Pathways of purine metabolism: effects of exercise and training in competitive athletes
Treść / Zawartość
Introduction. The main part of skeletal muscle adenosine- 5'-triphosphate (ATP) is restored by inosine monophosphate (IMP) reamination in the purine nucleotide cycle. The intramuscular resources of IMP may be resynthesized via the quick and economical salvage pathway, in which muscle hypoxanthine (Hx) is reconverted to IMP by hypoxanthineguanine phosphoribosyl transferase (HGPRT). IMP is subsequently reutilized in the adenine nucleotide (AdN) pool. Inosine and Hx, which flow out of the skeletal muscle, represent the loss of AdN precursors. In the latter case, full restoration of resting ATP levels depends on a slow and energy-consuming de novo pathway. Plasma Hx and erythrocyte HGPRT are indirect indicators of muscle metabolism, particularly of AdN degradation, that reflect exercise- and training-induced muscle energy status. Results. Our analyses of long-term training cycles in different sports show that plasma Hx concentration and erythrocyte HGPRT activity significantly change in consecutive training phases. Both high-intensity sprint training and endurance training incorporating high-intensity exercise lead to a decrease in plasma Hx levels and an increase in erythrocyte HGPRT activity. The lowest Hx concentration and the highest HGPRT activity are observed in the competition phase characterised by low-volume and high-intensity training loads. Training cessation in the transition phase brings about a reverse phenomenon: an increase in Hx levels and a decrease in HGPRT activity. Conclusions. Low plasma purine levels indicate that the administered training adapts the athletes to high-intensity exercise (more economical AdN use, limited purine efflux from muscle into the blood). Such an adaptation is of great importance for contemporary elite athletes. Purine metabolites are more sensitive markers of training status and better performance predictors than typical biochemical and physiological indicators (e.g. blood lactate and oxygen uptake) in highly-trained athletes of different specializations and ages. The use of Hx and HGPRT for monitoring and control of the training process is worthy of consideration.
- 1. Balsom PB, Seger JY, Sjödin B, Ekblom B. Physiological response to maximal intensity intermittent exercise. Eur J Appl Physiol. 1992; 65: 144-149.
- 2. Bangsbo J, Sjödin B, Hellsten-Westing Y. Exchange of hypoxanthine in muscle during intense exercise in man. Acta Physiol Scand. 1992; 146: 549-550.
- 3. Bianchi GP, Grossi G, Bargossi AM, et al. Can oxypurines plasma levels classify the type of physical exercise? Sports Med Phys Fitness. 1999; 39: 123-127.
- 4. Bindoli A, Cavallini L, Rigobello MP, et al. Modification of the xanthine-converting enzyme of perfused rat heart during ischemia and oxidative stress. Free Radic Biol Med. 1988; 4: 163-167.
- 5. Borowiec A, Lechward K, Tkacz-Stachowka K, Składanowski AC. Adenosine as a metabolic regulator of tissue function: production of adenosine by cytoplasmic 5’-nucleotidases. Acta Biochim Pol. 2006; 53: 269-278.
- 6. Brault JJ and Terjung RL. Purine salvage to adenine nucleotides in different skeletal muscle fiber types. J Appl Physiol. 2001; 91: 231-238.
- 7. Cabrita MA, Baldwin SA, Young JD, Cass CE. Molecular biology and regulation of nucleoside and nucleobase transporter proteins in eukaryotes and prokaryotes. Biochem Cell Biol. 2002; 80: 623-638.
- 8. Corte ED, Stirpe F. The regulation of rat liver xanthine oxidase. Involvement of thiol groups in the conversion of the enzyme activity from dehydrogenase (type D) into oxidase (type O) and purification of the enzyme. Biochem J. 1972; 126: 739-745.
- 9. Edwards NL, Recker D, Fox IH. Overproduction of uric acid in hypoxanthine-guanine phosphoribosyltransferase deficiency. Contribution by impaired purine salvage. J Clin Invest. 1979; 63: 922-930.
- 10. Goodman MN, Löwenstein JM. The purine nucleotide cycle. Studies of ammonia production by skeletal muscle in situ and in perfused preparations. J Biol Chem. 1977; 252: 5054-5060.
- 11. Griffiths M, Yao SY, Abidi F, et al. Molecular cloning and characterization of a nitrobenzylthioinosineinsensitive (ei) equilibrative nucleoside transporter from human placenta. Biochem J. 1997; 328: 739-743.
- 12. Han DH, Hansen PA, Nolte LA, Holloszy JO. Removal of adenosine decreases the responsiveness of muscle glucose transport to insulin and contractions. Diabetes. 1998; 47: 1671-1675.
- 13. Hargreaves M, McKenna MJ, Jenkins DG, et al. Muscle metabolites and performance during high-intensity, intermittent exercise. J Appl Physiol. 1998; 84: 1687- 1691.
- 14. Harkness RA, Simmonds RJ, Coade SB. Purine transport and metabolism in man: the effect of exercise on concentrations of purine bases, nucleosides and nucleotides in plasma urine, leucocytes and erythrocytes. Clin Sci. 64: 1983; 333-340.
- 15. Harmsen E, de Tombe PP, de Jong JW, Achterberg PW. Enhanced ATP and GTP synthesis from hypoxanthine or inosine after myocardial ischemia. Am J Physiol. 1984; 246: H37-H43.
- 16. Hellsten Y, Richter EA, Kiens B, Bangsbo J. AMP deamination and purine exchange in human skeletal muscle during and after intense exercise. J Physiol. 1999; 520: 909-920.
- 17. Hellsten Y, Sjodin B, Richter EA, Bangsbo J. Urate uptake and lowered ATP levels in human muscle after high-intensity intermittent exercise. Am J Physiol. 1998; 274: E600-E606.
- 18. Hellsten Y, Skadhauge L, Bangsbo J. Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans. Am J Physiol Regul Integr Comp Physiol. 2004; 286: R182-R188.19. Hellsten-Westing Y, Balsom PD, Norman B, Sjödin B. The effect of high-intensity training on purine metabolism in man. Acta Physiol Scand. 1993; 149: 405-412.
- 20. Hellsten-Westing Y, Ekblom B, Sjödin B. The metabolic relation between hypoxanthine and uric acid in man following maximal short-distance running. Acta Physiol Scand. 1989; 137: 341-345.
- 21. Hellsten-Westing Y, Kaijser L, Ekblom B, Sjödin B. Exchange of purines in human liver and skeletal muscle with short-term exhaustive exercise. Am J Physiol Regul Integr Comp Physiol. 1994; 266: R81-R86.
- 22. Hellsten-Westing Y, Norman B, Balsom PD, Sjödin B. Decreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity training. J Appl Physiol. 1993; 74: 2523-2528.
- 23. Hellsten-Westing Y, Sollevi A, Sjödin B. Plasma accumulation of hypoxanthine, uric acid and creatine kinase following exhausting runs of differing durations in man. Eur J Appl Physiol Occup Physiol. 1991; 62: 380-384.
- 24. Hyde RJ, Cass CE, Young JD, Baldwin SA. The ENT family of eukaryote nucleoside and nucleobase transporters: recent advances in the investigation of structure/function relationships and the identification of novel isoforms. Mol Membr Biol. 2001; 18: 53-63.
- 25. Jarasch ED, Grund C, Bruder G, et al. Localization of xanthine oxidase in mammary-gland epithelium and capillary endothelium. Cell. 1981; 25: 67-82.
- 26. Kaya M, Moriwaki Y, Ka T, et al. Plasma concentrations and urinary excretion of purine bases (uric acid, hypoxanthine, and xanthine) and oxypurinol after rigorous exercise. Metabolism. 2006; 55: 103-107.
- 27. Ketai LH, Simon RH, Kreit JW, Grum CM. Plasma hypoxanthine and exercise. Am Rev Respir Dis. 1987; 136: 98-101.
- 28. Kim YA, King MT, Teague WE Jr, et al. Regulation of the purine salvage pathway in rat liver. Am J Physiol. 1992; 262: E344-E352.
- 29. Kono N, Mineo I, Shimizu T, et al. Increased plasma uric acid after exercise in muscle phosphofructokinase deficiency. Neurology. 1986; 36: 106-108.
- 30. Kuppusamy P, Zweier JL. Characterization of free radical generation by xanthine oxidase. Evidence for hydroxyl radical generation. J Biol Chem. 1989; 264: 9880-9884.
- 31. Löwenstein JM. Ammonia production in muscle and other tissues: the purine nucleotide cycle. Physiol Rev. 1972; 52: 382-414.
- 32. Lynge J, Juel C, Hellsten Y. Extracellular formation and uptake of adenosine during skeletal muscle in the rat: role of adenosine transporters. J Physiol. 2001; 537: 597-605.
- 33. Manfredi JP, Holmes EW. Control of the purine nucleotide cycle in extracts of rat skeletal muscle: effects of energy state and concentrations of cycle intermediates. Arch Biochem Biophys. 1984; 233: 515-529.
- 34. Matthews CK, Van Holde KE. Biochemistry. Redwood City, CA: Benjamin Cummings; 1990.
- 35. Meyer RA, Terjung RL. AMP deamination and IMP reamination in working skeletal muscle. Am J Physiol Cell Physiol. 1980; 239: C32-C38.
- 36. Mineo I, Kono N, Shimizu T, et al. Excess purine degradation in exercising muscles of patients with glycogen storage disease types V and VII. J Clin Invest. 1985; 76: 556-560.
- 37. Namm DH. Myocardial nucleotide synthesis from purine bases and nucleosides. Comparison of the rates of formation of purine nucleotides from various precursors and identification of the enzymatic routes for nucleotide formation in the isolated rat heart. Circ Res. 1973; 33: 686-695.
- 38. Newsholme E, Leech A. Biochemistry for the medical sciences. New York: Wiley; 1983.
- 39. Norman B, Sabina RL, Jansson E. Regulation of skeletal muscle ATP catabolism by AMPD1 genotype during sprint exercise in asymptomatic subjects. J Appl Physiol. 2001; 91: 258-264.
- 40. Parks DA, Williams TK, Beckman JS. Conversion of xanthine dehydrogenase to oxidase in ischemic rat intestine: a reevaluation. Am J Physiol. 1988; 254: G768-G774.
- 41. Pennycooke M, Chaudary N, Shuralyova I, et al. Differential expression of human nucleoside transporters in normal and tumor tissue. Biochem Biophys Commun. 2001; 280: 951-995.
- 42. Plagemann PG, Wohlhueter RM. Hypoxanthine transport in mammalian cells: cell type-specific differences in sensitivity to inhibition by dipyridamole and uridine. J Membr Biol. 1984; 81: 255-262.
- 43. Rychlewski T, Banaszak F, Szczęśniak Ł, et al. Plasma hypoxanthine as an indicator of exercise intensity [in German, English summary]. Sportonomics. 1997; 1: 47-52.
- 44. Sabina RL, Swain JL, Olanow CW, et al. Myoadenylate deaminase deficiency. Functional and metabolic abnormalities associated with disruption of the purine nucleotide cycle. J Clin Invest. 1984; 73: 720-730.
- 45. Sahlin K, Broberg S. Adenine nucleotide depletion in human muscle during exercise: causality and significance of AMP deamination. Int J Sports Med. 1990; 11: S62-S67.
- 46. Sahlin K, Ekberg K, Cizinsky S. Changes in plasma hypoxanthine and free radical markers during exercise in man. Acta Physiol Scand. 1991; 142: 275-281.