Role of glucose and glutamine synthesis in the differential recovery of 13CO2 from infused [2-13C] versus [1-13C] acetate.
Carbon exchange in the Krebs cycle may result in underestimation of substrate oxidation measured with 13C-labeled substrates, since carbon labeled in position 2 of acetyl-coenzyme A (CoA) could be incorporated into glucose (via gluconeogenesis) and glutamine. Five healthy volunteers were therefore infused with [1-13C] and [2-13C] acetate at a rate of 0.5 micromol x kg(-1) x min(-1) for 165 minutes on two different occasions in randomized order. Whole body acetate turnover did not differ between the two tracers: 7.9+/-0.3 and 7.5+/-0.6 micromol x kg(-1) x min(-1) (nonsignificant [NS]) for [1-13C] and [2-13C] acetate, respectively. Isotopic 13C enrichment was higher in expired CO2 (0.177+/-0.021 v 0.089+/-0.009 atom percent excess [APE], P < .01) and lower in glucose (0.074+/-0.017 v0.291+/-0.061 mole percent excess [MPE], P < .01) for [1-13C] acetate compared with [2-13C] acetate, respectively, at the end of the infusions. Glutamine isotopic enrichment was slightly but not significantly higher when infusing [1-13C] acetate versus [2-13C] acetate (0.348+/-0.038 v0.495+/-0.069 MPE, NS, respectively). At the end of the experiment, the recovery of 13CO2 from [1-13C] acetate was 44.8%+/-2.7%, and from [2-13C] acetate, 22.6%+/-1.3%. A significant correlation was observed between the differences in 13C enrichment of CO2 for the two tracers and glucose (deltaCO2=0.424 x deltaglucose + 0.001, R2=.9856, P=.0007) or glutamine (deltaCO2=0.621 x deltaglutamine + 0.004, R2=.9573, P=.0038) during the infusion. These results suggest that (1) although gluconeogenesis appears to be more responsible than glutamine for the differential recovery of [2-13C] versus [1-13C] acetate, other secondary pathways are probably also implicated; and (2) different recovery correction factors should be applied when measuring substrate oxidation with a stable isotope tracer depending on the expected position of 13C in acetyl-CoA.
Pouteau
E
E
Human Nutrition Research Center, Metabolism Division, Centre Hopital Universitaire, Nantes, France.
Maugère
P
P
Darmaun
D
D
Marchini
J S
JS
Piloquet
H
H
Dumon
H
H
Nguyen
P
P
Krempf
M
M
D000085:Acetates / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics*; D000328:Adult; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002245:Carbon Dioxide / Q000378:metabolism*; D002247:Carbon Isotopes; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D005943:Gluconeogenesis / Q000502:physiology; D005947:Glucose / Q000502:physiology*; D005973:Glutamine / Q000096:biosynthesis* / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D016014:Linear Models; D008297:Male; D013997:Time Factors
D000085:Acetates; D001786:Blood Glucose; D002247:Carbon Isotopes; D005973:Glutamine; D002245:Carbon Dioxide; D005947:Glucose