ROLE OF GLUCOSE AND GLUTAMINE SYNTHESIS IN THE DIFFERENTIAL RECOVERY OF (CO2)-C-13 FROM INFUSED [2-C-13] VERSUS [1-C-13] ACETATE

Carbon exchange in the Krebs cycle may result in underestimation of su bstrate oxidation measured with C-13-labeled substrates, since carbon labeled in position 2 of acetyl-coenzyme A (CoA) could be incorporated into glucose (via gluconeogenesis) and glutamine. Five healthy volunt eers were therefore infused with [1-C-13] and [2-C-13] acetate at a ra te of 0.5 mu mol . kg(-1) . min(-1) for 165 minutes on two different o ccasions in randomized order. Whole body acetate turnover did not diff er between the two tracers: 7.9 +/- 0.3 and 7.5 +/- 0.6 mu mol . kg(-1 ) . min(-1) (nonsignificant [NS]) for [1-C-13] and [2-C-13] acetate, r espectively. Isotopic C-13 enrichment was higher in expired CO2 (0.177 +/- 0.021 v 0.089 +/- 0.009 atom percent excess [APE], P <.01) and lo wer in glucose (0.074 +/- 0.017 v 0.291 +/- 0.061 mole percent excess [MPE], P <.01) for [1-C-13] acetate compared with [2-C-13] acetate, re spectively, at the end of the infusions. Glutamine isotopic enrichment was slightly but not significantly higher when infusing [1-C-13] acet ate versus [2-C-13] acetate (0.348 +/- 0.038 v 0.495 +/- 0.069 MPE, NS , respectively). At the end of the experiment, the recovery of (CO2)-C -13 from [1-C-13] acetate was 44.8% +/- 2.7%, and from [2-C-13] acetat e, 22.6% +/- 1.3%. A significant correlation was observed between the differences in C-13 enrichment of CO2 for the two tracers and glucose (Delta CO2 = 0.424 . Delta glucose + 0.001, R-2 =.9856, P =.0007) Or g lutamine (Delta CO2 = 0.621 . Delta glutamine + 0.004, R-2 =.9573, P = .0038) during the infusion. These results suggest that (1) although gl uconeogenesis appears to be more responsible than glutamine for the di fferential recovery of [2-C-13] versus [1-C-13] acetate, other seconda ry pathways are probably also implicated; and (2) different recovery c orrection factors should be applied when measuring substrate oxidation with a stable isotope tracer depending on the expected position of C- 13 in acetyl-CoA. Copyright (C) 1998 by W.B. Saunders Company.