Estimating gluconeogenesis with [U-13C]glucose: molecular condensation requires a molecular approach

Recently three equations for estimating gluconeogenesis in vivo have been proposed, two by J. A. Tayek and J. Katz [Am. J. Physiol. 270 (Endocrinol. Metab. 33): E709-E717, 1996, and Am. J. Physiol. 272 (Endocrinol. Metab. 35): E476-E484, 1997] and one by B. R. Landau, J. Wahren, K. Ekberg, S. F. Previs, D. Yang, and H. Brunengraber [Am. J. Physiol. 274 (Endocrinol. Metab. 37): E954-E961, 1998]. Both groups estimate gluconeogenesis from cycling of [U-13C]glucose to lactate and back to glucose, detected by mass spectrometry. Landau's approach is based on analysis of labeled molecules, whereas Tayek and Katz's is based on labeling of carbon atoms by use of the concept of "molar enrichment," which weights each mass isotopomer by the number of labeled carbons. We derived an equation very similar to Landau's using binomial probability. Our analysis demonstrates that the molecular-based approach is correct. Additionally, equations appropriate for 14C studies are not appropriate for 13C studies, because the method used to detect 14C, decay of atoms, differs from 13C mass isotopomers detected as labeled molecules. We conclude that the molar enrichment carbon-based approach is not useful in the derivation of equations for the polymerization of molecules detected by mass spectrometry of molecules, and we confirm the findings of Landau et al.