Interaction between the pentose phosphate pathway and gluconeogenesis from glycerol in the liver

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30 Scopus citations


After exposure to [U-13C3]glycerol, the liver produces primarily [1,2,3-13C3]- and [4,5,6-13C3]glucose in equal proportions through gluconeogenesis from the level of trioses. Other 13C-labeling patterns occur as a consequence of alternative pathways for glucose production. The pentose phosphate pathway (PPP), metabolism in the citric acid cycle, incomplete equilibration by triose phosphate isomerase, or the transaldolase reaction all interact to produce complex 13C-labeling patterns in exported glucose. Here, we investigated 13C labeling in plasma glucose in rats given [U-13C3]glycerol under various nutritional conditions. Blood was drawn at multiple time points to extract glucose for NMR analysis. Because the transaldolase reaction and incomplete equilibrium by triose phosphate isomerase cannot break a 13C-13C bond within the trioses contributing to glucose, the appearance of [1,2-13C2]-, [2,3-13C2]-, [5,6-13C2]-, and [4,5-13C2]glucose provides direct evidence for metabolism of glycerol in the citric acid cycle or the PPP but not an influence of either triose phosphate isomerase or the transaldolase reaction. In all animals, [1,2-13C2]glucose/[2,3-13C2]glucose was significantly greater than [5,6-13C2]glucose/[4,5-13C2]glucose, a relationship that can only arise from gluconeogenesis followed by passage of substrates through the PPP. In summary, the hepatic PPP in vivo can be detected by 13C distribution in blood glucose after [U-13C3]glycerol administration.

Original languageEnglish (US)
Pages (from-to)32593-32603
Number of pages11
JournalJournal of Biological Chemistry
Issue number47
StatePublished - Nov 21 2014

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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