Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1971 Dec;50(12):2703–2714. doi: 10.1172/JCI106771

Amino acid metabolism in exercising man

Philip Felig 1,2, John Wahren 1,2
PMCID: PMC292220  PMID: 5129318

Abstract

Arterial concentration and net exchange across the leg and splanchnic bed of 19 amino acids were determined in healthy, postabsorptive subjects in the resting state and after 10 and 40 min of exercise on a bicycle ergometer at work intensities of 400, 800, and 1200 kg-m/min. Arterio-portal venous differences were measured in five subjects undergoing elective cholecystectomy.

In the resting state significant net release from the leg was noted for 13 amino acids, and significant splanchnic uptake was observed for 10 amino acids. Peripheral release and splanchnic uptake of alanine exceeded that of all other amino acids, accounting for 35-40% of total net amino acid exchange. Alanine and other amino acids were released in small amounts (relative to net splanchnic uptake) by the extrahepatic splanchnic tissues drained by the portal vein.

During exercise arterial ananine rose 20-25% with mild exertion and 60-96% at the heavier work loads. Both at rest and during exercise a direct correlation was observed between arterial alanine and arterial pyruvate levels. Net amino acid release across the exercising leg was consistently observed at all levels of work intensity only for alanine. Estimated leg alanine output increased above resting levels in proportion to the work load. Splanchnic alanine uptake during exercise exceeded that of all other amino acids and increased by 15-20% during mild and moderate exercise, primarily as a consequence of augmented fractional extraction of alanine. For all other amino acids, there was no change in arterial concentration during mild exercise. At heavier work loads, increases of 8-35% were noted for isoleucine, leucine, methionine, tyrosine, and phenylalanine, which were attributable to altered splanchnic exchange rather than augmented peripheral release.

The data suggest that (a) synthesis of alanine in muscle, presumably by transamination of glucose-derived pyruvate, is increased in exercise probably as a consequence of increased availability of pyruvate and amino groups; (b) circulating alanine serves an important carrier function in the transport of amino groups from peripheral muscle to the liver, particularly during exercise; (c) a glucose-alanine cycle exists whereby alanine, synthesized in muscle, is taken up by the liver and its glucose-derived carbon skeleton is reconverted to glucose.

Full text

PDF
2703

Images in this article

2712Image
on p.2712

Selected References

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

  1. Bowman R. H. Effects of diabetes, fatty acids, and ketone bodies on tricarboxylic acid cycle metabolism in the perfused rat heart. J Biol Chem. 1966 Jul 10;241(13):3041–3048. [PubMed] [Google Scholar]
  2. Brosnan J. T., Krebs H. A., Williamson D. H. Effects of ischaemia on metabolite concentrations in rat liver. Biochem J. 1970 Mar;117(1):91–96. doi: 10.1042/bj1170091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. CARLSTEN A., HALLGREN B., JAGENBUR G. R., SVANBORG A., WERKO L. Arterial concentrations of free fatty acids and free amino acids in healthy human individuals at rest and at different work loads. Scand J Clin Lab Invest. 1962;14:185–191. doi: 10.3109/00365516209079692. [DOI] [PubMed] [Google Scholar]
  4. CARLSTEN A., HALLGREN B., JAGENBURG R., SVANBORG A., WERKO L. Myocardial metabolism of glucose, lactic acid, amino acids and fatty acids in healthy human individuals at rest and at different work loads. Scand J Clin Lab Invest. 1961;13:418–428. [PubMed] [Google Scholar]
  5. Carlsten A., Hallgren B., Jagenburg R., Svanborg A., Werkö L. Arterio-hepatic venous differences of free fatty acids and amino acids. Studies in patients with diabetes or essential hypercholesterolemia, and in healthy individuals. Acta Med Scand. 1967 Feb;181(2):199–207. doi: 10.1111/j.0954-6820.1967.tb07246.x. [DOI] [PubMed] [Google Scholar]
  6. Felig P., Owen O. E., Wahren J., Cahill G. F., Jr Amino acid metabolism during prolonged starvation. J Clin Invest. 1969 Mar;48(3):584–594. doi: 10.1172/JCI106017. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Felig P., Pozefsky T., Marliss E., Cahill G. F., Jr Alanine: key role in gluconeogenesis. Science. 1970 Feb 13;167(3920):1003–1004. doi: 10.1126/science.167.3920.1003. [DOI] [PubMed] [Google Scholar]
  8. Felig P., Wahren J. Influence of endogenous insulin secretion on splanchnic glucose and amino acid metabolism in man. J Clin Invest. 1971 Aug;50(8):1702–1711. doi: 10.1172/JCI106659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. KEUL J., DOLL E., STEIM H., SINGER U., REINDELL H. UBER DEN STOFFWECHSEL DES MENSCHLICHEN HERZENS. DAS VERHALTEN DER ARTERIOCORONARVENOESEN DIFFERENZEN DER AMINOSAEUREN UND DES AMMONIAK BEIM GESUNDEN, MENSCHLICHEN HERZEN IN RUHE, WAEHREND UND NACH KOERPERLICHER ARBEIT. Dtsch Arch Klin Med. 1964 Nov 30;209:717–725. [PubMed] [Google Scholar]
  10. KOMINZ D. R., HOUGH A., SYMONDS P., LAKI K. The amino acid composition of action, myosin, tropomyosin and the meromyosins. Arch Biochem Biophys. 1954 May;50(1):148–159. doi: 10.1016/0003-9861(54)90017-x. [DOI] [PubMed] [Google Scholar]
  11. Levin B., Oberholzer V. G., Sinclair L. Biochemical investigations of hyperammonaemia. Lancet. 1969 Jul 26;2(7613):170–174. doi: 10.1016/s0140-6736(69)91419-6. [DOI] [PubMed] [Google Scholar]
  12. Lonsdale D., Faulkner W. R., Price J. W., Smeby R. R. Intermittent cerebellar ataxia associated with hyperpyruvic acidemia, hyperalaninemia, and hyperalaninuria. Pediatrics. 1969 Jun;43(6):1025–1034. [PubMed] [Google Scholar]
  13. Lowenstein J., Tornheim K. Ammonia production in muscle: the purine nucleotide cycle. Science. 1971 Jan 29;171(3969):397–400. doi: 10.1126/science.171.3969.397. [DOI] [PubMed] [Google Scholar]
  14. Mallet L. E., Exton J. H., Park C. R. Control of gluconeogenesis from amino acids in the perfused rat liver. J Biol Chem. 1969 Oct 25;244(20):5713–5723. [PubMed] [Google Scholar]
  15. Malmquist J., Jagenburg R., Lindstedt G. Familial protein intolerance. Possible nature of enzyme defect. N Engl J Med. 1971 May 6;284(18):997–1002. doi: 10.1056/NEJM197105062841802. [DOI] [PubMed] [Google Scholar]
  16. Marliss E. B., Aoki T. T., Pozefsky T., Most A. S., Cahill G. F., Jr Muscle and splanchnic glutmine and glutamate metabolism in postabsorptive andstarved man. J Clin Invest. 1971 Apr;50(4):814–817. doi: 10.1172/JCI106552. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Mohyuddin F., Rathbun J. C., McMurray W. C. Studies on amino acid metabolism in citrullinuria. Am J Dis Child. 1967 Jan;113(1):152–156. doi: 10.1001/archpedi.1967.02090160202033. [DOI] [PubMed] [Google Scholar]
  18. Pozefsky T., Felig P., Tobin J. D., Soeldner J. S., Cahill G. F., Jr Amino acid balance across tissues of the forearm in postabsorptive man. Effects of insulin at two dose levels. J Clin Invest. 1969 Dec;48(12):2273–2282. doi: 10.1172/JCI106193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Randle P. J., England P. J., Denton R. M. Control of the tricarboxylate cycle and its interactions with glycolysis during acetate utilization in rat heart. Biochem J. 1970 May;117(4):677–695. doi: 10.1042/bj1170677. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ross B. D., Hems R., Krebs H. A. The rate of gluconeogenesis from various precursors in the perfused rat liver. Biochem J. 1967 Mar;102(3):942–951. doi: 10.1042/bj1020942. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rowell L. B., Kraning K. K., 2nd, Evans T. O., Kennedy J. W., Blackmon J. R., Kusumi F. Splanchnic removal of lactate and pyruvate during prolonged exercise in man. J Appl Physiol. 1966 Nov;21(6):1773–1783. doi: 10.1152/jappl.1966.21.6.1773. [DOI] [PubMed] [Google Scholar]
  22. SCHWARTZ A. E., LAWRENCE W., Jr, ROBERTS K. E. Elevation of peripheral blood ammonia following muscular exercise. Proc Soc Exp Biol Med. 1958 Jul;98(3):548–550. doi: 10.3181/00379727-98-24103. [DOI] [PubMed] [Google Scholar]
  23. STEIN W. H., MOORE S. The free amino acids of human blood plasma. J Biol Chem. 1954 Dec;211(2):915–926. [PubMed] [Google Scholar]
  24. Shih V. E., Efron M. L., Moser H. W. Hyperornithinemia, hyperammonemia, and homocitrullinuria. A new disorder of amino acid metabolism associated with myoclonic seizures and mental retardation. Am J Dis Child. 1969 Jan;117(1):83–92. [PubMed] [Google Scholar]
  25. Wahren J., Felig P., Ahlborg G., Jorfeldt L. Glucose metabolism during leg exercise in man. J Clin Invest. 1971 Dec;50(12):2715–2725. doi: 10.1172/JCI106772. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES