Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle

Abstract

The aims of the present study were twofold: first to investigate whether TCA cycle intermediate (TCAI) pool expansion at the onset of moderate-intensity exercise in human skeletal muscle could be enhanced independently of pyruvate availability by ingestion of glutamine or ornithine alpha-ketoglutarate, and second, if it was, whether this modification of TCAI pool expansion had any effect on oxidative energy status during subsequent exercise. Seven males cycled for 10 min at approximately 70% maximal O2) uptake 1 h after consuming either an artificially sweetened placebo (5 ml/kg body wt solution, CON), 0.125 g/kg body wt L-(+)-ornithine alpha-ketoglutarate dissolved in 5 ml/kg body wt solution (OKG), or 0.125 g/kg body wt L-glutamine dissolved in 5 ml/kg body wt solution (GLN). Vastus lateralis muscle was biopsied 1 h postsupplement and after 10 min of exercise. The sum of four measured TCAI (SigmaTCAI; citrate, malate, fumarate, and succinate, approximately 85% of total TCAI pool) was not different between conditions 1 h postsupplement. However, after 10 min of exercise, SigmaTCAI (mmol/kg dry muscle) was greater in the GLN condition (4.90 +/- 0.61) than in the CON condition (3.74 +/- 0.38, P < 0.05) and the OKG condition (3.85 +/- 0.28). After 10 min of exercise, muscle phosphocreatine (PCr) content was significantly reduced (P < 0.05) in all conditions, but there was no significant difference between conditions. We conclude that the ingestion of glutamine increased TCAI pool size after 10 min of exercise most probably because of the entry of glutamine carbon at the level of alpha-ketoglutarate. However, this increased expansion in the TCAI pool did not appear to increase oxidative energy production, because there was no sparing of PCr during exercise.

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

“…Wagenmakers, 1998Wagenmakers, , 1999, although we are aware of no direct evidence to support them. Indeed, two recent studies demonstrated that altering the extent of TCAI expansion during the rest-work transition does not affect aerobic energy provision (Bruce et al 2001;Gibala et al 2002). These findings are consistent with an alternative explanation for anaplerosis; namely, 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, we are aware of no direct evidence to support this hypothesis, and only recently have attempts been made to manipulate the concentrations of TCAIs during exercise and determine the effect on skeletal muscle metabolism (Bruce et al 2001;Gibala et al 2002). The results from these recent studies have failed to support the notion that an increase in [TCAI] during the rest-work transition is rate limiting for the increase in aerobic energy provision.…”

“…that changes in [TCAI] during exercise reflect alterations in carbon flux into and out of the TCA cycle but are not causally related to TCA cycle turnover (Gibala et al 1998;Constantin-Teodosiu et al 1999). Nonetheless, these recent studies (Bruce et al 2001;Gibala et al 2002) only addressed the initial phase of exercise, when several factors other than [TCAI] may be rate-limiting for the increase in mitochondrial respiration (for review, see Tchakovksy & Hughson, 1999).…”

“…However there is a paucity of data regarding the time course for changes in [TCAI] during a prolonged bout of exercise. Almost all studies have quantified changes in [TCAI] during the first 15 min of exercise at a given work intensity ( Sahlin et al 1995;Gibala et al 1997aGibala et al , 1998Gibala & Saltin, 1999;Bruce et al 2001), or made comparisons between rest and the end of exercise (Spencer et al , 1992Gibala et al 1999). The results of one study showed that the [TCAI] after 40 min of exercise was low compared to 5 min of excercise and not different at exhaustion (Sahlin et al 1990), but the authors primarily focused on fatigue and did not consider the possibility that decreases in [TCAI] might occur relatively early during exercise following an initial expansion of the pool of TCAIs.…”

Effects of glutamine and hyperoxia on pulmonary oxygen uptake and muscle deoxygenation kinetics

“…Indeed, recent studies have shown dissociation between the TCAi pool size and oxidative energy provision (Bruce et al 2001;Gibala et al 2002;Dawson et al 2003Dawson et al , 2005Howarth et al 2004). These studies have however relied upon the analysis of muscle samples taken after a minimum of 5 min of exercise, rather than a time-course of changes during the transition phase of oxidative metabolism (2-3 min; Whipp et al 1982).…”