FIGURE 3.

Lactate and glutamine metabolism. Overview of lactate and glutamine metabolism. Glucose is imported by GLUT1 transporter. Glucose is then metabolized by glycolysis into pyruvate. Pyruvate then either enters the TCA cycle through pyruvate dehydrogenase (PDH) for ATP and biomolecule synthesis, or pyruvate is converted to lactate by lactate dehydrogenase (LDH). Lactate is then exported by MCT4 lactate exporter. Extracellular lactate can be imported by MCT1 and converted to pyruvate by lactate dehydrogenase for utilization in the TCA cycle for ATP and biomolecule synthesis. Glutamine is imported by ASCT2 where it then enters the mitochondria and is converted to glutamate. Glutamate can either enter the TCA cycle or is converted to GSH for ROS neutralization. Under metabolic stress conditions, the LKB1-AMPK pathway is activated. LKB1 activates AMPK which inhibits ACC and mTORC1. AMPK inhibition of ACC prevents lipid synthesis and mTORC1 inhibition by AMPK reduces glycolysis. Low glycolysis rate reduces TCA cycle generation of citrate which is used to generate acetyl-CoA for lipid synthesis.