Glucose feeds the TCA cycle via circulating lactate

https://www.nature.com/articles/nature24057

Sheng Hui, Jonathan M. Ghergurovich, Raphael J. Morscher, Cholsoon Jang, Xin Teng, Wenyun Lu, Lourdes A. Esparza, Tannishtha Reya, Le Zhan, Jessie Yanxiang Guo, Eileen White & Joshua D. Rabinowitz

• When oxygen is present, it is commonly thought that glucose (derived from the food we eat) is catabolised via glycolysis to pyruvate, which is then transported into mitochondria, fuelling the TCA cycle and oxidative phosphorylation. Alternatively, when oxygen is less available, glucose can be catabolised to lactate.
• Although traditionally thought of as a waste product, it is becoming increasingly clear that lactate can itself be used as a fuel molecule
• Here, the authors investigate the relative contribution of glucose and lactate to feeding the TCA cycle in mice, across various tissues
• In fasting mice, the contribution of glucose to the TCA cycle is primarily via circulating lactate in all tissues except the brain
• The circulatory turnover of lactate is the highest of all metabolites, exceeding that of glucose in both the fed and fasted state
• In tumours, lactate is a primary TCA substrate