Abstract |
Hepatic glucose production and relative Krebs cycle fluxes (indexed to a citrate synthase flux of 1.0) were evaluated with [U-(13)C] glycerol tracer in 5 fed healthy controls and 5 Type 1a glycogen storage disease (GSD1a) patients. Plasma glucose, hepatic glucose-6-phosphate (G6P) and glutamine (13)C-isotopomers were analyzed by (13)C NMR via blood sampling and chemical biopsy. In healthy subjects, 35+/-14% of plasma glucose originated from hepatic G6P while GSD1a patients had no detectable G6P contribution. Compared to controls, GSD1a patients had an increased fraction of acetyl-CoA from pyruvate (0.5+/-0.2 vs. 0.3+/-0.1, p<0.01), and increased pyruvate recycling fluxes (14.4+/-3.8 vs. 8.7+/-2.8, p<0.05). Despite negligible gluconeogenic flux, net anaplerotic outflow was not significantly different from controls (2.2+/-0.8 vs. 1.3+/-0.5). The enrichment of lactate with (13)C-isotopomers derived from the Krebs cycle suggests that lactate was the main anaplerotic product in GSD1a patients.
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Authors | John G Jones, Paula Garcia, Cristina Barosa, Teresa C Delgado, Luisa Diogo |
Journal | Metabolic engineering
(Metab Eng)
Vol. 11
Issue 3
Pg. 155-62
(May 2009)
ISSN: 1096-7184 [Electronic] Belgium |
PMID | 19558966
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Carbon Isotopes
- Lactates
- Glutamine
- Acetyl Coenzyme A
- Pyruvic Acid
- Glucose-6-Phosphatase
- Glucose
- Glycerol
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Topics |
- Acetyl Coenzyme A
(metabolism)
- Adolescent
- Carbon Isotopes
(chemistry)
- Child
- Citric Acid Cycle
(physiology)
- Female
- Gluconeogenesis
(physiology)
- Glucose
(metabolism)
- Glucose-6-Phosphatase
(metabolism)
- Glutamine
(blood)
- Glycerol
(metabolism)
- Glycogen Storage Disease Type I
(metabolism)
- Humans
- Lactates
(blood)
- Liver
(metabolism)
- Male
- Pyruvic Acid
(metabolism)
- Young Adult
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