The nutritional source for catabolism in the tricarboxylic acid (TCA) cycle is a fundamental question in metabolic physiology. Limited by data and mathematical analysis, controversy exists. Using isotope-labeling data in vivo across several experimental conditions, we construct multiple models of central carbon metabolism and develop methods based on metabolic flux analysis (MFA) to solve for the preferences of glucose, lactate, and other nutrients used in the TCA cycle. We show that in nearly all circumstances, glucose contributes more than lactate as a substrate to the TCA cycle. This conclusion is verified in different animal strains from different studies and different administrations of ¹³C glucose, and is extended to multiple tissue types. Thus, this quantitative analysis of organismal metabolism defines the relative contributions of nutrient fluxes in physiology, provides a resource for analysis of in vivo isotope tracing data, and concludes that glucose is the major nutrient used in mammals.

三羧酸 (TCA) 循环中分解代谢的营养来源是代谢生理学中的一个基本问题。受数据和数学分析的限制，存在争议。我们在多个实验条件下使用体内同位素标记数据，构建了多个中心碳代谢模型，并开发了基于代谢通量分析 (MFA) 的方法，以解决 TCA 循环中使用的葡萄糖、乳酸和其他营养素的偏好。我们表明，在几乎所有情况下，葡萄糖作为 TCA 循环的底物都比乳酸贡献更多。这一结论在来自不同研究和不同给药的不同动物品系中得到了验证¹³C 葡萄糖，并扩展到多种组织类型。因此，这种有机体代谢的定量分析定义了营养通量在生理学中的相对贡献，为分析体内同位素示踪数据提供了资源，并得出结论，葡萄糖是哺乳动物中使用的主要营养物质。