Effect of endurance training on muscle tca cycle metabolism during exercise in humans
Abstract
We tested the theory that links the capacity to perform prolonged exercise with the size of the muscle tricarboxylic acid (TCA) cycle intermediate (TCAI) pool. We hypothesized that endurance training would attenuate the exercise-induced increase in TCAI concentration ([TCAI]); however, the lower [TCAI] would not compromise cycle endurance capacity. Eight men (22 +/- 1 yr) cycled at approximately 80% of initial peak oxygen uptake before and after 7 wk of training (1 h/day, 5 days/wk). Biopsies (vastus lateralis) were obtained during both trials at rest, after 5 min, and at the point of exhaustion during the pretraining trial (42 +/- 6 min). A biopsy was also obtained at the end of exercise during the posttraining trial (91 +/- 6 min). In addition to improved performance, training increased (P < 0.05) peak oxygen uptake and citrate synthase maximal activity. The sum of four measured TCAI was similar between trials at rest but lower after 5 min of exercise posttraining [2.7 +/- 0.2 vs. 4.3 +/- 0.2 mmol/kg dry wt (P < 0.05)]. There was a clear dissociation between [TCAI] and endurance capacity because the [TCAI] at the point of exhaustion during the pretraining trial was not different between trials (posttraining: 2.9 +/- 0.2 vs. pretraining: 3.5 +/- 0.2 mmol/kg dry wt), and yet cycle endurance time more than doubled in the posttraining trial. Training also attenuated the exercise-induced decrease in glutamate concentration (posttraining: 4.5 +/- 0.7 vs. pretraining: 7.7 +/- 0.6 mmol/kg dry wt) and increase in alanine concentration (posttraining: 3.3 +/- 0.2 vs. pretraining: 5.6 +/- 0.3 mmol/kg dry wt; P < 0.05), which is consistent with reduced carbon flux through alanine aminotransferase. We conclude that, after aerobic training, cycle endurance capacity is not limited by a decrease in muscle [TCAI].
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In humans, a dissociation between TCA cycle pool size and aerobic phosphorylation was demonstrated, suggesting that TCA intermediate content does not represent any functional importance to oxidative phosphorylation.
“In humans, a dissociation between TCA cycle pool size and aerobic phosphorylation was demonstrated [184,185], suggesting that TCA intermediate content does not represent any functional importance to oxidative phosphorylation [182].”
From Regulation of Energy Substrate Metabolism in Endurance Exercise (2021) · cites this paper as [185]
Cites
(1975) · Journal of AOAC INTERNATIONAL · doi:10.1093/jaoac/58.5.1085 · Cited by 20,078 · see citing works
Adaptations of skeletal muscle to endurance exercise and their metabolic consequences
Holloszy, J. O., & Coyle, E. F. (1984) · Journal of Applied Physiology · doi:10.1152/jappl.1984.56.4.831 · Cited by 1,985 · see citing works
Percutaneous Needle Biopsy of Skeletal Muscle in Physiological and Clinical Research
Bergström, J. P. (1975) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517509095787 · Cited by 1,159 · see citing works
Harris, R. C., Hultman, E., & Nordesjö, L. ‐. (1974) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.3109/00365517409082477 · Cited by 857 · see citing works
Enzymatic analysis; a practical guide
(1993) · General Pharmacology The Vascular System · doi:10.1016/0306-3623(93)90404-l · Cited by 522 · see citing works
Passonneau, J. V., & Lowry, O. H. (1993) · Humana Press eBooks · doi:10.1007/978-1-60327-407-4 · Cited by 300 · see citing works
Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise
Sahlin, K., Katz, A., & Broberg, S. (1990) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1990.259.5.c834 · Cited by 274 · see citing works
Chronic stimulation of mammalian muscle: changes in enzymes of six metabolic pathways
Henriksson, J., Chi, M. M., Hintz, C. S., Young, D. A., Kaiser, K. K., Salmons, S., & Lowry, O. H. (1986) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1986.251.4.c614 · Cited by 253 · see citing works
Changes in skeletal muscle in males and females following endurance training
Carter, S., Rennie, C. D., Hamilton, S. J., & Tarnopolsky, M. A. (2001) · Canadian Journal of Physiology and Pharmacology · doi:10.1139/y01-008 · Cited by 234 · see citing works
Regulation of the citric acid cycle in mammalian systems
WILLIAMSON, J. R., & Cooper, R. H. (1980) · FEBS Letters · doi:10.1016/0014-5793(80)80572-2 · Cited by 180 · see citing works
Radioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle
Cederblad, G., Carlin, J. I., Constantin‐Teodosiu, D., Harper, P., & Hultman, E. (1990) · Analytical Biochemistry · doi:10.1016/0003-2697(90)90292-h · Cited by 173 · see citing works
Effect of Exercise on Amino Acid Concentrations in Skeletal Muscle and Plasma
Henriksson, J. (1991) · Journal of Experimental Biology · doi:10.1242/jeb.160.1.149 · Cited by 142 · see citing works
(2000) · Wiley eBooks · doi:10.1002/9780470693766 · Cited by 100 · see citing works
Carbohydrate supplementation attenuates IMP accumulation in human muscle during prolonged exercise
SPENCER, M. K., Yan, Z., & Katz, A. (1991) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1991.261.1.c71 · Cited by 98 · see citing works
Biochemical and histochemical adaptation to sprint training in young athletes
Cadefau, J. A., Casademont, J., Grau, J. M., FERNÁNDEZ, J., BALAGUER, A., VERNET, M., Cussó, R., & Urbano-Márquez, A. (1990) · Acta Physiologica Scandinavica · doi:10.1111/j.1748-1716.1990.tb09008.x · Cited by 93 · see citing works
Training and muscle ammonia and amino acid metabolism in humans during prolonged exercise
Graham, T. E., Turcotte, L. P., Kiens, B., & Richter, E. A. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.78.2.725 · Cited by 91 · see citing works
Tricarboxylic acid cycle intermediates in human muscle at rest and during prolonged cycling
Gibala, M. J., Tarnopolsky, M. A., & Graham, T. E. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.272.2.e239 · Cited by 84 · see citing works
Effect of low glycogen on carbohydrate and energy metabolism in human muscle during exercise
SPENCER, M. K., Yan, Z., & Katz, A. L. (1992) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.1992.262.4.c975 · Cited by 84 · see citing works
van Hall, G., Saltin, B., & Wagenmakers, A. J. M. (1999) · Clinical Science · doi:10.1042/cs19980422 · Cited by 67 · see citing works
Bruce, M., Constantin‐Teodosiu, D., Greenhaff, P. L., Boobis, L., Williams, C., & Bowtell, J. L. (2001) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.2001.280.4.e669 · Cited by 53 · see citing works
Sahlin, K., Jorfeldt, L., Henriksson, K. G., Lewis, S. F., & Haller, R. G. (1995) · Clinical Science · doi:10.1042/cs0880687 · Cited by 52 · see citing works
Ji, L. L., Miller, R. H., NAGLE, F. J., Lardy, H. A., & Stratman, F. W. (1987) · Metabolism · doi:10.1016/0026-0495(87)90111-9 · Cited by 45 · see citing works
Effect of summer intermission on skeletal muscle of adolescent soccer players.
Amigó, N., Cadefau, J. A., Ferrer, I., Tarrados, N., & Cussó, R. (1998) · PubMed · Cited by 41 · see citing works
Gibala, M. J., Peirce, N., Constantin‐Teodosiu, D., & Greenhaff, P. L. (2002) · The Journal of Physiology · doi:10.1113/jphysiol.2001.012983 · Cited by 37 · see citing works
van Hall, G., Saltin, B., & Wagenmakers, A. J. M. (1999) · Clinical Science · doi:10.1042/cs0970557 · Cited by 37 · see citing works
Free amino acids in muscle: effect of muscle fiber population and denervation
Turinsky, J., & Long, C. L. (1990) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1990.258.3.e485 · Cited by 34 · see citing works
Hargreaves, M., & Thompson, M. W. (1999) · Human Kinetics eBooks · Cited by 31 · see citing works
Essén-Gustavsson, B., & Blomstrand, E. (2002) · Acta Physiologica Scandinavica · doi:10.1046/j.1365-201x.2002.00942.x · Cited by 28 · see citing works
Short-term training attenuates muscle TCA cycle expansion during exercise in women
Dawson, K. D., Howarth, K. R., Tarnopolsky, M. A., Wong, N. D., & Gibala, M. J. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01118.2002 · Cited by 19 · see citing works
Alanine metabolism in skeletal muscle in tissue culture
Pardridge, W. M., & Davidson, M. B. (1979) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(79)90322-2 · Cited by 11 · see citing works
Amino Acid Metabolism in Exercise
Wagenmakers, A. J. M. (2000) · Wiley eBooks · doi:10.1002/9780470693766.ch9 · Cited by 8 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Goncalves, R. L. S., Quinlan, C. L., Perevoshchikova, I. V., Hey-Mogensen, M., & Brand, M. D. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.619072 · Cited by 329 · see citing works
Training-Induced Changes in Mitochondrial Content and Respiratory Function in Human Skeletal Muscle
Granata, C., Jamnick, N. A., & Bishop, D. J. (2018) · Sports Medicine · doi:10.1007/s40279-018-0936-y · Cited by 247 · see citing works
Application of Metabolomics to Cardiovascular Biomarker and Pathway Discovery
Lewis, G. D., Asnani, A. H., & Gerszten, R. E. (2008) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.03.043 · Cited by 229 · see citing works
Al‐Khelaifi, F., Diboun, I., Donati, F., Botrè, F., Alsayrafi, M., Georgakopoulos, C. G., Suhre, K., Yousri, N. A., & Elrayess, M. A. (2018) · Sports Medicine - Open · doi:10.1186/s40798-017-0114-z · Cited by 139 · see citing works
Regulation of Energy Substrate Metabolism in Endurance Exercise
Alghannam, A. F., Ghaith, M. M., & Alhussain, M. H. (2021) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph18094963 · Cited by 104 · see citing works
Sillen, M. J. H., Franssen, F. M. E., Gosker, H. R., Wouters, E. F. �., & Spruit, M. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0069391 · Cited by 104 · see citing works
Rapid metabolic evolution in human prefrontal cortex
Fu, X., Giavalisco, P., Liu, X., Catchpole, G., Fu, N., Ning, Z., Guo, S., Zheng, Y., Somel, M., Pääbo, S., et al. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1019164108 · Cited by 99 · see citing works
Vigelsø, A., Andersen, N. B., & Dela, F. (2014) · Europe PMC (PubMed Central) · Cited by 96 · see citing works
Molecular insights of exercise therapy in disease prevention and treatment
Walzik, D., Chirino, T. Y. W., Zimmer, P., & Joisten, N. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01841-0 · Cited by 89 · see citing works
Krebs cycle: activators, inhibitors and their roles in the modulation of carcinogenesis
Gasmi, A., Peana, M., Arshad, M., Butnariu, M., Menzel, A., & Bjørklund, G. (2021) · Archives of Toxicology · doi:10.1007/s00204-021-02974-9 · Cited by 82 · see citing works
Bowtell, J. L., Marwood, S., Bruce, M., Constantin-Teodosiu, D., & Greenhaff, P. L. (2007) · Sports Medicine · doi:10.2165/00007256-200737120-00005 · Cited by 81 · see citing works
Gram, M., Vigelsø, A., Yokota, T., HANSEN, C. N., Helge, J. W., Hey‐Mogensen, M., & Dela, F. (2014) · Experimental Gerontology · doi:10.1016/j.exger.2014.08.013 · Cited by 77 · see citing works
Mitochondrial energetic metabolism: A simplified model of TCA cycle with ATP production
Nazaret, C., Heiske, M., Thurley, K., & Mazat, J. (2008) · Journal of Theoretical Biology · doi:10.1016/j.jtbi.2008.09.037 · Cited by 74 · see citing works
Li, Y., Dash, R. K., Kim, J., Saidel, G. M., & Cabrera, M. E. (2008) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00094.2008 · Cited by 46 · see citing works
López-Bote, C. J., Toldrá, F., Daza, A., Ferrer, J. M., Menoyo, D., Silio, L. F., & Rodríguez, M. C. (2007) · Meat Science · doi:10.1016/j.meatsci.2007.08.002 · Cited by 39 · see citing works
Dash, R. K., Li, Y., Kim, J., Saidel, G. M., & Cabrera, M. E. (2008) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2007.913422 · Cited by 34 · see citing works
Metabolic profiling of elite athletes with different cardiovascular demand
Al‐Khelaifi, F., Donati, F., Botrè, F., Latiff, A. A., Abraham, D., Hingorani, A. D., Georgakopoulos, C. G., Suhre, K., Yousri, N. A., & Elrayess, M. A. (2019) · Scandinavian Journal of Medicine and Science in Sports · doi:10.1111/sms.13425 · Cited by 30 · see citing works
Abdullah, M., Kornegay, J. N., Honcoop, A. C., Parry, T. L., Balog-Alvarez, C. J., O’Neal, S., Bain, J. R., Muehlbauer, M. J., Newgard, C. B., Patterson, C., et al. (2017) · Metabolites · doi:10.3390/metabo7030038 · Cited by 30 · see citing works
Effects of exercise‐induced beta‐hydroxybutyrate on muscle function and cognitive function
Kwak, S. E., Bae, J. H., Lee, J. H., Shin, H. E., Zhang, D., Cho, S. C., & Song, W. J. (2021) · Physiological Reports · doi:10.14814/phy2.14497 · Cited by 28 · see citing works
Dash, R. K., Li, Y., Kim, J., Beard, D. A., Saidel, G. M., & Cabrera, M. E. (2008) · PLoS ONE · doi:10.1371/journal.pone.0003168 · Cited by 26 · see citing works
Dawson, K. D., Baker, D. J., Greenhaff, P. L., & Gibala, M. J. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2004.079939 · Cited by 21 · see citing works
Mourtzakis, M., Graham, T. E., González‐Alonso, J., & Saltin, B. (2008) · Journal of Applied Physiology · doi:10.1152/japplphysiol.90394.2008 · Cited by 18 · see citing works
Effects of a Supplementation during Exercise and Recovery
Thomas, C., Perrey, S., Saad, H. B., Delage, M., Dupuy, A., Cristol, J., & Mercier, J. G. (2007) · International Journal of Sports Medicine · doi:10.1055/s-2007-965021 · Cited by 17 · see citing works
Bangsbo, J., Gibala, M. J., Howarth, K. R., & Krustrup, P. (2006) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-006-0075-4 · Cited by 15 · see citing works
Metabolomic profiles of being physically active and less sedentary: a critical review
Tian, Q., Corkum, A. E., Moaddel, R., & Ferrucci, L. (2021) · Metabolomics · doi:10.1007/s11306-021-01818-y · Cited by 15 · see citing works
Effects of glutamine and hyperoxia on pulmonary oxygen uptake and muscle deoxygenation kinetics
Marwood, S., & Bowtell, J. L. (2006) · European Journal of Applied Physiology · doi:10.1007/s00421-006-0324-4 · Cited by 13 · see citing works
Wang, F., Han, J., He, Q., Geng, Z., Deng, Z., & Qiao, D. (2015) · Journal of Analytical Methods in Chemistry · doi:10.1155/2015/315217 · Cited by 12 · see citing works
Molecular Profiling of Athletes Performing High-Intensity Exercises in Extreme Environments
Malsagova, K. A., Kopylov, A. T., Stepanov, A. A., Enikeev, D. V., Potoldykova, N. V., Balakin, E. I., Pustovoyt, V. I., & Kaysheva, A. L. (2023) · Sports · doi:10.3390/sports11020036 · Cited by 10 · see citing works
Proteomics and metabolomics research in exercise and sport
Al‐Khelaifi, F., Abraham, D., Diboun, I., & Elrayess, M. A. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-816193-7.00023-3 · Cited by 9 · see citing works
Marwood, S., & Bowtell, J. L. (2008) · Journal of Sports Sciences · doi:10.1080/02640410801930200 · Cited by 9 · see citing works
Belfry, G. R., Noble, E. G., & Taylor, A. W. (2015) · The Journal of Strength and Conditioning Research · doi:10.1519/jsc.0000000000000842 · Cited by 9 · see citing works
Murray, K. O., Maurer, G. S., Gioscia‐Ryan, R. A., Zigler, M. C., Ludwig, K. R., D’Alessandro, A., Reisz, J. A., Rossman, M. J., Seals, D. R., & Clayton, Z. S. (2024) · GeroScience · doi:10.1007/s11357-024-01062-x · Cited by 8 · see citing works
Effect of triheptanoin on muscle metabolism during submaximal exercise in horses
McCue, M. E., Valberg, S. J., Pagan, J. D., Essén-Gustavsson, B., & Roe, C. R. (2009) · American Journal of Veterinary Research · doi:10.2460/ajvr.70.8.1043 · Cited by 7 · see citing works
Stob, N. R., Seals, D. R., Jensen, J., van Baak, M. A., Steig, A. J., Lindstrom, R. C., Bikman, B. T., & Bell, C. (2007) · Experimental Physiology · doi:10.1113/expphysiol.2007.038174 · Cited by 7 · see citing works
Ragland, T. J., & Malin, S. K. (2024) · Physiological Reports · doi:10.14814/phy2.15987 · Cited by 6 · see citing works
Takahashi, K., Mukai, K., Takahashi, Y., Ebisuda, Y., Hatta, H., & Kitaoka, Y. (2024) · Journal of Experimental Biology · doi:10.1242/jeb.246896 · Cited by 6 · see citing works
Systemic metabolite kinetics mirror skeletal muscle energy metabolism during acute aerobic exercise
Walzik, D., Wenzel, C., Strotkötter, J. E., Hoenen, L., Chirino, T. Y. W., Trebing, S., McCann, A., Ueland, P. M., Zimmer, P., & Joisten, N. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00715.2025 · Cited by 3 · see citing works
Cuproptosis and physical training: A review
Kordi, N., Saydi, A., Azimi, M., Mazdarani, F. H., Gadruni, K., Jung, F., & Karami, S. (2024) · Clinical Hemorheology and Microcirculation · doi:10.3233/ch-242329 · Cited by 4 · see citing works
Kimoloi, S. (2023) · International Journal of Sport Exercise and Health Research · doi:10.31254/sportmed.7208 · Cited by 1 · see citing works
Silveira, L. R., Hirabara, S. M., Lambertucci, R. H., Leandro, C. V. G., Fiamoncini, J., Pinheiro, C. H. D. J., D'Angelo, A. C. A., Bassit, R. A., Pithon‐Curi, T. C., & Curi, R. (2008) · Revista Brasileira de Medicina do Esporte · doi:10.1590/s1517-86922008000100011 · Cited by 7 · see citing works
The Effects of Exercise on LINE-1 Regulation
Romero, M. A. (2019)
Metabolomics – Nutritional and Physiological Challenges
Suárez, M., Canela-Canela, N., Bas-Prior, J. M. D., Puiggròs, F., Arola, L., & Caimari, A. (2020) · Elsevier eBooks · doi:10.1016/b978-0-08-100596-5.22826-6
Yashin, T. A., Grishina, Z. V., Парастаев, С. А., & Zholinsky, A. V. (2025) · Extreme Medicine · doi:10.47183/mes.2025-288 · Cited by 1 · see citing works
Si, J., Tian, H., Guo, M., Lin, Y., Gong, Y., Wang, Y., & Peng, L. (2026) · Molecular Biology Reports · doi:10.1007/s11033-026-12237-4
Grishina, Z. V., Владимировна, Л. Е., Yashin, T. A., Сергеевич, Г. Н., Парастаев, С. А., Анатольевич, Д. А., Козлов, К. В., Деханов, П. А., Zavialov, V. V., & Вячеславович, К. А. (2026) · Медицина: теория и практика · doi:10.56871/mtp.2026.57.89.007
Urinary Metabolic Profiles Before and After the Winter Training Season in Female Soccer Players
Kim, H. Y., Lee, J. D., Lee, H.-S., Chang, J., Kim, S., Hwang, G., & Kim, K. (2026) · Metabolites · doi:10.3390/metabo16090675
- Authors
- Howarth, K. R., LeBlanc, P. J., Heigenhauser, G. J. F., & Gibala, M. J.
- Affiliations
- McMaster University (CA)
- Venue
- Journal of Applied Physiology
- Publisher
- American Physiological Society
- Published
- 2004-08
- Volume
- 97
- Issue
- 2
- Pages
- 579-584
- ISSN
- 0161-7567 (ISSN-L)
- 8750-7587
- 1522-1601
- OpenAlex
- W2098276006
- Cited by
- 50
- References
- 30
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 5 · 2023: 2 · 2021: 4 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 1 · 2015: 2 · 2014: 4 · 2013: 1
- FWCI
- 6.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Applied Physiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
- Keywords
- endurance training, TCA cycle, TCA cycle intermediates, muscle metabolism, citrate synthase, glutamate, alanine, alanine aminotransferase, vastus lateralis, aerobic exercise, peak oxygen uptake
- MeSH terms
- Adult, Alanine Transaminase, Amino Acids, Blood Glucose, Citrate (si)-Synthase, Citric Acid Cycle, Glycogen, Heart Rate, Humans, Male, Oxygen Consumption, Physical Endurance, Exercise, Respiratory Mechanics, Muscle, Skeletal, Lactic Acid
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review