title: An integrated (2)H and (13)C NMR study of gluconeogenesis and TCA cycle flux in humans.
abstract: Hepatic glucose synthesis from glycogen, glycerol, and the tricarboxylic acid (TCA) cycle was measured in five overnight-fasted subjects by (1)H, (2)H, and (13)C NMR analysis of blood glucose, urinary acetaminophen glucuronide, and urinary phenylacetylglutamine after administration of [1,6-(13)C(2)]glucose, (2)H(2)O, and [U-(13)C(3)]propionate. This combination of tracers allows three separate elements of hepatic glucose production (GP) to be probed simultaneously in a single study: 1) endogenous GP, 2) the contribution of glycogen, phosphoenolpyruvate (PEP), and glycerol to GP, and 3) flux through PEP carboxykinase, pyruvate recycling, and the TCA cycle. Isotope-dilution measurements of [1,6-(13)C(2)] glucose by (1)H and (13)C NMR indicated that GP in 16-h-fasted humans was 10.7 +/- 0.9 micromol.kg(-1).min(-1). (2)H NMR spectra of monoacetone glucose (derived from plasma glucose) provided the relative (2)H enrichment at glucose H-2, H-5, and H-6S, which, in turn, reflects the contribution of glycogen, PEP, and glycerol to total GP (5.5 +/- 0.7, 4.8 +/- 1.0, and 0.4 +/- 0.3 micromol.kg(-1).min(-1), respectively). Interestingly, (13)C NMR isotopomer analysis of phenylacetylglutamine and acetaminophen glucuronide reported different values for PEP carboxykinase flux (68.8 +/- 9.8 vs. 37.5 +/- 7.9 micromol.kg(-1).min(-1)), PEP recycling flux (59.1 +/- 9.8 vs. 27.8 +/- 6.8 micromol.kg(-1).min(-1)), and TCA cycle flux (10.9 +/- 1.4 vs. 5.4 +/- 1.4 micromol.kg(-1).min(-1)). These differences may reflect zonation of propionate metabolism in the liver.
authors.affiliation: Department of Radiology, University of Texas Southwestern Medical Center, Dallas 75235, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Jones
authors.forename: M A
authors.initials: MA
authors.lastname: Solomon
authors.forename: S M
authors.initials: SM
authors.lastname: Cole
authors.forename: A D
authors.initials: AD
authors.lastname: Sherry
authors.forename: C R
authors.initials: CR
authors.lastname: Malloy
mesh_terms: D000082:Acetaminophen / Q000031:analogs & derivatives* / Q000652:urine; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism*; D002247:Carbon Isotopes; D002952:Citric Acid Cycle; D003903:Deuterium; D005260:Female; D005943:Gluconeogenesis; D005947:Glucose / Q000378:metabolism*; D005973:Glutamine / Q000031:analogs & derivatives* / Q000652:urine; D006801:Humans; D006859:Hydrogen; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008954:Models, Biological; D010728:Phosphoenolpyruvate / Q000378:metabolism; D011422:Propionates / Q000378:metabolism; D012016:Reference Values; D013997:Time Factors; D014867:Water / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D002247:Carbon Isotopes; D008112:Liver Glycogen; D011422:Propionates; D014867:Water; D005973:Glutamine; D000082:Acetaminophen; D010728:Phosphoenolpyruvate; D006859:Hydrogen; C037386:acetaminophen glucuronide; C003089:phenylacetylglutamine; D003903:Deuterium; D005947:Glucose