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. 2019 Nov 11;9:16480. doi: 10.1038/s41598-019-52952-6

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© The Author(s) 2019

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Metabolic parameters obtained by ¹³C NMR isotopomer analysis of tissue glutamate. (A) glutamate C-4 (34.20 ppm) and C-3 (27.60 ppm) resonances; (B) a metabolic scheme showing ¹³C-labeling of glutamate isotopomers; (C) oxygen consumption; (D) contribution of glycogen to the total lactate pool; (E) fractional oxidation of ¹³C-lactate/¹³C-pyruvate and endogenous sources for energy production by the TCA cycle; (F) pyruvate dehydrogenase (PDH) flux; and (G) tricarboxylic acid cycle (TCA) flux. The letters S, D, T, and Q refer to a singlet, doublet (with the relevant J-coupled spins), triplet (a degenerate doublet of doublets), and quartet (or doublet of doublets), respectively. Filled circles in the metabolic scheme represent ¹³C-enriched carbons while open circles represent natural abundance levels of ¹³C. ¹³C-enriched pyruvate and lactate supplied in the perfusion medium are shown in red in (B). For viewing simplicity, only ¹³C-labeled glutamate isotopomers generated after the 1^st and 2^nd turns are shown. ¹³C-labeling patterns of other metabolites can be generated using tcaSIM and tcaCALC (downloadable free of charge at http://www.invivometabolism.org/tca.html. Abbreviations: α-KG = α-ketoglutarate; ALT = alanine transaminase; CYTO = cytosol; G3P = glyceraldehyde 3-phosphate; GLU = glutamate; LDH = lactate dehydrogenase; MITO = mitochondria; MPC1/2 = mitochondrial pyruvate carrier 1 and 2; PDH = pyruvate dehydrogenase complex; PDK = pyruvate dehydrogenase kinase; PC = pyruvate carboxylase; PEP = phosphoenolpyruvate; PEPCK = phosphoenolpyruvate carboxykinase, TCA = tricarboxylic acid; and gww = gram wet weight. The bar plots represent the mean ± SD (n = 4 per group) with significance indicated by “*” (P < 0.05) and “**” (P < 0.001).