Dissociation between muscle tricarboxylic acid cycle pool size and aerobic energy provision during prolonged exercise in humans

Abstract

It has been suggested that a decrease in the total concentration of tricarboxylic acid cycle intermediates (TCAIs) ‐ secondary to a reduction in glycogen availability ‐ compromises oxidative energy provision in skeletal muscle during prolonged exercise. However, no study has directly tested this hypothesis. We therefore studied six men (28 ± 2 years) during 90 min of leg kicking exercise at an intensity equivalent to 70 % of maximum. Biopsies (vastus lateralis) were obtained at rest and after 5, 10, 15, 30, 60 and 90 min of exercise, and thigh oxygen uptake (VO2,thigh) was calculated according to the Fick principle. The sum of six measured TCAIs (≈95 % of total pool size) was 1.30 ± 0.15 mmol (kg dry wt)−1 at rest and increased (P≤ 0.05) rapidly during exercise to a peak value of 3.15 ± 0.23 mmol (kg dry wt)−1 after 10 min. Thereafter, the [TCAI] declined to 2.14 ± 0.23, 1.73 ± 0.32 and 1.62 ± 0.10 mmol (kg dry wt)−1 after 30, 60 and 90 min, respectively (P≤ 0.05vs.10 min). Despite the 50 % decrease in [TCAI], aerobic energy provision was not compromised, as evidenced by stable VO2,thigh values throughout the entire exercise bout and little change in muscle [phosphocreatine] after 10 min. The largest decrease in [TCAI] (Δ+ 1.00 ± 0.24 mmol (kg dry wt)−1) occurred from 10 to 30 min of exercise despite the fact that muscle [glycogen] remained relatively high at this point in exercise (≈274 ± 24 mmol (kg dry wt)−1 after 30 min; ≈65 % of rest value). Conversely, there was little change in [TCAI] during the final 30 min of exercise (Δ+ 0.11 ± 0.29 mmol (kg dry wt)−1) despite a decrease in [glycogen] to ≈72 ± 3 mmol (kg dry wt)−1 after 90 min (≈13 % of rest value). We conclude that there is a progressive decrease in muscle [TCAI] during prolonged exercise in humans; however this decrease does not compromise aerobic energy provision and is not attributable to the depletion of muscle [glycogen].

Carbohydrate metabolism during prolonged exercise and recovery: interactions between pyruvate dehydrogenase, fatty acids, and amino acids

“…Previous work has shown that glutamine, alanine, and BCAA are the predominant amino acids released from muscle during 60 -90 min of exercise (5,10,21,32). In the present study, ϳ36 mmol/leg were released collectively in the form of glutamine, alanine, BCAA, and ammonia during low-intensity exercise, where glutamine and alanine alone represented ϳ68% of TAA released.…”

“…Glutamate, alanine, and glutamine net exchanges were subsequently reduced (85, 56, and 54%, respectively) from 1 to 2 h of exercise, suggesting that these amino acids were most dynamic in the first hour of exercise. The potential importance of alanine in early exercise is supported by observations from Gibala et al (10,11), where muscle pyruvate and alanine concentrations as well as alanine flux were elevated as early as 5 min of exercise. Thus these data indicate that glutamate, glutamine, and alanine are distinctly linked to pyruvate metabolism and may be important in early exercise regulation.…”

No effect of glutamine supplementation and hyperoxia on oxidative metabolism and performance during high-intensity exercise

“…The present experimental protocol was designed to replicate as closely as possible that of Bruce et al (2001) whilst inserting a period of high intensity exercise. The study by Bruce et al (2001) demonstrated a glutamine-induced enhanced expansion of the TCA intermediate (Gibala et al 1997) but decreases between 10 and 15 min exercise (Gibala et al 2002a). Hence the present protocol was designed to maximise TCA intermediate pool size throughout the period of the time-trial.…”

“…Conversely dissociation between the TCA intermediate pool size and oxidative energy provision during exercise has been consistently demonstrated during sub-maximal exercise (Bruce et al, 2001;Gibala, Gonzalez-Alonso & Saltin, 2002a;Gibala, Peirce, Constantin-Teodosiu & Greenhaff, 2002b;Dawson, Howarth, Tarnopolsky, Wong & Gibala, 2003;Howarth, LeBlanc, Heigenhauser & Gibala, 2004;Timmons, Constantin-Teodosiu, Poucher & Greenhaff, 2004;Dawson, Baker, Greenhaff & Gibala, 2005;Bangsbo, Gibala, Howart & Krustrup, 2006). However, Gibala, MacLean, Graham & Saltin, (1998) Dichloroacetate infusion results in near-maximal activation of the pyruvate dehydrogenase complex and stockpiling of acetyl-units.…”

Regulação metabólica e produção de espécies reativas de oxigênio durante a contração muscular: efeito do glicogênio na manutenção do estado redox intracelular

“…Ao passo que, em indivíduos com conteúdo de glicogênio elevado, observou-se um aumento na formação de intermediários do ciclo de Krebs. Apesar dessas observações, alguns estudos não conseguiram demonstrar esse efeito do aumento dos estoques de glicogênio na performance e no conteúdo de intermediários do ciclo de Krebs (50)(51)(52) . O glicogênio é o principal substrato da vias das pentoses, como já mencionado, uma via importante de fornecimento de NADPH/glutationa para o sistema glutationa redutase/peroxidase na manutenção do estado redox intracelular (15,23,32) , sugerindo que uma menor disponibilidade de glicogênio poderia ainda comprometer a síntese de glutationa, reduzindo a capacidade de defesa antioxidante do músculo esquelético durante contrações prolongadas.…”