Skeletal muscle pyruvate dehydrogenase activity during maximal exercise in humans

Abstract

The regulation of the active form of pyruvate dehydrogenase (PDHa) and related metabolic events were examined in human skeletal muscle during repeated bouts of maximum exercise. Seven subjects completed three consecutive 30-s bouts of maximum isokinetic cycling, separated by 4 min of recovery. Biopsies of the vastus lateralis were taken before and immediately after each bout. PDHa increased from 0.45 +/- 0.15 to 2.96 +/- 0.38, 1.10 +/- 0.11 to 2.91 +/- 0.11, and 1.28 +/- 0.18 to 2.82 +/- 0.32 mmol.min-1.kg wet wt-1 during bouts 1, 2, and 3, respectively. Glycolytic flux was 13-fold greater than PDHa in bouts 1 and 2 and 4-fold greater during bout 3. This discrepancy between the rate of pyruvate production and oxidation resulted in substantial lactate accumulation to 89.5 +/- 11.6 in bout 1, 130.8 +/- 13.8 in bout 2, and 106.6 +/- 10.1 mmol/kg dry wt in bout 3. These events coincided with an increase in the mitochondrial oxidation state, as reflected by a fall in mitochondrial NADH/NAD, indicating that muscle lactate production during exercise was not an O2-dependent process in our subjects. During exercise the primary factor regulating PDHa transformation was probably intracellular Ca2+. In contrast, the primary regulatory factors causing greater PDHa during recovery were lower ATP/ADP and NADH/NAD and increased concentrations of pyruvate and H+. Greater PDHa during recovery facilitated continued oxidation of the lactate load between exercise bouts.

Malonyl-CoA and carnitine in regulation of fat oxidation in human skeletal muscle during exercise

“…In accordance, it has previously been suggested that PDH activity is sensitive to the muscle glycogen level (21,25). PDH activity seems to be important in limiting glycolysis during exercise (24,38,42). In the present study, the high PDH activity during exercise in H-CHO may have, consequently, enhanced glycolytic flux and production of acetyl-CoA from carbohydrate compared with L-CHO (Fig.…”

The acetyl group deficit at the onset of contraction in ischaemic canine skeletal muscle

“…In accordance with previous studies, the infusion of DCA prior to the onset of contraction resulted in near-maximal activation of the PDC to PDCa and acetylation of the free CoASH and carnitine pools to levels reported following maximal exercise (Harris et al 1987;Putman et al 1995;Timmons et al 1997). The increased availability of substrate for the TCA cycle was associated with a reduced reliance upon SLP and an improvement in contractile function during the subsequent rest-to-work transition period, thereby implying that a greater contribution from mitochondrial-derived ATP resynthesis must have occurred to meet the ATP demand of contraction.…”

Chronic low-frequency stimulation upregulates uncoupling protein-3 in transforming rat fast-twitch skeletal muscle

“…Assuming maximal flux through the Krebs cycle and ␤-oxidation (20), it is possible to calculate that the concentration of mitochondrial CoASH would remain above saturating levels for the flux-generating enzymes within those pathways. Furthermore, numerous studies have shown that in normoxia, mitochondria actually become more oxidized and free NAD ϩ concentration increases during contractile activity ranging in intensity from submaximal to maximal (e.g., 14,23,37). The decline in UCP-3 expression observed in human (45,46) and rodent (4) studies further argues against this possibility.…”