Pyruvate shuttling during rest and exercise before and after endurance training in men

Abstract

We describe the isotopic exchange of lactate and pyruvate after arm vein infusion of [3-(13)C]lactate in men during rest and exercise. We tested the hypothesis that working muscle (limb net lactate and pyruvate exchange) is the source of the elevated systemic lactate-to-pyruvate concentration ratio (L/P) during exercise. We also hypothesized that the isotopic equilibration between lactate and pyruvate would decrease in arterial blood as glycolytic flux, as determined by relative exercise intensity, increased. Nine men were studied at rest and during exercise before and after 9 wk of endurance training. Although during exercise arterial pyruvate concentration decreased to below rest values (P < 0.05), pyruvate net release from working muscle was as large as lactate net release under all exercise conditions. Exogenous (arterial) lactate was the predominant origin of pyruvate released from working muscle. With no significant effect of exercise intensity or training, arterial isotopic equilibration [(IE(pyruvate)/IE(lactate)).100%, where IE is isotopic enrichment] decreased significantly (P < 0.05) from 60 +/- 3.1% at rest to an average value of 12 +/- 2.7% during exercise, and there were no changes in femoral venous isotopic equilibration. These data show that 1). the isotopic equilibration between lactate and pyruvate in arterial blood decreases significantly during exercise; 2). working muscle is not solely responsible for the decreased arterial isotopic equilibration or elevated arterial L/P occurring during exercise; 3). working muscle releases similar amounts of lactate and pyruvate, the predominant source of the latter being arterial lactate; 4). pyruvate clearance from blood occurs extensively outside of working muscle; and 5). working muscle also releases alanine, but alanine release is an order of magnitude smaller than lactate or pyruvate release. These results portray the complexity of metabolic integration among diverse tissue beds in vivo.

Exercise tames the wild side of the Myc network: a hypothesis

“…Nominal arterial lactate concentration is 1 mM and is typically higher in the venous effluent of resting muscle due to ongoing glycolysis (12,87). As well, lactate is highly soluble in body water and rapidly transits cell membranes via a family of monocarboxylate transport (i.e., MCT) proteins that are expressed in plasma (28,30,61,85,196), mitochondrial (28,30,35,61,82,83,85), and peroxisome membranes (138).…”

“…In contrast, IL-6 exists in nanomolar or picomolar concentrations, is released from muscle by unknown mechanisms, and circulates bound to plasma proteins. During physical exercise, lactate concentration can exceed 10 mM, and the lactate/ pyruvate ratio can exceed 100 during vigorous exercise (87). Furthermore, it is clear that the concentrations of lactate and pyruvate can change as blood courses through metabolically active tissues, reflecting an interplay between cell metabolism and substrate delivery in the signaling process (101,102).…”

Reply to letter “Pyruvate metabolism in working human skeletal muscle” by Henderson et al.

“…This was based on existing literature, which showed that the majority of 3-carbon-unit release from exercising muscle was lactate, with concurrent pyruvate release being minor in comparison (1,2,7,9). However, after reading the 2004 Henderson et al paper (5) with much interest, which reported that working muscles released the same amount of lactate and pyruvate, we decided that both metabolites must be measured in order to get an accurate estimate of total carbohydrate-derived 3-carbon-unit release across the exercising muscle. However, contrary to Henderson et al (5), we found nearly a fivefold greater net lactate release during exercise compared with pyruvate release.…”

“…When one methodically studies the paper from Henderson et al (5), and their related paper that was published five years earlier (3), it becomes apparent that there are several ambiguous statements regarding the time course of their pyruvate and lactate release data, and there appear to be several methodological errors. First, since there are fluid shifts occurring between muscle and the vascular space during exercise, plasma protein, hemoglobin, and hematocrit are often used to provide a measure of relative changes in intravascular volume when applying the Fick equation.…”

“…In fact, a hematocrit correction can cause such a disparity in the data that some refuse to accept that the hematocrit correction has any validity whatsoever as a measure of change in plasma volume (4). Second, when their two papers are closely examined (3,5), it becomes apparent that pyruvate was measured in whole blood whereas lactate was measured in the plasma. To our knowledge, there are no data examining compartmental distribution of pyruvate.…”