Regulation of skeletal muscle glycogen phosphorylase and PDH during maximal intermittent exercise

Abstract

The time course for the activation of glycogen phosphorylase (Phos) and pyruvate dehydrogenase (PDH) and their allosteric regulators was determined in human skeletal muscle during repeated bouts of maximal exercise. Six subjects completed three 30-s bouts of maximal isokinetic cycling separated by 4-min recovery periods. Muscle biopsies were taken at rest and at 6, 15, and 30 s of exercise during bouts 1 and 3. Phos was rapidly activated within the first 6 s of bout 1 from 12% at rest to 47% at 6 s. The activation of PDH increased from 14% at rest to 48% at 6 s and 95% at 15 s of bout 1. Phos reverted back to basal values at the end of the first bout, whereas PDH remained fully activated. In contrast, in the third bout, PDH was 42% at rest and was activated more rapidly and was nearly completely activated by 6 s, whereas Phos remained at basal levels (range 14-20%). Lactate accumulation was marked in the first bout and increased progressively from 2.7 to 76.1 mmol/kg dry wt with no further increase in bout 3. Glycogen utilization was also marked in the first bout and was negligible in bout 3. The rapid activation of Phos and slower activation of PDH in bout 1 was probably due to Ca(2+) release from the sarcoplasmic reticulum. Lactate accumulation appeared to be due to an imbalance of the relative activities of Phos and PDH. The increase in H(+) concentration may have served to reduce pyruvate production by inhibiting Phos transformation and may have simultaneously activated PDH in the third bout such that there was a better matching between pyruvate production and oxidation and minimal lactate accumulation. As each bout progressed and with successive bouts, there was a decreasing ability to stimulate substrate phosphorylation through phosphocreatine hydrolysis and glycolysis and a shift toward greater reliance on oxidative phosphorylation.

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT)

“…Whilst with moderate aerobic exercise the rate of glycogenolysis will be matched closely with glucose oxidation, the considerable amount of glucose-6-phosphate released from glycogenolysis in the early stages of the initial REHIT sprint is likely to pose a substantial challenge to the intramyocellular milieu. Although the glycolytic catabolism of glucose-6-phosphate results in a rapid accumulation of pyruvate, only a small fraction of this is immediately oxidised; most is instead converted to lactate (Parolin et al 1999), as evidenced by the large spike in plasma lactate concentration observed in our study. The strong reliance on glycolysis for ATP resynthesis will also result in a reduction in both intramyocellular and blood pH levels (Robergs et al 2004).…”

“…3-4 x 30 s) sprint efforts (Parolin et al 1999;Gibala et al 2009). This finding is supported by the data of Parolin et al (1999) who demonstrated that during three repeated 30-s all-out cycle sprints glycogen phosphorylase (and hence glycogenolysis) is predominantly activated during the first 15 s of the first sprint, and that further sprints break down little or no extra glycogen.…”

“…The subsequent drop in RER below 0.70 reflects the retention of CO2 to replenish the depleted blood bicarbonate stores during recovery (Laforgia et al 1997). Given that the majority of glycogenolysis, and hence metabolic acidosis, occurs during the first sprint of a repeated sprint protocol (Parolin et al 1999) it is not surprising that a protocol involving a smaller number of shorter sprints poses a similar challenge to buffering mechanisms compared with more strenuous HIT protocols, and hence still has this effect on RER (Hazell et al 2012;Chan and Burns 2013). It can be speculated that this regular overloading (and recovery) of muscle and blood buffering mechanisms provides an explanation for the adaptations in buffering capacity observed following six weeks of HIT (Gibala et al 2006).…”

“…At the molecular level, adaptation to exercise is thought to result from cumulative transient increases in gene transcription (and protein synthesis) that follow each acute exercise bout, with the metabolic perturbations induced by contraction activating various signalling kinases which, in turn, target downstream transcriptional coactivators and regulators (Perry et al 2010). Previous studies investigating more time-consuming and more strenuous HIT protocols have demonstrated a molecular response which includes a 20-30% drop in muscle glycogen concentrations, substantial lactate accumulation, an altered ATP:ADP ratio, and increases in AMPK activity (1.4-fold), p38 MAPK activity (1.5-fold), and a 6-fold increase in mRNA expression of PGC1α (Esbjornsson-Liljedahl et al 1999;Gibala et al 2009;Parolin et al 1999). Furthermore, the acute disturbance in muscle metabolism is associated with a substantial disruption of wholebody/systemic homeostasis, including a prolonged increase in post-exercise oxygen consumption (EPOC), and alterations in the appetite regulating hormones acylated ghrelin and peptide YY in a direction which would be expected to suppress appetite (Hazell et al 2012;Williams et al 2013;Deighton et al 2013).…”

“…In the first study we measured glycogen degradation, AMPK and p38 MAPK activation, and changes in PGC1α and GLUT4 gene expression in skeletal muscle following REHIT. Given that glycogen utilisation appears to be most prominent during the first 15-s of the first sprint during a repeated sprint protocol (Parolin et al 1999), and glycogen concentrations appear to play an important role in the regulation of AMPK and p38 MAPK (Philp et al 2012), we hypothesised that REHIT would be associated with a 20-30% reduction in muscle glycogen, activation of AMPK and p38 MAPK, and increases in GLUT4 and PGC1α gene expression. In study 2, we examined differences between REHIT and a bout of moderate-intensity aerobic exercise in a range of post-exercise physiological responses including oxygen consumption and appetite regulating hormones.…”