Determinants of Brain Cell Metabolic Phenotypes and Energy Substrate Utilization Unraveled with a Modeling Approach
Figure 1
Model describing the simplified energetics of brain cells.
Glucose undergoes glycolysis and all resulting pyruvate is either further metabolized by PDH or converted to lactate by LDH before being transported out of the cell. On the other hand, lactate can be transported into the cell and then metabolized into pyruvate by LDH. Because these processes require NAD+/NADH, we also modeled the “recycling" shuttle of NADH to NAD+ by mitochondria. The red arrow shows the metabolism of a typical predominantly glycolytic cell, characterized by lactate export; the blue arrow shows a typical oxidative phenotype, where both glucose and lactate import contribute to oxidative phosphorylation. Abbreviations: Le, extracellular lactate; Li, intracellular lactate; P, pyruvate; NADH, reduced nicotinamide-adenine dinucleotide; Glc, glucose; JMCT, transmembrane flux of lactate via MCTs; Jshuttle, flux of NADH to NAD+ “recycling" by the mitochondria; Jglyco, glycolytic flux; JLDH, metabolic flux via LDH; JPDH, metabolic flux via PDH.