MPC1-Flag rescued MEFs (dark grey bars) was determined by targeted metabolomics. (B,C) Mass isotopomer distribution (MID) of succinate, malate and aspartate in MPC1+/+ (black bars) and MPC1gt/gt (grey bars) MEFs cultured in the presence of (B) [U-13C]glucose or (C) [U-13C]glutamine. (D) m+1 fraction of aspartate, malate and succinate in MPC1+/+ (black bars) and MPC1gt/gt (grey bars) MEFs cultured in the presence of [1-13C]glutamine. xPG: 2-/3-phosphoglycerate; PEP: phosphoenolpyruvate; Pyr: pyruvate; Lac: lactate; Asp: aspartate; Fum: fumarate; Mal: malate; Cit-IsoCit: citrate-isocitrate.