title: Interaction between the pentose phosphate pathway and gluconeogenesis from glycerol in the liver.
abstract: After exposure to [U-(13)C3]glycerol, the liver produces primarily [1,2,3-(13)C3]- and [4,5,6-(13)C3]glucose in equal proportions through gluconeogenesis from the level of trioses. Other (13)C-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 (13)C-labeling patterns in exported glucose. Here, we investigated (13)C labeling in plasma glucose in rats given [U-(13)C3]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 (13)C-(13)C bond within the trioses contributing to glucose, the appearance of [1,2-(13)C2]-, [2,3-(13)C2]-, [5,6-(13)C2]-, and [4,5-(13)C2]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-(13)C2]glucose/[2,3-(13)C2]glucose was significantly greater than [5,6-(13)C2]glucose/[4,5-(13)C2]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 (13)C distribution in blood glucose after [U-(13)C3]glycerol administration.
authors.affiliation: From the Advanced Imaging Research Center and Departments of Internal Medicine and eunsook.jin@utsouthwestern.edu.
authors.forename: Eunsook S
authors.initials: ES
authors.lastname: Jin
authors.affiliation: From the Advanced Imaging Research Center and Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, the Department of Chemistry, University of Texas at Dallas, Richardson, Texas 75080, and.
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.affiliation: From the Advanced Imaging Research Center and Departments of Internal Medicine and Radiology, University of Texas Southwestern Medical Center, Dallas, Texas 75390, the Veterans Affairs North Texas Health Care System, Dallas, Texas 75216.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002247:Carbon Isotopes; D005943:Gluconeogenesis; D005990:Glycerol / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D010427:Pentose Phosphate Pathway; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014153:Transaldolase / Q000378:metabolism; D014305:Triose-Phosphate Isomerase / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002247:Carbon Isotopes; D007773:Lactates; D014153:Transaldolase; D014305:Triose-Phosphate Isomerase; D005990:Glycerol
keywords: Gluconeogenesis; Glucose Metabolism; Glycerol; Liver Metabolism; Nuclear Magnetic Resonance (NMR); Pentose Phosphate Pathway (PPP)