Quantitative Analysis of the Physiological Contributions of Glucose to the TCA Cycle.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Liu, S; Dai, Z; Cooper, DE; Kirsch, DG; Locasale, JW

Published Date

  • October 6, 2020

Published In

Volume / Issue

  • 32 / 4

Start / End Page

  • 619 - 628.e21

PubMed ID

  • 32961109

Pubmed Central ID

  • PMC7544667

Electronic International Standard Serial Number (EISSN)

  • 1932-7420

Digital Object Identifier (DOI)

  • 10.1016/j.cmet.2020.09.005


  • eng

Conference Location

  • United States