Abstract
The aim of the present study was to determine whether glutamine ingestion, which has been shown to enhance the exercise-induced increase in the tricarboxylic acid intermediate (TCAi) pool size, resulted in augmentation of the rate of increase in oxidative metabolism at the onset of exercise. In addition, the potential interaction with oxygen availability was investigated by completing exercise in both normoxic and hyperoxic conditions. Eight male cyclists cycled for 6 min at 70% \( \mathop V\limits^\cdot {\text{O}}_{2\max } \) following consumption of a drink (5 ml kg body mass−1) containing a placebo or 0.125 g kg body mass−1 of glutamine in normoxic (CON and GLN respectively) and hyperoxic (HYP and HPG respectively) conditions. Breath-by-breath pulmonary oxygen uptake and continuous, non-invasive muscle deoxygenation (via near infrared spectroscopy: NIRS) data were collected throughout exercise. The time constant of the phase II component of pulmonary oxygen uptake kinetics was unchanged between trials (CON: 21.5 ± 3.0 vs. GLN: 18.2 ± 1.3 vs. HYP: 18.9 ± 2.0 vs. HPG: 18.6 ± 1.2 s). There was also no alteration of the kinetics of relative muscle deoxygenation as measured via NIRS (CON: 5.9 ± 0.7 vs. GLN: 7.3 ± 0.8 vs. HYP: 6.5 ± 0.9 vs. HPG: 5.2 ± 0.4 s). Conversely, the mean response time of pulmonary oxygen uptake kinetics was faster (CON: 33.4 ± 1.2 vs. GLN: 29.8 ± 2.3 vs. HYP: 33.2 ± 2.6 vs. HPG: 31.6 ± 2.6 s) and the time at which muscle deoxygenation increased above pre-exercise values was earlier (CON: 9.6 ± 0.9 vs. GLN: 8.7 ± 1.1 vs. HYP: 8.5 ± 0.8 vs. HPG: 8.4 ± 0.7 s) following glutamine ingestion. In normoxic conditions, plasma lactate concentration was lower following glutamine ingestion compared to placebo. Whilst the results of the present study provide some support for the present hypothesis, the lack of any alteration in the time constant of pulmonary oxygen uptake and muscle deoxygenation kinetics suggest that the normal exercise induced expansion of the TCAi pool size is not limiting to oxidative metabolism at the onset of cycle exercise at 70% \(\dot V{\rm{O}}_{\rm{2 max}}.\)
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References
Ahmed A, Maxwell DL, Taylor PM, Rennie MJ (1993) Glutamine transport in human skeletal muscle. Am J Physiol 264:E993–E1000
Bangsbo J, Gibala MJ, Krustrup P, Gonzalez-Alonso J, Saltin B (2002) Enhanced pyruvate dehydrogenase activity does not affect muscle O2 uptake at onset of intense exercise in humans. Am J Physiol Regul Integr Comp Physiol 282:R273–R280
Barstow TJ, Mole PA (1987) Simulation of pulmonary O2 uptake during exercise transients in humans. J Appl Physiol 63:2253–2261
Barstow TJ, Buchthal SD, Zanconato S, Cooper DM (1994) Changes in potential controllers of human skeletal muscle respiration during incremental calf exercise. J Appl Physiol 77:2169–2176
Berger NJ, Tolfrey K, Williams AG, Jones AM (2006) Influence of continuous and interval training on oxygen uptake on-kinetics. Med Sci Sports Exerc 38:504–512
Bergmeyer H (1974) Methods of enzymatic analysis. Academic, London
Brown GC (2000) Nitric oxide as a competitive inhibitor of oxygen consumption in the mitochondrial respiratory chain. Acta Physiol Scand 168:667–674
Brown GC (2001) Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta 1504:46–57
Bruce M, Constantin-Teodosiu D, Greenhaff PL, Boobis LH, Williams C, Bowtell JL (2001) Glutamine supplementation promotes anaplerosis but not oxidative energy delivery in human skeletal muscle. Am J Physiol Endocrinol Metab 280:E669–E675
Cadefau J, Green HJ, Cusso R, Ball-Burnett M, Jamieson G (1994) Coupling of muscle phosphorylation potential to glycolysis during work after short-term training. J Appl Physiol 76:2586–2593
Campbell-O’Sullivan SP, Constantin-Teodosiu D, Peirce N, Greenhaff PL (2002) Low intensity exercise in humans accelerates mitochondrial ATP production and pulmonary oxygen kinetics during subsequent more intense exercise. J Physiol 538:931–939. DOI 10.1113/jphysiol.2001.013238
Caputo F, Mello MT, Denadai BS (2003) Oxygen uptake kinetics and time to exhaustion in cycling and running: a comparison between trained and untrained subjects. Arch Physiol Biochem 111:461–466
Dawson KD, Howarth KR, Tarnopolsky MA, Wong ND, Gibala MJ (2003) Short-term training attenuates muscle TCA cycle expansion during exercise in women. J Appl Physiol 95:999–1004. DOI 10.1152/japplphysiol.01118.2002
Dawson KD, Baker DJ, Greenhaff PL, Gibala MJ (2005) An acute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle. J.Physiol 565:637–643. DOI 10.1113/jphysiol.2004.079939
De Blasi RA, Cope M, Elwell C, Safoue F, Ferrari M (1993) Noninvasive measurement of human forearm oxygen consumption by near infrared spectroscopy. Eur J Appl Physiol Occup Physiol 67:20–25
Duncan A, Meek JH, Clemence M, Elwell CE, Tyszczuk L, Cope M, Delpy DT (1995) Optical pathlength measurements on adult head, calf and forearm and the head of the newborn infant using phase resolved optical spectroscopy. Phys Med Biol 40:295–304
Evans MK, Savasi I, Heigenhauser GJ, Spriet LL (2001) Effects of acetate infusion and hyperoxia on muscle substrate phosphorylation after onset of moderate exercise. Am J Physiol Endocrinol Metab 281:E1144–E1150
Fawkner SG, Armstrong N (2004) Sex differences in the oxygen uptake kinetic response to heavy-intensity exercise in prepubertal children. Eur J Appl Physiol 93:210–216. DOI 10.1007/s00421-004-1201-7
Ferrari M, Binzoni T, Quaresima V (1997) Oxidative metabolism in muscle. Philos Trans R Soc Lond B Biol Sci 352:677–683
Fukuoka Y, Grassi B, Conti M, Guiducci D, Sutti M, Marconi C, Cerretelli P (2002) Early effects of exercise training on on- and off-kinetics in 50-year-old subjects. Pflugers Arch 443:690–697. DOI 10.1007/s00424-001-0748-y
Gaesser GA, Poole DC (1996) The slow component of oxygen uptake kinetics in humans. Exerc Sport Sci Rev 24:35–71
Gibala MJ, Tarnopolsky MA, Graham TE (1997) Tricarboxylic acid cycle intermediates in human muscle at rest and during prolonged cycling. Am J Physiol 272:E239–E244
Gibala MJ, Gonzalez-Alonso J, Saltin B (2002) Dissociation between muscle tricarboxylic acid cycle pool size and aerobic energy provision during prolonged exercise in humans. J Physiol 545:705–713. DOI 10.1113/jphysiol.2002.028084
Grassi B, Poole DC, Richardson RS, Knight DR, Erickson BK, Wagner PD (1996) Muscle O2 uptake kinetics in humans: implications for metabolic control. J Appl Physiol 80:988–998
Grassi B, Gladden LB, Samaja M, Stary CM, Hogan MC (1998a) Faster adjustment of O2 delivery does not affect V(O2) on-kinetics in isolated in situ canine muscle. J Appl Physiol 85:1394–1403
Grassi B, Gladden LB, Stary CM, Wagner PD, Hogan MC (1998b) Peripheral O2 diffusion does not affect V(O2)on-kinetics in isolated insitu canine muscle. J Appl Physiol 85:1404–1412
Grassi B, Hogan MC, Greenhaff PL, Hamann JJ, Kelley KM, Aschenbach WG, Constantin-Teodosiu D, Gladden LB (2002) Oxygen uptake on-kinetics in dog gastrocnemius in situ following activation of pyruvate dehydrogenase by dichloroacetate. J Physiol 538:195–207. DOI 10.1113/jphysiol.2001.012984
Grassi B, Pogliaghi S, Rampichini S, Quaresima V, Ferrari M, Marconi C, Cerretelli P (2003) Muscle oxygenation and pulmonary gas exchange kinetics during cycling exercise on-transitions in humans. J Appl Physiol 95:149–158. DOI 10.1152/japplphysiol.00695.2002
Grassi B, Hogan MC, Kelley KM, Howlett RA, Gladden LB (2005) Effects of nitric oxide synthase inhibition by L-NAME on oxygen uptake kinetics in isolated canine muscle in situ. J Physiol 568:1021–1033
Green H, Grant S, Bombardier E, Ranney D (1999) Initial aerobic power does not alter muscle metabolic adaptations to short-term training. Am J Physiol 277:E39–E48
Hankard RG, Darmaun D, Sager BK, D’Amore D, Parsons WR, Haymond M (1995) Response of glutamine metabolism to exogenous glutamine in humans. Am J Physiol 269:E663–E670
Hogan MC (2001) Fall in intracellular PO(2) at the onset of contractions in Xenopus single skeletal muscle fibers. J Appl Physiol 90:1871–1876
Howarth KR, LeBlanc PJ, Heigenhauser GJ, Gibala MJ (2004) Effect of endurance training on muscle TCA cycle metabolism during exercise in humans. J Appl Physiol 97:579–584. DOI 10.1152/japplphysiol.01344.2003
Howlett RA, Heigenhauser GJ, Hultman E, Hollidge-Horvat MG, Spriet LL (1999) Effects of dichloroacetate infusion on human skeletal muscle metabolism at the onset of exercise. Am J Physiol 277:E18–E25
Hughson RL, Cochrane JE, Butler GC (1993) Faster O2 uptake kinetics at onset of supine exercise with than without lower body negative pressure. J Appl Physiol 75:1962–1967
Hughson RL, Kowalchuk JM (1995) Kinetics of oxygen uptake for submaximal exercise in hyperoxia, normoxia, hypoxia. Can J Appl Physiol 20:198–210
Hughson RL, Shoemaker JK, Tschakovsky ME, Kowalchuk JM (1996) Dependence of muscle \( \mathop V\limits^ \cdot {\text{O}}_2 \)on blood flow dynamics at onset of forearm exercise. J Appl Physiol 81:1619–1626
Jones AM, Wilkerson DP, Koppo K, Wilmshurst S, Campbell IT (2003) Inhibition of nitric oxide synthase by L-NAME speeds phase II pulmonary.VO2 kinetics in the transition to moderate-intensity exercise in man. J Physiol 552:265–272. DOI 10.1113/jphysiol.2003.045799
Jones AM, Wilkerson DP, Wilmshurst S, Campbell IT (2004) Influence of L-NAME on pulmonary O2 uptake kinetics during heavy-intensity cycle exercise. J Appl Physiol96:1033–1038. DOI 10.1152/japplphysiol.00381.2003
Joyner MJ, Dietz NM (1997) Nitric oxide and vasodilation in human limbs. J Appl Physiol 83:1785–1796
Kaasik A, Minajeva A, De Sousa E, Ventura-Clapier R, Veksler V (1999) Nitric oxide inhibits cardiac energy production via inhibition of mitochondrial creatine kinase. FEBS Lett 444:75–77
Kilding AE, Winter EM, Fysh M (2006) A comparison of pulmonary oxygen uptake kinetics in middle- and long-distance runners. Int J Sports Med 27:419–426
Knight DR, Schaffartzik W, Poole DC, Hogan MC, Bebout DE, Wagner PD (1993) Effects of hyperoxia on maximal leg O2 supply and utilization in men. J Appl Physiol 75:2586–2594
Koretsky AP, Balaban RS (1987) Changes in pyridine nucleotide levels alter oxygen consumption and extra-mitochondrial phosphates in isolated mitochondria: a 31P-NMR and NAD(P)H fluorescence study. Biochim Biophys Acta 893:398–408
Lamarra N, Whipp BJ, Ward SA, Wasserman K (1987) Effect of interbreath fluctuations on characterizing exercise gas exchange kinetics. J Appl Physiol 62:2003–2012
LeBlanc PJ, Howarth KR, Gibala MJ, Heigenhauser GJ (2004) Effects of 7 wk of endurance training on human skeletal muscle metabolism during submaximal exercise. J Appl Physiol 97:2148–2153. DOI 10.1152/japplphysiol.00517.2004 8750–7587/04
Linnarsson D, Karlsson J, Fagraeus L, Saltin B (1974) Muscle metabolites and oxygen deficit with exercise in hypoxia and hyperoxia. J Appl Physiol 36:399–402
Macdonald M, Pedersen PK, Hughson RL (1997) Acceleration of VO2 kinetics in heavy submaximal exercise by hyperoxia and prior high-intensity exercise. J Appl Physiol 83:1318–1325
Parolin ML, Spriet LL, Hultman E, Hollidge-Horvat MG, Jones NL, Heigenhauser GJ (2000) Regulation of glycogen phosphorylase and PDH during exercise in human skeletal muscle during hypoxia. Am J Physiol Endocrinol Metab 278:E522–E534
Perrey S, Tschakovsky ME, Hughson RL (2001) Muscle chemoreflex elevates muscle blood flow and O2 uptake at exercise onset in nonischemic human forearm. J Appl Physiol 91:2010–2016
Phillips SM, Green HJ, MacDonald MJ, Hughson RL (1995) Progressive effect of endurance training on VO2 kinetics at the onset of submaximal exercise. J Appl Physiol 79:1914–1920
Poole DC, Ward SA, Gardner GW, Whipp BJ (1988) Metabolic and respiratory profile of the upper limit for prolonged exercise in man. Ergonomics 31:1265–1279
Poole DC, Ward SA, Whipp BJ (1990) The effects of training on the metabolic and respiratory profile of high-intensity cycle ergometer exercise. Eur J Appl Physiol Occup Physiol 59:421–429
Prieur F, Busso T, Castells J, Bonnefoy R, Benoit H, Geyssant A, Denis C (1998) Validity of oxygen uptake measurements during exercise under moderate hyperoxia. Med Sci Sports Exerc 30:958–962
Richardson RS, Grassi B, Gavin TP, Haseler LJ, Tagore K, Roca J, Wagner PD (1999) Evidence of O2 supply-dependent VO2 max in the exercise-trained human quadriceps. J Appl Physiol 86:1048–1053
Roberts PA, Loxham SJ, Poucher SM, Constantin-Teodosiu D, Greenhaff PL (2002) The acetyl group deficit at the onset of contraction in ischaemic canine skeletal muscle. J Physiol 544:591–602. DOI 10.1113/jphysiol.2002.021097
Roberts PA, Loxham SJ, Poucher SM, Constantin-Teodosiu D, Greenhaff PL (2005) Acetyl-CoA provision and the acetyl group deficit at the onset of contraction in ischemic canine skeletal muscle. Am J Physiol Endocrinol Metab 288:E327–E334. DOI 10.1152/ajpendo.00441.2003
Rossiter HB, Ward SA, Doyle VL, Howe FA, Griffiths JR, Whipp BJ (1999) Inferences from pulmonary O2 uptake with respect to intramuscular [phosphocreatine] kinetics during moderate exercise in humans. J Physiol 518:921–932
Rossiter HB, Ward SA, Kowalchuk JM, Howe FA, Griffiths JR, Whipp BJ (2002) Dynamic asymmetry of phosphocreatine concentration and O(2) uptake between the on- and off-transients of moderate- and high-intensity exercise in humans. J Physiol 541:991–1002. DOI 10.1113/jphysiol.2001.012910
Sahlin K, Katz A, Broberg S (1990) Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. Am J Physiol 259:C834–C841
Savasi I, Evans MK, Heigenhauser GJF, Spriet LL (2002) Skeletal muscle metabolism is unaffected by DCA infusion and hyperoxia after onset of intense aerobic exercise. Am J Physiol Endocrinol.Metab 283:E108–E115. DOI 10.1152/ajpendo.00337.2001
Sessa WC, Hecker M, Mitchell JA, Vane JR (1990) The metabolism of l-arginine and its significance for the biosynthesis of endothelium-derived relaxing factor: l-glutamine inhibits the generation of L-arginine by cultured endothelial cells. Proc Natl Acad Sci USA 87:8607–8611
Shen W, Xu X, Ochoa M, Zhao G, Wolin MS, Hintze TH (1994) Role of nitric oxide in the regulation of oxygen consumption in conscious dogs. Circ Res 75:1086–1095
Stellingwerff T, Glazier L, Watt MJ, LeBlanc PJ, Heigenhauser GJ, Spriet L.L (2005) Effects of hyperoxia on skeletal muscle carbohydrate metabolism during transient and steady-state exercise. J APPl Physiol 98:250–256
Swierkosz TA, Mitchell JA, Sessa WC, Hecker M, Vane JR (1990) l-glutamine inhibits the release of endothelium-derived relaxing factor from the rabbit aorta. Biochem Biophys Res Commun 172:143–148
Timmons JA, Poucher SM, Constantin-Teodosiu D, Worrall V, Macdonald IA, Greenhaff PL (1996) Increased acetyl group availability enhances contractile function of canine skeletal muscle during ischemia. J Clin Invest 97:879–883
Timmons JA, Poucher SM, Constantin-Teodosiu D, Macdonald IA, Greenhaff PL (1997) Metabolic responses from rest to steady state determine contractile function in ischemic skeletal muscle. Am J Physiol 273:E233–E238
Timmons JA, Gustafsson T, Sundberg CJ, Jansson E, Greenhaff PL (1998) Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise. Am J Physiol 274:E377–E380
Timmons JA, Constantin-Teodosiu D, Poucher SM, Greenhaff PL (2004) Acetyl group availability influences phosphocreatine degradation even during intense muscle contraction. J Physiol 561:851–859. DOI 10.1113/jphysiol.2004.069419
Tschakovsky ME, Hughson RL (1999) Interaction of factors determining oxygen uptake at the onset of exercise. J Appl Physiol 86:1101–1113
Varnier M, Leese GP, Thompson J, Rennie MJ (1995) Stimulatory effect of glutamine on glycogen accumulation in human skeletal muscle. Am J Physiol 269:E309–E315
Vollestad NK, Tabata I, Medbo JI (1992) Glycogen breakdown in different human muscle fibre types during exhaustive exercise of short duration. Acta Physiol Scand 144:135–141
Wagenmakers AJ (1998) Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. Exerc Sport Sci Rev 26:287–314
Welch HG, Bonde-Petersen F, Graham T, Klausen K, Secher N (1977) Effects of hyperoxia on leg blood flow and metabolism during exercise. J Appl Physiol 42:385–390
Welch HG, Pedersen PK (1981) Measurement of metabolic rate in hyperoxia. J Appl Physiol 51:725–731
Whipp BJ, Wasserman K (1972) Oxygen uptake kinetics for various intensities of constant-load work. J Appl Physiol 33:351–356
Whipp BJ, Ward SA, Lamarra N, Davis JA, Wasserman K (1982) Parameters of ventilatory and gas exchange dynamics during exercise. J Appl Physiol 52:1506–1513
Whipp BJ (1987) Dynamics of pulmonary gas exchange. Circulation 76:VI18–VI28
Wilkerson DP, Campbell IT, Jones AM (2004) Influence of nitric oxide synthase inhibition on pulmonary O2 uptake kinetics during supra-maximal exercise in humans. J Physiol 561:623–635. DOI 10.1113/jphysiol.2004.071894
Wilkerson DP, Berger NJ, Jones AM (2005) Influence of hyperoxia on pulmonary O(2) uptake kinetics following the onset of exercise in humans. Respir Physiol Neurobiol (in press). DOI org/10.1016/j.resp.2005.09.006
Wilson DF, Erecinska M, Drown C, Silver IA (1979) The oxygen dependence of cellular energy metabolism. Arch Biochem Biophys 195:485–493
Wilson DF (1994) Factors affecting the rate and energetics of mitochondrial oxidative phosphorylation. Med Sci Sports Exerc 26:37–43
Wu G, Haynes TE, Li H, Yan W, Meininger CJ (2001) Glutamine metabolism to glucosamine is necessary for glutamine inhibition of endothelial nitric oxide synthesis. Biochem J 353:245–252
Yoshida T, Udo M, Ohmori T, Matsumoto Y, Uramoto T, Yamamoto K (1992) Day-to-day changes in oxygen uptake kinetics at the onset of exercise during strenuous endurance training. Eur J Appl Physiol Occup Physiol 64:78–83
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Marwood, S., Bowtell, J.L. Effects of glutamine and hyperoxia on pulmonary oxygen uptake and muscle deoxygenation kinetics. Eur J Appl Physiol 99, 149–161 (2007). https://doi.org/10.1007/s00421-006-0324-4
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DOI: https://doi.org/10.1007/s00421-006-0324-4