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. 2017 Aug 16;7:8489. doi: 10.1038/s41598-017-08277-3

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© The Author(s) 2017

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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The metabolic pathways that generate various lactate isotopomers and isotopologues in 4T1 cells, traced by [U-¹³C] glucose. Besides [U-¹³C]lactate, there are trace amount of other lactate isotopologues, which could be generated from [U-¹³C]pyruvate through tricarboxylic cycle to produce [1,2-¹³C₂]malate and [3,4-¹³C₂]malate, which, via catalysis of malic enzyme, generate [1,2-¹³C₂]pyruvate and [3-¹³C]pyruvate, which can convert to corresponding lactate. [1,2-¹³C₂]pyruvate and [3-¹³C]pyruvate can enter Krebs cycle, leading to generation of other lactate isotopomers.