Fig. 1

Metabolic water is produced in different pathways of glucose metabolism. CMRglc represents the glucose utilization rate, as determined at the hexokinase step. The CMRglc-ox represents the rate of glucose oxidation, which is equivalent to half of the TCA cycle rate when all glucose is oxidized. This is because the cycle rate is twice that of CMRglc, with two pyruvate molecules produced per glucose molecule. The glycolytic pathway, the electron transport chain, and oxidative phosphorylation are the sources of metabolic water, which is produced and indicated by a plus sign. Conversely, the TCA cycle and cytosolic energy-dependent reactions that utilize hydrolysis consume metabolic water, indicated by a minus sign. The efflux of water across the mitochondrial membrane is significantly greater than the influx of pyruvate. Most of the water produced by the electron transport chain and oxidative phosphorylation is released to the cytosol, where it can be utilized for hydrolytic reactions or secreted into interstitial fluid. This flux is continuous, directional, and varies in accordance with the rate of glucose oxidation. For further details, please refer to Appendix Sects. "Reactions that consume and produce water during metabolism of glucose" and "Metabolic water during metabolism of Glc-6P via branch pathways", Fig. 8, and Table 2