Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1994 Oct;94(4):1490–1495. doi: 10.1172/JCI117488

Relationship between the coenzyme A and the carnitine pools in human skeletal muscle at rest and after exhaustive exercise under normoxic and acutely hypoxic conditions.

R Friolet 1, H Hoppeler 1, S Krähenbühl 1
PMCID: PMC295290  PMID: 7929825

Abstract

Skeletal muscle CoA and carnitine metabolism were investigated in six human volunteers at rest and after exhaustive exercise under normoxic and hypoxic conditions. In comparison to the values at rest, exhaustive exercise was associated with a three- to fourfold increase in the skeletal muscle lactate, and with a twofold increase in the acetyl-CoA content, both under normoxic and hypoxic conditions. Since exercise did not significantly affect the skeletal muscle CoA radical (CoASH), total acid-soluble, or total CoA contents, the increase in the acetyl-CoA content was at the expense of short-chain acyl-CoAs different from acetyl-CoA. With exhaustive exercise, the skeletal muscle acetylcarnitine and short-chain acylcarnitine contents increased by a factor of three to four both under normoxic and hypoxic conditions. In contrast to the CoA pool, these increases were associated with a decrease in the free carnitine content, whereas the total acid-soluble and total carnitine contents were not affected by exercise. After exhaustive exercise, the skeletal muscle acetyl-CoA/CoASH ratio showed a linear correlation with the corresponding acetylcarnitine/free carnitine ratio. The plasma short-chain acylcarnitine concentration increased by a factor of two to three during exercise, and was not significantly different from the values at rest 40 min after completion of exercise. Thus, the current studies illustrate the close interaction between the CoA and carnitine pools in the exercising human skeletal muscle, and they underscore the important role of carnitine in maintaining the muscular CoASH content during exhaustive exercise.

Full text

PDF
1490

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bergstrom J. Percutaneous needle biopsy of skeletal muscle in physiological and clinical research. Scand J Clin Lab Invest. 1975 Nov;35(7):609–616. [PubMed] [Google Scholar]
  2. Bieber L. L., Emaus R., Valkner K., Farrell S. Possible functions of short-chain and medium-chain carnitine acyltransferases. Fed Proc. 1982 Oct;41(12):2858–2862. [PubMed] [Google Scholar]
  3. Brass E. P., Hoppel C. L. Carnitine metabolism in the fasting rat. J Biol Chem. 1978 Apr 25;253(8):2688–2693. [PubMed] [Google Scholar]
  4. Brass E. P., Hoppel C. L. Relationship between acid-soluble carnitine and coenzyme A pools in vivo. Biochem J. 1980 Sep 15;190(3):495–504. doi: 10.1042/bj1900495. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bremer J. Carnitine--metabolism and functions. Physiol Rev. 1983 Oct;63(4):1420–1480. doi: 10.1152/physrev.1983.63.4.1420. [DOI] [PubMed] [Google Scholar]
  6. Bremer J. Pyruvate dehydrogenase, substrate specificity and product inhibition. Eur J Biochem. 1969 Apr;8(4):535–540. doi: 10.1111/j.1432-1033.1969.tb00559.x. [DOI] [PubMed] [Google Scholar]
  7. Carlin J. I., Harris R. C., Cederblad G., Constantin-Teodosiu D., Snow D. H., Hultman E. Association between muscle acetyl-CoA and acetylcarnitine levels in the exercising horse. J Appl Physiol (1985) 1990 Jul;69(1):42–45. doi: 10.1152/jappl.1990.69.1.42. [DOI] [PubMed] [Google Scholar]
  8. Carroll J. E., Brooke M. H., Villadiego A., Norris B. J., Trefz J. I. 'Dystrophic' lipid myopathy in two sisters. Arch Neurol. 1986 Feb;43(2):128–131. doi: 10.1001/archneur.1986.00520020022010. [DOI] [PubMed] [Google Scholar]
  9. Carter A. L., Lennon D. L., Stratman F. W. Increased acetyl carnitine in rat skeletal muscle as a result of high-intensity short-duration exercise. Implications in the control of pyruvate dehydrogenase activity. FEBS Lett. 1981 Apr 6;126(1):21–24. doi: 10.1016/0014-5793(81)81023-x. [DOI] [PubMed] [Google Scholar]
  10. Cederblad G., Carlin J. I., Constantin-Teodosiu D., Harper P., Hultman E. Radioisotopic assays of CoASH and carnitine and their acetylated forms in human skeletal muscle. Anal Biochem. 1990 Mar;185(2):274–278. doi: 10.1016/0003-2697(90)90292-h. [DOI] [PubMed] [Google Scholar]
  11. Cederblad G., Lindstedt S. A method for the determination of carnitine in the picomole range. Clin Chim Acta. 1972 Mar;37:235–243. doi: 10.1016/0009-8981(72)90438-x. [DOI] [PubMed] [Google Scholar]
  12. Cooper D. M., Wasserman D. H., Vranic M., Wasserman K. Glucose turnover in response to exercise during high- and low-FIO2 breathing in man. Am J Physiol. 1986 Aug;251(2 Pt 1):E209–E214. doi: 10.1152/ajpendo.1986.251.2.E209. [DOI] [PubMed] [Google Scholar]
  13. Decombaz J., Gmuender B., Sierro G., Cerretelli P. Muscle carnitine after strenuous endurance exercise. J Appl Physiol (1985) 1992 Feb;72(2):423–427. doi: 10.1152/jappl.1992.72.2.423. [DOI] [PubMed] [Google Scholar]
  14. FRITZ I. B., SCHULTZ S. K., SRERE P. A. Properties of partially purified carnitine acetyltransferase. J Biol Chem. 1963 Jul;238:2509–2517. [PubMed] [Google Scholar]
  15. Ferretti G., Kayser B., Schena F., Turner D. L., Hoppeler H. Regulation of perfusive O2 transport during exercise in humans: effects of changes in haemoglobin concentration. J Physiol. 1992 Sep;455:679–688. doi: 10.1113/jphysiol.1992.sp019322. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Foster C. V., Harris R. C. Formation of acetylcarnitine in muscle of horse during high intensity exercise. Eur J Appl Physiol Occup Physiol. 1987;56(6):639–642. doi: 10.1007/BF00424803. [DOI] [PubMed] [Google Scholar]
  17. Harris R. C., Foster C. V. Changes in muscle free carnitine and acetylcarnitine with increasing work intensity in the Thoroughbred horse. Eur J Appl Physiol Occup Physiol. 1990;60(2):81–85. doi: 10.1007/BF00846025. [DOI] [PubMed] [Google Scholar]
  18. Harris R. C., Foster C. V., Hultman E. Acetylcarnitine formation during intense muscular contraction in humans. J Appl Physiol (1985) 1987 Jul;63(1):440–442. doi: 10.1152/jappl.1987.63.1.440. [DOI] [PubMed] [Google Scholar]
  19. Hiatt W. R., Regensteiner J. G., Wolfel E. E., Ruff L., Brass E. P. Carnitine and acylcarnitine metabolism during exercise in humans. Dependence on skeletal muscle metabolic state. J Clin Invest. 1989 Oct;84(4):1167–1173. doi: 10.1172/JCI114281. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ibañez J., Rama R., Riera M., Prats M. T., Palacios L. Severe hypoxia decreases oxygen uptake relative to intensity during submaximal graded exercise. Eur J Appl Physiol Occup Physiol. 1993;67(1):7–13. doi: 10.1007/BF00377696. [DOI] [PubMed] [Google Scholar]
  21. Idell-Wenger J. A., Grotyohann L. W., Neely J. R. Coenzyme A and carnitine distribution in normal and ischemic hearts. J Biol Chem. 1978 Jun 25;253(12):4310–4318. [PubMed] [Google Scholar]
  22. Jones N. L., Robertson D. G., Kane J. W., Hart R. A. Effect of hypoxia on free fatty acid metabolism during exercise. J Appl Physiol. 1972 Dec;33(6):733–738. doi: 10.1152/jappl.1972.33.6.733. [DOI] [PubMed] [Google Scholar]
  23. Krahenbuhl S., Brass E. P. Inhibition of hepatic propionyl-CoA synthetase activity by organic acids. Reversal of propionate inhibition of pyruvate metabolism. 1991 Mar 15-Apr 1Biochem Pharmacol. 41(6-7):1015–1023. doi: 10.1016/0006-2952(91)90209-n. [DOI] [PubMed] [Google Scholar]
  24. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  25. Lennon D. L., Stratman F. W., Shrago E., Nagle F. J., Madden M., Hanson P., Carter A. L. Effects of acute moderate-intensity exercise on carnitine metabolism in men and women. J Appl Physiol Respir Environ Exerc Physiol. 1983 Aug;55(2):489–495. doi: 10.1152/jappl.1983.55.2.489. [DOI] [PubMed] [Google Scholar]
  26. Linnarsson D., Karlsson J., Fagraeus L., Saltin B. Muscle metabolites and oxygen deficit with exercise in hypoxia and hyperoxia. J Appl Physiol. 1974 Apr;36(4):399–402. doi: 10.1152/jappl.1974.36.4.399. [DOI] [PubMed] [Google Scholar]
  27. Lysiak W., Lilly K., DiLisa F., Toth P. P., Bieber L. L. Quantitation of the effect of L-carnitine on the levels of acid-soluble short-chain acyl-CoA and CoASH in rat heart and liver mitochondria. J Biol Chem. 1988 Jan 25;263(3):1151–1156. [PubMed] [Google Scholar]
  28. Pande S. V., Caramancion M. N. A simple radioisotopic assay of acetylcarnitine and acetyl-CoA at picomolar levels. Anal Biochem. 1981 Mar 15;112(1):30–38. doi: 10.1016/0003-2697(81)90256-6. [DOI] [PubMed] [Google Scholar]
  29. Pearson D. J., Tubbs P. K. Carnitine and derivatives in rat tissues. Biochem J. 1967 Dec;105(3):953–963. doi: 10.1042/bj1050953. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Ramsay R. R., Arduini A. The carnitine acyltransferases and their role in modulating acyl-CoA pools. Arch Biochem Biophys. 1993 May;302(2):307–314. doi: 10.1006/abbi.1993.1216. [DOI] [PubMed] [Google Scholar]
  31. Sahlin K. Muscle carnitine metabolism during incremental dynamic exercise in humans. Acta Physiol Scand. 1990 Mar;138(3):259–262. doi: 10.1111/j.1748-1716.1990.tb08845.x. [DOI] [PubMed] [Google Scholar]
  32. Solberg H. E., Bremer J. Formation of branched chain acylcarnitines in mitochondria. Biochim Biophys Acta. 1970 Nov 24;222(2):372–380. doi: 10.1016/0304-4165(70)90126-1. [DOI] [PubMed] [Google Scholar]
  33. Spriet L. L., Dyck D. J., Cederblad G., Hultman E. Effects of fat availability on acetyl-CoA and acetylcarnitine metabolism in rat skeletal muscle. Am J Physiol. 1992 Sep;263(3 Pt 1):C653–C659. doi: 10.1152/ajpcell.1992.263.3.C653. [DOI] [PubMed] [Google Scholar]
  34. Spurway N. C. Aerobic exercise, anaerobic exercise and the lactate threshold. Br Med Bull. 1992 Jul;48(3):569–591. doi: 10.1093/oxfordjournals.bmb.a072564. [DOI] [PubMed] [Google Scholar]
  35. Uziel G., Garavaglia B., Di Donato S. Carnitine stimulation of pyruvate dehydrogenase complex (PDHC) in isolated human skeletal muscle mitochondria. Muscle Nerve. 1988 Jul;11(7):720–724. doi: 10.1002/mus.880110708. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES