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1 Integrative Biology/University of California, University of California, Berkeley, CA, USA
2 Cardiology, University of Colorado, Denver, CO, USA
3 Endocrinology, Diabetes, and Metabolism, University of Colorado, Denver, C), USA
* To whom correspondence should be addressed. E-mail: gbrooks{at}socrates.berkeley.edu.
We describe the isotopic exchange of lactate and pyruvate following arm vein infusion of [3-13C]lactate in men during rest and exercise. We tested the hypothesis that working muscle (limb net lactate and pyruvate exchange) is the source of the elevated systemic lactate-to-pyruvate ratio (L/P) during exercise. We also hypothesized that the isotopic equilibration between lactate and pyruvate would decrease in arterial blood as glycolytic flux, as determined by relative exercise intensity, increased. Nine men were studied at rest and during exercise before and after 9 weeks of endurance training. Although during exercise arterial [pyruvate] decreased to below rest values (P < 0.05), pyruvate net release from working muscle was as large as lactate net release under all exercise conditions. Exogenous (arterial) lactate was the predominant origin of pyruvate released from working muscle. With no significant effect of exercise intensity or training, arterial isotopic equilibration [(IEpyruvate/IElactate) .(100%)] decreased significantly (P < 0.05) from 60 ± 3.1% at rest to an average value of 12 ± 2.7% during exercise, and there were no changes in femoral venous isotopic equilibration. These data show that: (1) the isotopic equilibration between lactate and pyruvate in arterial blood decreases significantly during exercise, (2) working muscle is not solely responsible for the decreased arterial isotopic equilibration or elevated arterial L/P occurring during exercise, (3) working muscle releases similar amounts of lactate and pyruvate, the predominant source of the latter being arterial lactate, (4) pyruvate clearance from blood occurs extensively outside of working muscle and (5) working muscle also releases alanine, but alanine release is an order of magnitude smaller than lactate or pyruvate release. These results portray the complexity of metabolic integration among diverse tissue beds in vivo.
This article has been cited by other articles:
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  T. Stellingwerff, G. J. F. Heigenhauser, and L. L. Spriet Reply to letter "Pyruvate metabolism in working human skeletal muscle" by Henderson et al. Am J Physiol Endocrinol Metab, April 1, 2007; 292(4): E1238 - E1239. [Full Text] [PDF]
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G. C. Henderson, M. A. Horning, G. A. Wallis, and G. A. Brooks Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E366 - E366. [Full Text] [PDF]
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 M. I. Lindinger, G. A. Brooks, G. C. Henderson, T. Hashimoto, T. Mau, J. A. Fattor, M. A. Horning, R. Hussien, H.-S. Cho, N. Faghihnia, et al. Lactic acid accumulation is an advantage/disadvantage during muscle activity J Appl Physiol, June 1, 2006; 100(6): 2100 - 2102. [Full Text] [PDF]
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T. Stellingwerff, P. J. LeBlanc, M. G. Hollidge, G. J. F. Heigenhauser, and L. L. Spriet Hyperoxia decreases muscle glycogenolysis, lactate production, and lactate efflux during steady-state exercise Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1180 - E1190. [Abstract] [Full Text] [PDF]
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T. Hashimoto, R. Hussien, and G. A. Brooks Colocalization of MCT1, CD147, and LDH in mitochondrial inner membrane of L6 muscle cells: evidence of a mitochondrial lactate oxidation complex Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1237 - E1244. [Abstract] [Full Text] [PDF]
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