Determinants of Brain Cell Metabolic Phenotypes and Energy Substrate Utilization Unraveled with a Modeling Approach
Figure 4
Model validity tested for different experimental conditions.
(A) Black: r = JMCT/Jglyco = 0.69/0.31 = 2.2 at basal state, as evaluated in vivo by Hyder et al. [28], with physiological values for intracellular lactate (Li) and pyruvate (P) concentrations (0.36 and 0.018 mM, respectively). Le = 1.1 mM. Dark gray: r = JMCT/Jglyco = 0.76/0.24 = 3.2, as observed in vitro by Bouzier-Sore et al. [15], with the experimentally used Le = 1.1 mM. Light gray: Le was increased to 5.5 mM, as described in the experiment by Bouzier-Sore et al. [16], resulting in a higher, but still plausible, value of 0.039 mM for intracellular pyruvate; r = 4.1. White: Same conditions as in light gray, but the glycolytic rate was lowered by 60%, resulting in a lower intracellular pyruvate concentration of 0.036 mM and a JMCT/Jglyco ratio equal to 0.92/0.08 = 11.5, which matches experimental results by Bouzier-Sore et al. [16]. (B) Effect of lactate transport enhancement in the case of a basal JMCT/Jglyco ratio (r) equal to 0.69/0.31 = 2.2, as evaluated in vivo by Hyder et al. [28], cf. black bar in (A). Basal state: Le = 1.1 mM (black). Stimulations: +30% vmax,PDH, +30% kshuttle, +48.5% vmax,glyco (very dark gray, ctrl-bar); +0% Le, +80% vmax,MCT, +70% vmax,PDH, +70% kshuttle (dark gray); +80% Le, +0% vmax,MCT, +70% vmax,PDH, +70% kshuttle (light gray); +80% Le, +80% vmax,MCT, +70% vmax,PDH, +70% kshuttle (white).