FIGURE 1.

The Astrocyte to Neuron Lactate Shuttle. Astrocytes take up glucose from the blood capillaries via glucose transporters (GLUTs). In astrocytes, glucose is either stored as glycogen or metabolized to pyruvate in the glycolysis. Pyruvate is then converted to lactate by the oxidoreductase lactate dehydrogenase (LDH) isoform 5 (LDH5). The lactate is transferred from astrocytes to neurons by the monocarboxylate transporters (MCTs) MCT1, MCT2, and MCT4 in cotransport with a proton. MCT transport activity was found to be facilitated by interaction with the carbonic anhydrases (CAs) CAII and CAIV, which catalyze the equilibrium of H⁺, HCO₃^– and CO₂ both intra- and extracellularly, and by the activity of the electrogenic sodium-bicarbonate cotransporter NBCe1. In neurons, lactate is converted back to pyruvate by LDH1 and transferred into mitochondria for aerobic energy production in the tricarboxylic acid cycle (TCA). In addition, glucose is directly taken up into neurons where it can either serve as energy source in the glycolysis or is shuttled into the pentose phosphate pathway (PPP) for production of NADPH and cellular building blocks like ribose-6-phosphate.