Anaplerosis of the Tricarboxylic Acid Cycle in Human Skeletal Muscle during Exercise

In comparison to cardiac tissue, relatively few data are available regarding the concentrations of tricarboxylic acid cycle intermediates (TCAI) and the potential influence of TCAI pool size on the regulation of cycle flux in mammalian skeletal muscle. However, recent human exercise studies have confirmed the fundamental observation made in electrically-stimulated rodent muscle that moderate to intense contraction results in a net accumulation of TCAI. The increase in TCAI pool size, termed “anaplerosis,” appears exponentially related to work intensity, although the relative changes in the individual cycle intermediates differ markedly. While a number of mechanisms could potentially contribute to the increase in TCAI, the reaction catalyzed by alanine aminotransferase appears primarily responsible for anaplerosis at the onset of exercise in humans. The expansion of the TCAI pool has been suggested to be important for aerobic energy provision, and various theories have been proposed which link the total concentration of TCAI with the capacity for TCA cycle flux during exercise. However, despite the recent advances which have been made with regard to the magnitude and potential source of TCAI expansion in humans, our understanding of the physiological significance of anaplerosis is limited. Indeed, it remains speculative whether the increase in TCAI pool size represents an important regulatory signal or is simply a consequence of the huge increase in metabolic flux which occurs during exercise.