laktatshuttlet

The laktatshuttlet, commonly called the lactate shuttle, is a concept in physiology that describes how lactate is produced, transported and utilized as an energy source and signaling molecule between and within tissues. It emphasizes that lactate is not merely a waste product of metabolism but a mobile metabolite used by multiple organs.

Mechanism and pathways

During glycolysis, especially in contracting skeletal muscle or under high glycolytic flux, pyruvate is reduced to lactate by the enzyme lactate dehydrogenase (LDH). Lactate is exported from cells via monocarboxylate transporters (MCTs), particularly MCT4 in glycolytic fibers and MCT1 in oxidative fibers. Once in the bloodstream, lactate can be taken up by other tissues, such as the heart, brain, and liver, via MCTs. In those tissues, LDH converts lactate back to pyruvate, feeding the tricarboxylic acid (TCA) cycle for energy production. In the liver, lactate can also be converted to glucose through gluconeogenesis in the Cori cycle. There is also an intracellular shuttle concept, where lactate moves between cytosolic and mitochondrial compartments within a cell to support oxidation.

Physiological significance

The lactate shuttle explains how lactate functions as a rapid energy source during exercise and recovery, and as a substrate for gluconeogenesis and oxidative metabolism in other organs. Training can increase the capacity for lactate production and clearance by upregulating MCTs and mitochondrial enzymes, contributing to a lower lactate threshold and improved endurance. Lactate is also recognized as a signaling molecule that can influence gene expression and adaptation in tissues.

Historical context

The concept was advanced by researchers such as George Brooks, who highlighted the interorgan and intracellular movement of lactate and its role beyond being a mere byproduct of anaerobic metabolism.