Mistakenly thought to be the consequence of oxygen lack in contracting skeletal muscle we now know that the L-enantiomer of the lactate anion is formed under fully aerobic conditions and is utilized continuously in diverse cells, tissues, organs and at the whole-body level. By shuttling between producer (driver) and consumer (recipient) cells lactate fulfills at least three purposes: 1] a major energy source for mitochondrial respiration; 2] the major gluconeogenic precursor; and 3] a signaling molecule. Working by mass action, cell redox regulation, allosteric binding, and reprogramming of chromatin by lactylation of lysine residues on histones, lactate has major influences in energy substrate partitioning. The physiological range of tissue [lactate] is 0.5-20 mM and the cellular Lactate/Pyruvate ratio (L/P) can range from 10 to >500; these changes during exercise and other stress-strain responses dwarf other metabolic signals in magnitude and span. Hence, lactate dynamics have rapid and major short- and long-term effects on cell redox and other control systems. By inhibiting lipolysis in adipose via HCAR-1, and muscle mitochondrial fatty acid uptake via malonyl-CoA and CPT1, lactate controls energy substrate partitioning. Repeated lactate exposure from regular exercise results in major effects on the expression of regulatory enzymes of glycolysis and mitochondrial respiration. Lactate is the fulcrum of metabolic regulation in vivo.

The “crossover” concept represents a theoretical means by which one can understand the effects of exercise intensity and prior endurance training on the balance of carbohydrate (CHO) and lipid metabolism during sustained exercise. According to the crossover concept, endurance training results in muscular biochemical adaptations that enhance lipid oxidation as well as decrease the sympathetic nervous system responses to given submaximal exercise stresses. These adaptations promote lipid oxidation during mild- to moderate-intensity exercise. In contrast, increases in exercise intensity are conceived to increase contraction-induced muscle glycogenolysis, alter the pattern of fiber type recruitment, and increase sympathetic nervous system activity. Therefore the pattern of substrate utilization in an individual at any point in time depends on the interaction between exercise intensity-induced responses (which increase CHO utilization) and endurance training-induced responses (which promote lipid oxidation). The crossover point is the power output at which energy from CHO-derived fuels predominates over energy from lipids, with further increases in power eliciting a relative increment in CHO utilization and a decrement in lipid oxidation. The contemporary literature contains data indicating that, after endurance training, exercise at low intensities (< or = 45% maximal O2 uptake) is accomplished with lipid as the main substrate. In contrast, the literature also contains reports that are interpreted to indicate that during hard-intensity exercise (approximately 75% maximal O2 uptake) CHO is the predominant substrate. Seen within the context of the crossover concept these apparently divergent results are, in fact, consistent.(ABSTRACT TRUNCATED AT 250 WORDS)