The astrocyte-neuron lactate shuttle hypothesis (ANLSH). In this model, glucose is mainly utilized by the astrocyte in glycolysis, and the resulting pyruvate is converted to lactate and released to the extracellular matrix. This lactate is then taken up by the neuron, converted into pyruvate, and utilized in aerobic respiration within the mitochondria. Transport across compartments are shown with dashed arrows. (Please note that the figures are simplified due to space constraints and not all reactions are explicitly included; please refer to Additional File 1 for full set of reactions modeled; numbers in red correspond to the reaction numbers in this file). GLUT, Glucose transporter; MCT, lactate transporter; HK, hexose kinase; PFK, phosphofructo kinase; GAPDH, glyceraldehyde-P-dehydrogenase; PK, pyruvate kinase; LDH, lactate dehydrogenase; AcCoA, Acetyl coenzyme A; a-KG, alpha-ketoglutarate; SucCoA, succinyl coenzyme A; Suc, succinate; Mal, malate; OxAc, oxaloacetate; ATP, adenosine triphosphate; NADH, G6P, glucose-6-phosphate; GAP, glyceraldehyde-3-phosphate; BPG, bisphosphoglycerate; PHase, pyrolyl hydroxylase; HIF, hypoxia-inducible factor; Cr, creatine; P-Cr, phospho-creatine.