lactaatshuttle

The lactate shuttle is a metabolic concept describing the production, transport, and utilization of lactate as an energy substrate and carbon source in mammalian physiology. Proposed to explain how lactate produced in one tissue can be used by another, it highlights lactate as a central intermediate rather than merely a waste product of anaerobic metabolism.

Within cells, the intracellular lactate shuttle describes how lactate produced by glycolysis is transported across the plasma membrane by monocarboxylate transporters (MCTs), primarily MCT1 and MCT4, and then converted back to pyruvate by lactate dehydrogenase (LDH) for entry into the mitochondria and the tricarboxylic acid cycle. This allows cells to rapidly balance redox state and supply energy or biosynthetic precursors. The direction of LDH-catalyzed conversion depends on cellular context and substrate availability.

Intercellularly, the extracellular or intertissue lactate shuttle describes lactate produced by glycolytic tissues being released into the blood and taken up by oxidative tissues, such as heart, slow-twitch skeletal muscle, and the brain, where it can be oxidized or converted to glucose in the liver via gluconeogenesis (the Cori cycle). The lactate transport capacity is influenced by MCT isoforms and their chaperones, such as basigin (CD147).

In the brain, the astrocyte–neuron lactate shuttle concept posits that astrocyte-derived lactate supports neuronal energy metabolism during activity, though the extent and significance of this mechanism remain a topic of ongoing research. Overall, the lactate shuttle framework underscores lactate’s role as a versatile metabolic fuel and signaling molecule across tissues, particularly during exercise and metabolic stress.