Lactate as a fuel for mitochondrial respiration

Lactate production in skeletal muscle has now been studied for nearly two c enturies and still its production and functional role at rest and during mu scle contraction is a subject of debate. Historically, skeletal muscle was seen mainly as the site of lactate production during contraction and lactat e production associated with a lack of muscle oxygenation and fatigue. Late r, it was recognized that skeletal muscle not only plays an important role in lactate production but also in lactate clearance and this in turn has le d to a renewed interest in the metabolic fate of lactate in skeletal muscle and also in other tissues. Studies using lactate isotopes have shown that skeletal muscle extracts lactate from the circulation despite a substantial net lactate release, and that skeletal muscle has a large capacity for lac tate oxidation; these processes being enhanced with exercise. Lactate dehyd rogenase (LDH) controls the formation of lactate and may regulate the turno ver of lactate in the muscle cell. Skeletal muscle contains five LDH isofor ms (LDH1-5). Of the five LDH isoforms, the heart-specific LDH1,2 is general ly suggested to favour the reaction of lactate to pyruvate whereas the musc le-specific LDH4,5 isoform favours lactate formation. However, in this pape r, it is argued that compartmentalization of the muscle cell and LDH associ ation with cell structures may play a more predominant role in whether the LDH reaction proceeds towards lactate or pyruvate formation. The model for skeletal muscle lactate metabolism presented is in essence based on a synth esis of old and more recent studies on skeletal muscle lactate transport, u ptake, release, oxidation, and the role of LDH at rest and during exercise.