FIGURE 3.

The relative contribution of glyceroneogenesis and of glucose by the direct and indirect (via lactate) pathways and its impact on the ¹⁴C/³H ratio of C-1 and C-3 of triglyceride glycerol. The box represents the labeling pattern of G-3-P derived from [¹⁴C]glucose, [³H]pyruvate, and [¹⁴C]lactate. When G-3-P is formed from [¹⁴C]glucose, all the carbons of G-3-P will be equally labeled with ¹⁴C. In contrast, ³H, as a result of equilibrium in the triosephosphate pool (Fig. 2), will appear on C-1 and C-2 and not C-3. G-3-P formed from pyruvate will not have any ¹⁴C label, whereas the hydrogens on C-1, C-2, and C-3 will be completely labeled with ³H. On a stoichiometric equivalent basis, G-3-P formed from 1 molecule of glucose and 2 molecules of pyruvate will have a ¹⁴C/³H ratio on C-1 of 2 ¹⁴C/8 ³H = 0.25 and on C-3 of 2 ¹⁴C/4 ³H = 0.5. ¹⁴C of glucose can also be incorporated into G-3-P via [¹⁴C]lactate. However, as a result of randomization and the exchange of label in the TCA cycle, [¹⁴C]lactate entering the triose phosphate pool will have less label on C-1 relative to C-2 and C-3. Therefore, as the contribution of recycled glucose (via lactate) to G-3-P increases, there will be an increase in the ¹⁴C/³H ratio on C-3 and a decrease of the ratio on C-1. Thus, a high glyceroneogenic flux, relative to glycolytic flux, will result in a high ¹⁴C/³H ratio on C-3 (or C-1 + C-3) as compared with that on C-1. Carbons labeled with ¹⁴C are highlighted in blue, and hydrogens labeled with ³H are highlighted in red. PEP, phosphoenolpyruvate.