In silico analysis of exercise intolerance in myalgic encephalomyelitis/chronic fatigue syndrome

Biophysical Chemistry

Volumn 202, Issue , 2015, Pages 21-31

  Lengert, Nicor ^a   Drossel, Barbara ^a  

^a DARMSTADT UNIVERSITY OF TECHNOLOGY   (Germany)

Author keywords

ATP synthesis; Chronic fatigue syndrome; Exercise intolerance; Exercise recovery; Myalgic encephalomyelitis; Post exertional malaise

Indexed keywords

ADENINE NUCLEOTIDE; ADENOSINE TRIPHOSPHATE;

ARTICLE; CELL DEATH; CHRONIC FATIGUE SYNDROME; COMPUTER MODEL; CONCENTRATION (PARAMETERS); CONTROLLED STUDY; ENERGY RESOURCE; EXERCISE; EXERCISE INTOLERANCE; HUMAN; METABOLITE; MUSCLE METABOLISM; OXIDATIVE STRESS; PRIORITY JOURNAL; SKELETAL MUSCLE; TIME; COMPUTER SIMULATION; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY;

ADENOSINE TRIPHOSPHATE; COMPUTER SIMULATION; EXERCISE; FATIGUE SYNDROME, CHRONIC; HUMANS; MUSCLE, SKELETAL;

EID: 84927711115     PISSN: 03014622     EISSN: 18734200     Source Type: Journal    
DOI: 10.1016/j.bpc.2015.03.009     Document Type: Article

References (89)

1. D.E. Jones, K.G. Hollingsworth, D.G. Jakovljevic, G. Fattakhova, J. Pairman, A.M. Blamire, M.I. Trenell, and J.L. Newton Loss of capacity to recover from acidosis on repeat exercise in chronic fatigue syndrome: a case-control study Eur. J. Clin. Investig. 42 2 2012 186 194 10.1111/j.1365-2362.2011.02567.x
2. K.K. McCully, B.H. Natelson, S. Iotti, S. Sisto, and J.S. Leigh Reduced oxidative muscle metabolism in chronic fatigue syndrome Muscle Nerve 19 5 1996 621 625 10.1002/(sici)1097-4598(199605)19:5<621::aid-mus10>3.3.co;2-c
3. K.K. McCully, and B.H. Natelson Impaired oxygen delivery to muscle in chronic fatigue syndrome Clin. Sci. 97 1999 603 608 10.1042/cs19980372
4. R.J. Lane, M.C. Barrett, D.J. Taylor, G.J. Kemp, and R. Lodi Heterogeneity in chronic fatigue syndrome: evidence from magnetic resonance spectroscopy of muscle Neuromuscul. Disord. 8 3 1998 204 209 10.1016/s0960-8966(98)00021-2
5. S. Myhill, N.E. Booth, and J. McLaren-Howard Chronic fatigue syndrome and mitochondrial dysfunction Int. J. Clin. Exp. Med. 2 1 2009 1
6. N.E. Booth, S. Myhill, and J. McLaren-Howard Mitochondrial dysfunction and the pathophysiology of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) Int. J. Clin. Exp. Med. 5 3 2012 208
7. S. Fulle, P. Mecocci, G. Fanó, I. Vecchiet, A. Vecchini, D. Racciotti, A. Cherubini, E. Pizzigallo, L. Vecchiet, U. Senin, and M.F. Beal Specific oxidative alterations in vastus lateralis muscle of patients with the diagnosis of chronic fatigue syndrome Free Radic. Biol. Med. 29 12 2000 1252 1259 10.1016/s0891-5849(00)00419-6
8. G. Kennedy, V.A. Spence, M. McLaren, A. Hill, C. Underwood, and J.J. Belch Oxidative stress levels are raised in chronic fatigue syndrome and are associated with clinical symptoms Free Radic. Biol. Med. 39 5 2005 584 589 10.1016/j.freeradbiomed.2005.04.020
9. R. Richards, T. Roberts, N. McGregor, R. Dunstan, and H. Butt Blood parameters indicative of oxidative stress are associated with symptom expression in chronic fatigue syndrome Redox Rep. 5 1 2000 35 41 10.1179/rer.2000.5.1.35
10. J. Van Oosterwijck, J. Nijs, M. Meeus, I. Lefever, L. Huybrechts, L. Lambrecht, and L. Paul Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study J. Intern. Med. 268 3 2010 265 278 10.1111/j.1365-2796.2010.02228.x
11. J.M. VanNess, S.R. Stevens, L. Bateman, T.L. Stiles, and C.R. Snell Postexertional malaise in women with chronic fatigue syndrome J. Women's Health 19 2 2010 239 244 10.1089/jwh.2009.1507
12. Y. Jammes, J. Steinberg, O. Mambrini, F. Bregeon, and S. Delliaux Chronic fatigue syndrome: assessment of increased oxidative stress and altered muscle excitability in response to incremental exercise J. Intern. Med. 257 3 2005 299 310 10.1111/j.1365-2796.2005.01452.x
13. C. Zhang, A. Baumer, I.R. Mackay, A.W. Linnane, and P. Nagley Unusual pattern of mitochondrial dna deletions in skeletal muscle of an adult human with chronic fatigue syndrome Hum. Mol. Genet. 4 4 1995 751 754 10.1093/hmg/4.4.751
14. J.M. VanNess, C.R. Snell, D.R. Strayer, L. Dempsey, and S.R. Stevens Subclassifying chronic fatigue syndrome through exercise testing Med. Sci. Sports Exerc. 35 6 2003 908 913 10.1249/01.mss.0000069510.58763.e8
15. F. Twisk, and M. Maes A review on cognitive behavorial therapy (CBT) and graded exercise therapy (get) in myalgic encephalomyelitis (ME)/chronic fatigue syndrome (CFS): CBT/GET is not only ineffective and not evidence-based, but also potentially harmful for many patients with ME/CFS Neuroendocrinol. Lett. 30 3 2008 284 299
16. T. Kindlon Reporting of harms associated with graded exercise therapy and cognitive behavioural therapy in myalgic encephalomyelitis/chronic fatigue syndrome Bull. IACFS/ME 19 2 2011 59 111
17. M. Núñez, J. Fernández-Solà, E. Nuñez, J.-M. Fernández-Huerta, T. Godás-Sieso, and E. Gomez-Gil Health-related quality of life in patients with chronic fatigue syndrome: group cognitive behavioural therapy and graded exercise versus usual treatment. A randomised controlled trial with 1 year of follow-up Clin. Rheumatol. 30 3 2011 381 389 10.1007/s10067-010-1677-y
18. A.R. Light, A.T. White, R.W. Hughen, and K.C. Light Moderate exercise increases expression for sensory, adrenergic, and immune genes in chronic fatigue syndrome patients but not in normal subjects J. Pain 10 10 2009 1099 1112 10.1016/j.jpain.2009.06.003
19. A.T. White, A.R. Light, R.W. Hughen, T.A. VanHaitsma, and K.C. Light Differences in metabolite-detecting, adrenergic, and immune gene expression after moderate exercise in patients with chronic fatigue syndrome, patients with multiple sclerosis, and healthy controls Psychosom. Med. 74 1 2012 46 54 10.1097/PSY.0b013e31824152ed
20. K. Fukuda, S.E. Straus, I. Hickie, M.C. Sharpe, J.G. Dobbins, and A. Komaroff The chronic fatigue syndrome: a comprehensive approach to its definition and study Ann. Intern. Med. 121 12 1994 953 959 10.7326/0003-4819-121-12-199412150-00009
21. B.M. Carruthers, A.K. Jain, K.L. De Meirleir, D.L. Peterson, N.G. Klimas, A.M. Lerner, A.C. Bested, P. Flor-Henry, P. Joshi, and A.P. Powles Myalgic encephalomyelitis/chronic fatigue syndrome: clinical working case definition, diagnostic and treatment protocols J. Chronic Fatigue Syndr. 11 1 2003 7 115
22. E.W. Clayton Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: An IOM Report on Redefining an Illness 2015 Institute of Medicine of the National Academies
23. C.R. Snell, S.R. Stevens, T.E. Davenport, and J.M. Van Ness Discriminative validity of metabolic and workload measurements for identifying people with chronic fatigue syndrome Theor. Biol. Med. Model. 93 11 2013 1484 1492 10.2522/ptj.20110368
24. J.M. VanNess, C.R. Snell, S.R. Stevens, L. Bateman, and B.A. Keller Using serial cardiopulmonary exercise tests to support a diagnosis of chronic fatigue syndrome Med. Sci. Sports Exerc. 38 5 2006 S85 10.1249/00005768-200605001-00386
25. D. Arnold, G. Radda, P. Bore, P. Styles, and D. Taylor Excessive intracellular acidosis of skeletal muscle on exercise in a patient with a post-viral exhaustion/fatigue syndrome: a 31p nuclear magnetic resonance study Lancet 323 8391 1984 1367 1369 10.1016/S0140-6736(84)91871-3
26. S.D. Vernon, T. Whistler, B. Cameron, I.B. Hickie, W.C. Reeves, and A. Lloyd Preliminary evidence of mitochondrial dysfunction associated with post-infective fatigue after acute infection with epstein barr virus BMC Infect. Dis. 6 1 2006 15
27. P. Englebienne, and K. De Meirleir Chronic Fatigue Syndrome: A Biological Approach 2002 CRC Press 10.1201/9781420041002
28. Y.-j. Geng, G.K. Hansson, and E. Holme Interferon-gamma and tumor necrosis factor synergize to induce nitric oxide production and inhibit mitochondrial respiration in vascular smooth muscle cells Circ. Res. 71 5 1992 1268 1276 10.1161/01.res.71.5.1268
29. J. Nijs, M. Meeus, N.R. McGregor, R. Meeusen, G. de Schutter, E. van Hoof, and K. De Meirleir Chronic fatigue syndrome: exercise performance related to immune dysfunction Med. Sci. Sports Exerc. 37 10 2005 1647 10.1249/01.mss.0000181680.35503.ce
30. B. Korzeniewski, and J.A. Zoladz A model of oxidative phosphorylation in mammalian skeletal muscle Biophys. Chem. 92 1 2001 17 34 10.1016/s0301-4622(01)00184-3
31. B. Korzeniewski, and P. Liguzinski Theoretical studies on the regulation of anaerobic glycolysis and its influence on oxidative phosphorylation in skeletal muscle Biophys. Chem. 110 1 2004 147 169 10.1016/j.bpc.2004.01.011
32. B. Korzeniewski, V. Deschodt-Arsac, G. Calmettes, J. Franconi, and P. Diolez Physiological heart activation by adrenaline involves parallel activation of ATP usage and supply Biochem. J. 413 2008 343 347 10.1042/bj20080162
33. B. Korzeniewski Regulation of oxidative phosphorylation in different muscles and various experimental conditions Biochem. J. 375 2003 799 804 10.1042/bj20030882
34. M. Vendelin, O. Kongas, and V. Saks Regulation of mitochondrial respiration in heart cells analyzed by reaction-diffusion model of energy transfer Am. J. Physiol. Cell Physiol. 278 4 2000 C747 C764
35. S. Matsuoka, N. Sarai, H. Jo, and A. Noma Simulation of ATP metabolism in cardiac excitation-contraction coupling Prog. Biophys. Mol. Biol. 85 2 2004 279 299 10.1016/j.pbiomolbio.2004.01.006
36. J.M. Berg, J.L. Tymoczko, and L. Stryer Biochemistry 5th edition 2002
37. A. Raggi, and M. Ranieri-Raggi Regulatory properties of AMP deaminase isoenzymes from rabbit red muscle Biochem. J. 242 1987 875 879
38. T.J. Wheeler, and J.M. Lowenstein Adenylate deaminase from rat muscle. Regulation by purine nucleotides and orthophosphate in the presence of 150 mm KCl J. Biol. Chem. 254 18 1979 8994 8999
39. Y. Hellsten, E.A. Richter, B. Kiens, and J. Bangsbo AMP deamination and purine exchange in human skeletal muscle during and after intense exercise J. Physiol. 520 3 1999 909 920 10.1111/j.1469-7793.1999.00909.x
40. K.W. Rundell, P.C. Tullson, and R.L. Terjung Altered kinetics of AMP deaminase by myosin binding Am. J. Physiol. 263 1992 C294 C299
41. K.W. Rundell, P.C. Tullson, and R.L. Terjung AMP deaminase binding in contracting rat skeletal muscle Am. J. Physiol. 263 1992 C287 C293 10.1249/00005768-199004000-00038
42. Y. Hellsten, B. Sjödin, E.A. Richter, and J. Bangsbo Urate uptake and lowered ATP levels in human muscle after high-intensity intermittent exercise Am. J. Physiol. Endocrinol. Metab. 274 4 1998 E600 E606
43. M.A. Febbraio, and J. Dancey Skeletal muscle energy metabolism during prolonged, fatiguing exercise J. Appl. Physiol. 87 6 1999 2341 2347
44. I.H. Fox, and W.N. Kelley Human phosphoribosylpyrophosphate synthetase distribution, purification, and properties J. Biol. Chem. 246 18 1971 5739 5748
45. G. Van den Berghe, F. Bontemps, M. Vincent, and F. Van den Bergh The purine nucleotide cycle and its molecular defects Prog. Neurobiol. 39 5 1992 547 561 10.1016/0301-0082(92)90006-z
46. T. Borza, C.V. Iancu, E. Pike, R.B. Honzatko, and H.J. Fromm Variations in the response of mouse isozymes of adenylosuccinate synthetase to inhibitors of physiological relevance J. Biol. Chem. 278 9 2003 6673 6679 10.1074/jbc.M210838200
47. T.W. Traut Physiological concentrations of purines and pyrimidines Mol. Cell. Biochem. 140 1 1994 1 22 10.1007/bf00928361
48. T. Spector, and R.L. Miller Mammalian adenylosuccinate synthetase: nucleotide monophosphate substrates and inhibitors Biochim. Biophys. Acta (BBA) Enzymol. 445 2 1976 509 517
49. Y. Matsuda, H. Ogawa, S. Fukutome, H. Shiraki, and H. Nakagawa Adenylosuccinate synthetase in rat liver: the existence of two types and their regulatory roles Biochem. Biophys. Res. Commun. 78 2 1977 766 771 10.1016/0006-291x(77)90245-5
50. H. Ogawa, H. Shiraki, Y. Matsuda, K. Kakiuchu, and H. Nakagawa Purification, crystallization, and properties of adenylosuccinate synthetase from rat skeletal muscle J. Biochem. 81 4 1977 859 869
51. R.A. Robergs, F. Ghiasvand, and D. Parker Biochemistry of exercise-induced metabolic acidosis Am. J. Physiol. Regul. Integr. Comp. Physiol. 287 3 2004 R502 R516 10.1152/ajpregu.00114.2004
52. M.L. Parolin, A. Chesley, M.P. Matsos, L.L. Spriet, N.L. Jones, and G.J. Heigenhauser Regulation of skeletal muscle glycogen phosphorylase and PDH during maximal intermittent exercise Am. J. Physiol. 277 5 Pt 1 1999 E890 E900
53. G. Walter, K. Vandenborne, M. Elliott, and J.S. Leigh In vivo ATP synthesis rates in single human muscles during high intensity exercise J. Physiol. 519 Pt 3 1999 901 910 10.1111/j.1469-7793.1999.0901n.x
54. M. Hargreaves, M.J. McKenna, D.G. Jenkins, S.A. Warmington, J.L. Li, R.J. Snow, and M.A. Febbraio Muscle metabolites and performance during high-intensity, intermittent exercise J. Appl. Physiol. 84 5 1998 1687 1691
55. B. Norman, R.L. Sabina, and E. Jansson Regulation of skeletal muscle ATP catabolism by AMPD1 genotype during sprint exercise in asymptomatic subjects J. Appl. Physiol. 91 1 2001 258 264
56. P.C. Tullson, J. Bangsbo, Y. Hellsten, and E.A. Richter Metabolism in human skeletal muscle after exhaustive exercise J. Appl. Physiol. 78 1 1995 146 152
57. S. Zhao, R. Snow, C. Stathis, M. Febbraio, and M. Carey Muscle adenine nucleotide metabolism during and in recovery from maximal exercise in humans J. Appl. Physiol. 88 5 2000 1513 1519
58. G.C. Bogdanis, M.E. Nevill, L.H. Boobis, H. Lakomy, and A.M. Nevill Recovery of power output and muscle metabolites following 30 s of maximal sprint cycling in man J. Physiol. 482 Pt 2 1995 467 480 10.1113/jphysiol.1995.sp020533
59. Z. Argov, N. De Stefano, T. Taivassalo, J. Chen, G. Karpati, and D. Arnold Abnormal oxidative metabolism in exercise intolerance of undetermined origin Neuromuscul. Disord. 7 2 1997 99 104 10.1016/S0960-8966(97)00426-4
60. P.C. Tullson, and R.L. Terjung Adenine nucleotide synthesis in exercising and endurance-trained skeletal muscle Am. J. Physiol. 261 2 Pt 1 1991 C342 C347
61. T.E. Graham, J. Bangsbo, P.D. Gollnick, C. Juel, and B. Saltin Ammonia metabolism during intense dynamic exercise and recovery in humans Am. J. Physiol. 259 2 Pt 1 1990 E170 E176
62. J.a. Zoladz, B. Korzeniewski, P. Kulinowski, J. Zapart-Bukowska, J. Majerczak, and A. Jasinski Phosphocreatine recovery overshoot after high intensity exercise in human skeletal muscle is associated with extensive muscle acidification and a significant decrease in phosphorylation potential J. Physiol. Sci. 60 5 2010 331 341 10.1007/s12576-010-0101-3
63. L.L. Spriet, M.I. Lindinger, R.S. McKelvie, G.J. Heigenhauser, and N.L. Jones Muscle glycogenolysis and H + concentration during maximal intermittent cycling J. Appl. Physiol. 66 1 1989 8 13
64. Y. Hellsten, L. Skadhauge, and J. Bangsbo Effect of ribose supplementation on resynthesis of adenine nucleotides after intense intermittent training in humans Am. J. Physiol. Regul. Integr. Comp. Physiol. 286 1 2004 R182 R188 10.1152/ajpregu.00286.2003
65. Y. Hellsten-Westing, B. Norman, P.D. Balsom, and B. Sjödin Decreased resting levels of adenine nucleotides in human skeletal muscle after high-intensity training J. Appl. Physiol. 74 1993 2523 2528
66. P.C. Tullson, H.B. John-Alder, D.A. Hood, and R.L. Terjung De novo synthesis of adenine nucleotides in different skeletal muscle fiber types Am. J. Physiol. 255 3 Pt 1 1988 C271 C277
67. J. Jeneson, H. Westerhoff, T. Brown, C. Van Echteld, and R. Berger Quasi-linear relationship between Gibbs free energy of ATP hydrolysis and power output in human forearm muscle Am. J. Physiol. Cell Physiol. 37 6 1995 C1474
68. L. Paul, L. Wood, W.M. Behan, and W.M. Maclaren Demonstration of delayed recovery from fatiguing exercise in chronic fatigue syndrome Eur. J. Neurol. 6 1 1999 63 69 10.1046/j.1468-1331.1999.610063.x
69. K. Sahlin, R.C. Harris, and E. Hultman Creatine kinase equilibrium and lactate content compared with muscle pH in tissue samples obtained after isometric exercise Biochem. J. 152 1975 173 180
70. L. Zhou, M.E. Cabrera, H. Huang, C.L. Yuan, D.K. Monika, N. Sharma, F. Bian, and W.C. Stanley Parallel activation of mitochondrial oxidative metabolism with increased cardiac energy expenditure is not dependent on fatty acid oxidation in pigs J. Physiol. 579 Pt 3 2007 811 821 10.1113/jphysiol.2006.123828
71. P.R. Territo, S.A. French, M.C. Dunleavy, F.J. Evans, and R.S. Balaban Calcium activation of heart mitochondrial oxidative phosphorylation rapid kinetics of mVO2, NADH, and light scattering J. Biol. Chem. 276 4 2001 2586 2599 10.1074/jbc.m002923200
72. D.S. Izyumov, A.V. Avetisyan, O.Y. Pletjushkina, D.V. Sakharov, K.W. Wirtz, B.V. Chernyak, and V.P. Skulachev "Wages of fear": transient threefold decrease in intracellular ATP level imposes apoptosis Biochim. Biophys. Acta (BBA) Bioenerg. 1658 1 2004 141 147 10.1016/j.bbabio.2004.05.007
73. J.E. Teitelbaum, C. Johnson, and J.S. Cyr The use of d-ribose in chronic fatigue syndrome and fibromyalgia: a pilot study J. Altern. Complement. Med. 12 9 2006 857 862 10.1089/acm.2006.12.857
74. Y. Wei, L. Chen, J. Chen, L. Ge, and R.Q. He Rapid glycation with d-ribose induces globular amyloid-like aggregations of BSA with high cytotoxicity to SH-SY5Y cells BMC Cell Biol. 10 1 2009 10 10.1186/1471-2121-10-10
75. S. Myhill, N.E. Booth, and J. McLaren-Howard Targeting mitochondrial dysfunction in the treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) - a clinical audit Int. J. Clin. Exp. Med. 6 1 2013 1
76. L.M. Forsyth, H.G. Preuss, A.L. MacDowell, L. Chiazze Jr., G.D. Birkmayer, and J.A. Bellanti Therapeutic effects of oral NADH on the symptoms of patients with chronic fatigue syndrome Ann. Allergy Asthma Immunol. 82 2 1999 185 191 10.1016/s1081-1206(10)62595-1
77. E. Borgonovo A new uncertainty importance measure Reliab. Eng. Syst. Saf. 92 6 2007 771 784 10.1016/j.ress.2006.04.015
78. E. Plischke, E. Borgonovo, and C.L. Smith Global sensitivity measures from given data Eur. J. Oper. Res. 226 3 2013 536 550 10.1016/j.ejor.2012.11.047
79. D.F. Rolfe, and M.D. Brand Contribution of mitochondrial proton leak to skeletal muscle respiration and to standard metabolic rate Am. J. Physiol. Cell Physiol. 40 4 1996 C1380
80. M.T. Bauschjurken, and R.L. Sabina Divergent n-terminal regions in AMP deaminase and isoform-specific catalytic properties of the enzyme Arch. Biochem. Biophys. 321 2 1995 372 380
81. C.T. Caskey, D.M. Ashton, and J.B. Wyngaarden The enzymology of feedback inhibition of glutamine phosphoribosylpyrophosphate amidotransferase by purine ribonucleotides J. Biol. Chem. 239 8 1964 2570 2579
82. K. Sahlin, R. Harris, B. Nylind, and E. Hultman Lactate content and pH in muscle samples obtained after dynamic exercise Pflugers Arch. 367 2 1976 143 149 10.1007/bf00585150
83. G.J. Kemp, M. Roussel, D. Bendahan, Y.L. Fur, and P.J. Cozzone Interrelations of ATP synthesis and proton handling in ischaemically exercising human forearm muscle studied by 31P magnetic resonance spectroscopy J. Physiol. 535.3 2001 901 928 10.1111/j.1469-7793.2001.00901.x
84. 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. 290 6 2006 E1180 E1190 10.1152/ajpendo.00499.2005
85. T.P.M. Akerboom, H. Bookelman, and P.F. Zuurendonk Intramitochondrial and extramitochondrial concentrations of adenine nucleotides and inorganic phosphate in isolated hepatocytes from fasted rats J. Biochem. 84 1978 413 420 10.1111/j.1432-1033.1978.tb12182.x
86. F. Brawand, G. Folly, and P. Walter Relation between extra- and intramitochondrial ATP/ADP ratios in rat liver mitochondria Biochim. Biophys. Acta 590 1979 285 289 10.1016/0005-2728(80)90199-1
87. E. Metelkin, O. Demin, Z. Kovács, and C. Chinopoulos Modeling of ATP-ADP steady-state exchange rate mediated by the adenine nucleotide translocase in isolated mitochondria FEBS J. 276 23 2009 6942 6955 10.1111/j.1742-4658.2009.07394.x
88. L. Miles, M.V. Miles, P.H. Tang, P.S. Horn, J.G. Quinlan, B. Wong, A. Wenisch, and K.E. Bove Ubiquinol: a potential biomarker for tissue energy requirements and oxidative stress Clin. Chim. Acta 360 1 2005 87 96 10.1016/j.cccn.2005.04.009
89. T. Kashiwagura, D.F. Wilson, and M. Erecińska Oxygen dependence of cellular metabolism: the effect of O2 tension on gluconeogenesis and urea synthesis in isolated rat hepatocytes J. Cell. Physiol. 120 1 1984 13 18 10.1002/jcp.1041200103