PDH activation by dichloroacetate reduces TCA cycle intermediates at rest but not during exercise in humans

American Journal of Physiology - Endocrinology and Metabolism

Volumn 277, Issue 1 40-1, 1999, Pages

  Gibala, Martin J ^a,b   Saltin, Bengt ^a  

^a Rigshospitalet   (Denmark)

^b MCMASTER UNIVERSITY   (Canada)

Author keywords

Anaplerosis; Knee extensor exercise; Pyruvate dehydrogenase complex; Skeletal muscle; Tricarboxylic acid cycle intermediates

Indexed keywords

DICHLOROACETIC ACID; PYRUVATE DEHYDROGENASE;

ADULT; AEROBIC METABOLISM; ARTICLE; CITRIC ACID CYCLE; ENZYME ACTIVATION; ENZYME ACTIVITY; FEMALE; GLYCOLYSIS; HUMAN; HUMAN EXPERIMENT; LEG MOVEMENT; MALE; MUSCLE EXERCISE; MUSCLE METABOLISM; NORMAL HUMAN; OXYGEN CONSUMPTION; PRIORITY JOURNAL;

EID: 0032806174     PISSN: 01931849     EISSN: None     Source Type: Journal    
DOI: 10.1152/ajpendo.1999.277.1.e33     Document Type: Article

References (30)

1. Andersen, P., and B. Saltin. Maximal perfusion of skeletal muscle in man. J. Physiol. (Lond.) 366: 233-249, 1985.
2. Anderson, J. W., D. Karounous, and T. Yoneyama. Dichloroacetate-induced changes in liver of normal and diabetic rats. Proc. Soc. Exp. Biol. Med. 149: 814-821, 1975.
3. Aragón, J. J., and J. M. Lowenstein. The purine nucleotide cycle. Comparison of the levels of citric acid cycle intermediates with the operation of the purine nucleotide cycle in rat skeletal muscle during exercise and recovery from exercise. Eur. J. Biochem. 110: 371-377, 1980.
4. Bergmeyer, H. U. Methods of Enzymatic Analysis. New York: Academic, 1974.
5. Bergström, J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand. J. Clin. Lab. Invest. 35: 609-616, 1975.
6. Clark, A. S., W. E. Mitch, M. N. Goodman, J. M. Fagen, M. A. Goheer, and R. T. Curnow. Dichloroacetate inhibits glycolysis and augments insulin-stimulated glycogen synthesis in rat muscle. J. Clin. Invest. 79: 588-594, 1987.
7. Constantin-Teodosiu, D., G. Cederblad, and E. Hultman. A sensitive radioisotopic assay of pyruvate dehydrogenase complex in human muscle tissue. Anal. Biochem. 198: 347-351, 1991.
8. Constantin-Teodosiu, D., E. J. Simpson, and P. L. Greenhaff. Effects of pyruvate, dichloroacetate and adrenaline infusion on pyruvate dehydrogenase complex activation and tricarboxylic acid cycle intermediates in human skeletal muscle (Abstract). J. Physiol. (Lond.) 506: 102P, 1998.
9. Gibala, M. J., and P. Krustrup. The effect of dichloroacetate (DCA) on pyruvate dehydrogenase complex activation during intense exercise in human skeletal muscle (Abstract). Pflügers Arch. 435: R72, 1998.
10. Gibala, M. J., D. A. MacLean, T. E. Graham, and B. Saltin. Anaplerotic processes in human skeletal muscle during brief dynamic exercise. J. Physiol. (Lond.) 502: 703-713, 1997.
11. Gibala, M. J., D. A. MacLean, T. E. Graham, and B. Saltin. Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am. J. Physiol. 275 (Endocrinol. Metab. 38): E235-E242, 1998.
12. Gibala, M. J., M. A. Tarnopolsky, and T. E. Graham. Tricarboxylic acid cycle intermediates in human muscle at rest and during prolonged cycling. Am. J. Physiol. 272 (Endocrinol. Metab. 35): E239-E244, 1997.
13. Graham, T. E., and M. J. Gibala. Anaplerosis of the tricarboxylic acid cycle during exercise in human skeletal muscle: magnitude, sources and potential physiological significance. In: Skeletal Muscle Metabolism in Exercise and Diabetes, edited by E. A. Richter, H. Galbo, B. Kiens, and B. Saltin. New York: Plenum, 1998, p. 271-286.
14. Harris, R. C., E. Hultman, and L. O. Nordesjo. Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Scand. J. Clin. Lab. Invest. 33: 109-120, 1974.
15. Kornberg, H. L. Anaplerotic sequences and their role in metabolism. In: Essays in Biochemistry, edited by P. N Campbell and R. D. Marshall. London: Academic, 1966, p. 1-31.
16. Ludvik, B., G. Mayer, S. Stifter, D. Putz, U. Barnas, and H. Graf. Effects of dichloroacetate on exercise performance in healthy volunteers. Pflügers Arch. 423: 251-254, 1993.
17. Ludvik, B., G. Peer, A. Berzlanovich, S. Stifter, and H. Graf. Effects of dichloroacetate and bicarbonate on hemodynamic parameters in healthy volunteers. Clin. Sci. (Colch.) 80: 47-51, 1991.
18. Mariash, C. N., and J. H. Oppenheimer. Stimulation of malic enzyme formation in hepatocyte culture by metabolites: evidence favouring a nonglycolytic metabolite as the proximate induction signal. Metabolism 33: 545-552, 1983.
19. Passoneau, J. V., and O. H. Lowry. Enzymatic Analysis: A Practical Guide. Totowa, NJ: Humana, 1993.
20. Putman, C. L., L. L. Spriet, E. Hultman, M. I. Lindinger, L. C. Lands, R. S. McKelvie, G. Cederblad, N. L. Jones, and G. J. F. Heigenhauser. Pyruvate dehydrogenase activity and acetyl group accumulation during exercise after different diets. Am. J. Physiol. 265 (Endocrinol. Metab. 28): E752-E760, 1993
21. Richardson, R. S., and B. Saltin. Human muscle blood flow and metabolism studied in the isolated quadriceps muscles. Med. Sci. Sports Exerc. 30: 28-33, 1998.
22. Sahlin, K., A. Katz, and S. Broberg. Tricarboxylic acid cycle intermediates in human muscle during prolonged exercise. Am. J. Physiol. 259 (Cell Physiol. 28): C834-C841, 1990.
23. Snell, K. Muscle alanine synthesis and hepatic gluconeogenesis. Biochem. Soc. Trans. 8: 205-213, 1980.
24. Spencer, M. K., and A. Katz. Role of glycogen in control of glycolysis and IMP formation in human muscle during exercise. Am. J. Physiol. 260 (Endocrinol. Metab. 23): E859-E864, 1991.
25. Stacpoole, P. W. The pharmacology of dichloroacetate. Metabolism 38: 1124-1144, 1989.
26. Timmons, J. A., T. Gustafsson, C. J. Sundberg, E. Jansson, and P. L. Greenhaff. Muscle acetyl group availability is a major determinant of oxygen deficit in humans during submaximal exercise. Am. J. Physiol. 274 (Endocrinol. Metab. 37): E377-E380, 1998.
27. Timmons, J. A., T. Gustafsson, C. J. Sundberg, E. Jansson, E. Hultman, L. Kaijser, J. Chwalbinska-Moneta, D. Constantin-Teodosiu, I. Macdonald, and P. L. Greenhaff. Substrate availability limits human skeletal muscle oxidative ATP regeneration at the onset of ischemic exercise. J. Clin. Invest. 101: 79-85, 1998.
28. Timmons, J. A., S. M. Poucher, D. Constantin-Teodosiu, I. A. MacDonald, and P. L. Greenhaff. Metabolic responses from rest to steady state determine contractile function in ischemic skeletal muscle. Am. J. Physiol. 273 (Endocrinol. Metab. 36): E223-E238, 1997.
29. Wagenmakers, A. J. M. Muscle amino acid metabolism at rest and during exercise: role in human physiology and metabolism. In: Exercise and Sports Science Reviews, edited by J. O. Holloszy. Baltimore, MD: Williams and Wilkins, 1998, p. 287-314.
30. Weiland, O. H. The mammalian pyruvate dehydrogenase complex: structure and regulation. Rev. Physiol. Biochem. Pharmacol. 96: 124-170, 1983.