Disturbed energy metabolism and muscular dystrophy caused by pure creatine deficiency are reversible by creatine intake

Journal of Physiology

Volumn 591, Issue 2, 2013, Pages 571-592

  Nabuurs, C I ^a   Choe, C U ^b   Veltien, A ^a   Kan, H E ^a   van Loon, L J C ^b   Rodenburg, R J T ^c   Matschke, J ^d   Wieringa, B ^d   Kemp, G J ^e   Isbrandt, D ^b   Heerschap, A ^a  

^a RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^b UNIVERSITY MEDICAL CENTER HAMBURG EPPENDORF   (Germany)

^c MAASTRICHT UNIVERSITY MEDICAL CENTER   (Netherlands)

^d RADBOUD UNIVERSITY MEDICAL CENTER   (Netherlands)

^e UNIVERSITY OF LIVERPOOL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ADENOSINE TRIPHOSPHATE; CREATINE; CREATINE KINASE; CREATINE PHOSPHATE; CYTOCHROME C OXIDASE; FAT DROPLET; GLYCINE AMIDINOTRANSFERASE; HYDROGEN POTASSIUM ADENOSINE TRIPHOSPHATASE; PHOSPHATE; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE); SUCCINATE DEHYDROGENASE; SUCCINATE DEHYDROGENASE (UBIQUINONE); UBIQUINOL CYTOCHROME C REDUCTASE;

AMINO ACID DEFICIENCY; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; CREATINE DEFICIENCY; CRYSTALLIZATION; DISEASE SEVERITY; DISORDERS OF MITOCHONDRIAL FUNCTIONS; ELECTRON MICROSCOPY; ENERGY BALANCE; ENERGY METABOLISM; ENZYME ACTIVITY; ENZYME DEFICIENCY; GLYCINE AMIDINOTRANSFERASE DEFICIENCY; GLYCOLYSIS; GRIP STRENGTH; HINDLIMB; IN VIVO STUDY; LEG MUSCLE; MALE; MITOCHONDRION; MOUSE; MUSCLE ATROPHY; MUSCLE CELL; MUSCLE ISCHEMIA; MUSCULAR DYSTROPHY; NONHUMAN; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PH; PRIORITY JOURNAL; REST; SKELETAL MUSCLE; TREATMENT OUTCOME; WILD TYPE;

ADENOSINE TRIPHOSPHATE; AMIDINOTRANSFERASES; AMINO ACID METABOLISM, INBORN ERRORS; ANIMALS; CREATINE; CREATINE KINASE; DEVELOPMENTAL DISABILITIES; ENERGY METABOLISM; HAND STRENGTH; HINDLIMB; HYDROGEN-ION CONCENTRATION; INTELLECTUAL DISABILITY; ISCHEMIA; LIPID METABOLISM; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MICE, KNOCKOUT; MITOCHONDRIA; MUSCLE FIBERS, SKELETAL; MUSCLE, SKELETAL; MUSCULAR ATROPHY; PHOSPHATES; PROTON-TRANSLOCATING ATPASES; SPEECH DISORDERS;

EID: 84872420412     PISSN: 00223751     EISSN: 14697793     Source Type: Journal    
DOI: 10.1113/jphysiol.2012.241760     Document Type: Article

References (97)

1. Acosta ML, Kalloniatis M & Christie DL (2005). Creatine transporter localization in developing and adult retina: importance of creatine to retinal function. Am J Physiol Cell Physiol 289, C1015-C1023.
2. Akima H, Lott D, Senesac C, Deol J, Germain S, Arpan I, Bendixen R, Lee Sweeney H, Walter G & Vandenborne K (2012). Relationships of thigh muscle contractile and non-contractile tissue with function, strength, and age in boys with Duchenne muscular dystrophy. Neuromuscul Disord 22, 16-25.
3. Battini R, Leuzzi V, Carducci C, Tosetti M, Bianchi MC, Item CB, Stöckler-Ipsiroglu S & Cioni G (2002). Creatine depletion in a new case with AGAT deficiency: clinical and genetic study in a large pedigree. Mol Genet Metab 77, 326-331.
4. Bergeron R, Previs SF, Cline GW, Perret P, Russell RR 3rd, Young LH & Shulman GI (2001). Effect of 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside infusion on in vivo glucose and lipid metabolism in lean and obese Zucker rats. Diabetes 50, 1076-1082.
5. 31P-MR spectroscopy study. AJNR Am J Neuroradiol 28, 548-554.
6. Bianchi MC, Tosetti M, Fornai F, Alessandri MG, Cipriani P, De Vito G & Canapicchi R (2000). Reversible brain creatine deficiency in two sisters with normal blood creatine level. Ann Neurol 47, 511-513.
7. Blei ML, Conley KE & Kushmerick MJ (1993). Separate measures of ATP utilization and recovery in human skeletal muscle. J Physiol 465, 203-222.
8. Boehm EA, Radda GK, Tomlin H & Clark JF (1996). The utilisation of creatine and its analogues by cytosolic and mitochondrial creatine kinase. Biochim Biophys Acta 1274, 119-128.
9. Bottomley PA (1987). Spatial localization in NMR spectroscopy in vivo. Ann N Y Acad Sci 508, 333-348.
10. Braissant O (2012). Creatine and guanidinoacetate transport at blood-brain and blood-cerebrospinal fluid barriers. J Inherit Metab Dis 35, 655-664.
11. Braissant O, Henry H, Loup M, Eilers B & Bachmann C (2001). Endogenous synthesis and transport of creatine in the rat brain: an in situ hybridization study. Brain Res Mol Brain Res 86, 193-201.
12. Choe CU, Nabuurs C, Stockebrand M, Neu A, Nunes P, Morellini F, Sauter K, Schillemeit S, Hermans-Borgmeyer I, Marescau B, Heerschap A & Isbrandt D (2012). L-Arginine:glycine amidinotransferase (AGAT) deficiency protects from metabolic syndrome. Hum Mol Genet DOI.
13. Clark JF, Khuchua Z, Kuznetsov AV, Vassil'eva E, Boehm E, Radda GK & Saks V (1994). Actions of the creatine analogue beta-guanidinopropionic acid on rat heart mitochondria. Biochem J 300, 211-216.
14. Cooperstein SJ & Lazarow A (1951). A microspectrophotometric method for the determination of cytochrome oxidase. J Biol Chem 189, 665-670.
15. Dahlstedt AJ, Katz A, Wieringa B & Westerblad H (2000). Is creatine kinase responsible for fatigue? Studies of isolated skeletal muscle deficient in creatine kinase. FASEB J 14, 982-990.
16. Das AM, Ullrich K & Isbrandt D (2000). Upregulation of respiratory chain enzymes in guanidinoacetate methyltransferase deficiency. J Inherit Metab Dis 23, 375-377.
17. Dechent P, Pouwels PJ, Wilken B, Hanefeld F & Frahm J (1999). Increase of total creatine in human brain after oral supplementation of creatine-monohydrate. Am J Physiol 277, R698-R704.
18. deGrauw TJ, Cecil KM, Byars AW, Salomons GS, Ball WS & Jakobs C (2003). The clinical syndrome of creatine transporter deficiency. Mol Cell Biochem 244, 45-48.
19. de Haan A, Koudijs JC, Wevers RA & Wieringa B (1995). The effects of MM-creatine kinase deficiency on sustained force production of mouse fast skeletal muscle. Exp Physiol 80, 491-494.
20. del Porto LA, Nicholson GA & Ketheswaren P (2010). Correlation between muscle atrophy on MRI and manual strength testing in hereditary neuropathies. J Clin Neurosci 17, 874-878.
21. Dyck JR, Kudo N, Barr AJ, Davies SP, Hardie DG & Lopaschuk GD (1999). Phosphorylation control of cardiac acetyl-CoA carboxylase by cAMP-dependent protein kinase and 5′-AMP activated protein kinase. Eur J Biochem 262, 184-190.
22. Ensenauer R, Thiel T, Schwab KO, Tacke U, Stöckler-Ipsiroglu S, Schulze A, Hennig J & Lehnert W (2004). Guanidinoacetate methyltransferase deficiency: differences of creatine uptake in human brain and muscle. Mol Genet Metab 82, 208-213.
23. Guerrero-Ontiveros ML & Wallimann T (1998). Creatine supplementation in health and disease. Effects of chronic creatine ingestion in vivo: down-regulation of the expression of creatine transporter isoforms in skeletal muscle. Mol Cell Biochem 184, 427-437.
24. +-dependent creatine transporter in rabbit brain, muscle, heart, and kidney. cDNA cloning and functional expression. J Biol Chem 268, 8418-8421.
25. Harris RC, Hultman E & Nordesjö LO (1974). Glycogen, glycolytic intermediates and high-energy phosphates determined in biopsy samples of musculus quadriceps femoris of man at rest. Methods and variance of values. Scand J Clin Lab Invest 33, 109-120.
26. Hayashi T, Hirshman MF, Fujii N, Habinowski SA, Witters LA & Goodyear LJ (2000). Metabolic stress and altered glucose transport: activation of AMP-activated protein kinase as a unifying coupling mechanism. Diabetes 49, 527-531.
27. Heerschap A, Kan HE, Nabuurs CI, Renema WK, Isbrandt D & Wieringa B (2007). In vivo magnetic resonance spectroscopy of transgenic mice with altered expression of guanidinoacetate methyltransferase and creatine kinase isoenzymes. Subcell Biochem 46, 119-148.
28. Hersch SM, Gevorkian S, Marder K, Moskowitz C, Feigin A, Cox M, Como P, Zimmerman C, Lin M, Zhang L, Ulug AM, Beal MF, Matson W, Bogdanov M, Ebbel E, Zaleta A, Kaneko Y, Jenkins B, Hevelone N, Zhang H, Yu H, Schoenfeld D, Ferrante R & Rosas HD (2006). Creatine in Huntington disease is safe, tolerable, bioavailable in brain and reduces serum 8OH2′dG. Neurology 66, 250-252.
29. Holmes BF, Kurth-Kraczek EJ & Winder WW (1999). Chronic activation of 5′-AMP-activated protein kinase increases GLUT-4, hexokinase, and glycogen in muscle. J Appl Physiol 87, 1990-1995.
30. Horn M, Frantz S, Remkes H, Laser A, Urban B, Mettenleiter A, Schnackerz K & Neubauer S (1998). Effects of chronic dietary creatine feeding on cardiac energy metabolism and on creatine content in heart, skeletal muscle, brain, liver and kidney. J Mol Cell Cardiol 30, 277-284.
31. in 't Zandt HJ, de Groof AJ, Renema WK, Oerlemans FT, Klomp DW, Wieringa B & Heerschap A (2003). Presence of (phospho)creatine in developing and adult skeletal muscle of mice without mitochondrial and cytosolic muscle creatine kinase isoforms. J Physiol 548, 847-858.
32. 31P nuclear magnetic resonance spectroscopy. NMR Biomed 12, 327-334.
33. 31P magnetic resonance study. J Neurochem 90, 1321-1330.
34. Ipsiroglu OS, Stromberger C, Ilas J, Höger H, Muhl A & Stöckler-Ipsiroglu S (2001). Changes of tissue creatine concentrations upon oral supplementation of creatine-monohydrate in various animal species. Life Sci 69, 1805-1815.
35. Janssen AJ, Trijbels FJ, Sengers RC, Smeitink JA, van den Heuvel LP, Wintjes LT, Stoltenborg-Hogenkamp BJ & Rodenburg RJ (2007). Spectrophotometric assay for complex I of the respiratory chain in tissue samples and cultured fibroblasts. Clin Chem 53, 729-734.
36. Jeneson JA, ter Veld F, Schmitz JP, Meyer RA, Hilbers PA & Nicolay K (2011). Similar mitochondrial activation kinetics in wild-type and creatine kinase-deficient fast-twitch muscle indicate significant Pi control of respiration. Am J Physiol Regul Integr Comp Physiol 300, R1316-R1325.
37. Jonckheere AI, Hogeveen M, Nijtmans LG, van den Brand MA, Janssen AJ, Diepstra JH, van den Brandt FC, van den Heuvel LP, Hol FA, Hofste TG, Kapusta L, Dillmann U, Shamdeen MG, Smeitink JA & Rodenburg RJ (2008). A novel mitochondrial ATP8 gene mutation in a patient with apical hypertrophic cardiomyopathy and neuropathy. J Med Genet 45, 129-133.
38. Juhn MS & Tarnopolsky M (1998). Potential side effects of oral creatine supplementation: a critical review. Clin J Sport Med 8, 298-304.
39. Kan HE, Buse-Pot TE, Peco R, Isbrandt D, Heerschap A & de Haan A (2005). Lower force and impaired performance during high-intensity electrical stimulation in skeletal muscle of GAMT-deficient knockout mice. Am J Physiol Cell Physiol 289, C113-C119.
40. Kan HE, Meeuwissen E, van Asten JJ, Veltien A, Isbrandt D & Heerschap A (2007). Creatine uptake in brain and skeletal muscle of mice lacking guanidinoacetate methyltransferase assessed by magnetic resonance spectroscopy. J Appl Physiol 102, 2121-2127.
41. Kan HE, Renema WK, Isbrandt D & Heerschap A (2004). Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase. J Physiol 560, 219-229.
42. 13C MR spectroscopy. Magn Reson Med 56, 953-957.
43. Kellner A, Matschke J, Bernreuther C, Moch H, Ferrer I & Glatzel M (2009). Autoantibodies against β-amyloid are common in Alzheimer's disease and help control plaque burden. Ann Neurol 65, 24-31.
44. 31P magnetic resonance spectroscopy. J Physiol 535, 901-928.
45. Kudo N, Barr AJ, Barr RL, Desai S & Lopaschuk GD (1995). High rates of fatty acid oxidation during reperfusion of ischemic hearts are associated with a decrease in malonyl-CoA levels due to an increase in 5′-AMP-activated protein kinase inhibition of acetyl-CoA carboxylase. J Biol Chem 270, 17513-17520.
46. Kushmerick MJ (1997). Multiple equilibria of cations with metabolites in muscle bioenergetics. Am J Physiol 272, C1739-C1747.
47. i. Proc Natl Acad Sci U S A 89, 7521-7525.
48. Low SY, Rennie MJ & Taylor PM (1996). Modulation of glycogen synthesis in rat skeletal muscle by changes in cell volume. J Physiol 495, 299-303.
49. Lyoo IK, Kong SW, Sung SM, Hirashima F, Parow A, Hennen J, Cohen BM & Renshaw PF (2003). Multinuclear magnetic resonance spectroscopy of high-energy phosphate metabolites in human brain following oral supplementation of creatine-monohydrate. Psychiatry Res 123, 87-100.
50. + accumulation in ischemic mouse muscle. J Appl Physiol 108, 1479-1486.
51. Marcinek DJ, Schenkman KA, Ciesielski WA & Conley KE (2004). Mitochondrial coupling in vivo in mouse skeletal muscle. Am J Physiol Cell Physiol 286, C457-C463.
52. Maughan RJ, Watson JS & Weir J (1983). Strength and cross-sectional area of human skeletal muscle. J Physiol 338, 37-49.
53. Meyer RA, Brown TR & Kushmerick MJ (1985). Phosphorus nuclear magnetic resonance of fast- and slow-twitch muscle. Am J Physiol 248, C279-C287.
54. Moerland TS, Wolf NG & Kushmerick MJ (1989). Administration of a creatine analogue induces isomyosin transitions in muscle. Am J Physiol 257, C810-C816.
55. Momken I, Lechene P, Koulmann N, Fortin D, Mateo P, Doan BT, Hoerter J, Bigard X, Veksler V & Ventura-Clapier R (2005). Impaired voluntary running capacity of creatine kinase-deficient mice. J Physiol 565, 951-964.
56. 31P magnetic resonance. J Biol Chem 248, 7276-7278.
57. Mourmans J, Wendel U, Bentlage HA, Trijbels JM, Smeitink JA, de Coo IF, Gabreels FJ, Sengers RC & Ruitenbeek W (1997). Clinical heterogeneity in respiratory chain complex III deficiency in childhood. J Neurol Sci 149, 111-117.
58. Nakashima T, Tomi M, Katayama K, Tachikawa M, Watanabe M, Terasaki T & Hosoya K (2004). Blood-to-retina transport of creatine via creatine transporter (CRT) at the rat inner blood-retinal barrier. J Neurochem 89, 1454-1461.
59. Nicolay K, van Dorsten FA, Reese T, Kruiskamp MJ, Gellerich JF & van Echteld CJ (1998). In situ measurements of creatine kinase flux by NMR. The lessons from bioengineered mice. Mol Cell Biochem 184, 195-208.
60. O'Connor RS, Steeds CM, Wiseman RW & Pavlath GK (2008). Phosphocreatine as an energy source for actin cytoskeletal rearrangements during myoblast fusion. J Physiol 586, 2841-2853.
61. O'Gorman E, Beutner G, Wallimann T & Brdiczka D (1996). Differential effects of creatine depletion on the regulation of enzyme activities and on creatine-stimulated mitochondrial respiration in skeletal muscle, heart, and brain. Biochim Biophys Acta 1276, 161-170.
62. O'Gorman E, Fuchs KH, Tittmann P, Gross H & Wallimann T (1997). Crystalline mitochondrial inclusion bodies isolated from creatine depleted rat soleus muscle. J Cell Sci 110, 1403-1411.
63. Ohtsuki S, Tachikawa M, Takanaga H, Shimizu H, Watanabe M, Hosoya K & Terasaki T (2002). The blood-brain barrier creatine transporter is a major pathway for supplying creatine to the brain. J Cereb Blood Flow Metab 22, 1327-1335.
64. Pathare N, Walter GA, Stevens JE, Yang Z, Okerke E, Gibbs JD, Esterhai JL, Scarborough MT, Gibbs CP, Sweeney HL & Vandenborne K (2005). Changes in inorganic phosphate and force production in human skeletal muscle after cast immobilization. J Appl Physiol 98, 307-314.
65. Perasso L, Cupello A, Lunardi GL, Principato C, Gandolfo C & Balestrino M (2003). Kinetics of creatine in blood and brain after intraperitoneal injection in the rat. Brain Res 974, 37-42.
66. 1H NMR spectra of the rat brain. J Magn Reson 141, 104-120.
67. Provencher SW (1993). Estimation of metabolite concentrations from localized in vivo proton NMR spectra. Magn Reson Med 30, 672-679.
68. Pyne-Geithman GJ, deGrauw TJ, Cecil KM, Chuck G, Lyons MA, Ishida Y & Clark JF (2004). Presence of normal creatine in the muscle of a patient with a mutation in the creatine transporter: a case study. Mol Cell Biochem 262, 35-39.
69. Ren JM, Semenkovich CF & Holloszy JO (1993). Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transporter expression. Am J Physiol 264, C146-C150.
70. Renema WK, Schmidt A, van Asten JJ, Oerlemans F, Ullrich K, Wieringa B, Isbrandt D & Heerschap A (2003). MR spectroscopy of muscle and brain in guanidinoacetate methyltransferase (GAMT)-deficient mice: validation of an animal model to study creatine deficiency. Magn Reson Med 50, 936-943.
71. Roberts JJ & Walker JB (1983). Synthesis and accumulation of an extremely stable high-energy phosphate compound by muscle, heart, and brain of animals fed the creatine analog, 1-carboxyethyl-2-iminoimidazolidine (homocyclocreatine). Arch Biochem Biophys 220, 563-571.
72. Roos A & Boron WF (1981). Intracellular pH. Physiol Rev 61, 296-434.
73. Saks V (2008). The phosphocreatine-creatine kinase system helps to shape muscle cells and keep them healthy and alive. J Physiol 586, 2817-2818.
74. Saks V, Kaambre T, Guzun R, Anmann T, Sikk P, Schlattner U, Wallimann T, Aliev M & Vendelin M (2007). The creatine kinase phosphotransfer network: thermodynamic and kinetic considerations, the impact of the mitochondrial outer membrane and modelling approaches. Subcell Biochem 46, 27-65.
75. Salomons G & Wyss M (2007). Creatine and creatine kinase in health and disease-a bright future ahead? Subcell Biochem 46, 309-334.
76. Scheibye-Knudsen M & Quistorff B (2009). Regulation of mitochondrial respiration by inorganic phosphate; comparing permeabilized muscle fibers and isolated mitochondria prepared from type-1 and type-2 rat skeletal muscle. Eur J Appl Physiol 105, 279-287.
77. Schmidt A, Marescau B, Boehm EA, Renema WK, Peco R, Das A, Steinfeld R, Chan S, Wallis J, Davidoff M, Ullrich K, Waldschutz R, Heerschap A, De Deyn PP, Neubauer S & Isbrandt D (2004). Severely altered guanidino compound levels, disturbed body weight homeostasis and impaired fertility in a mouse model of guanidinoacetate N-methyltransferase (GAMT) deficiency. Hum Mol Genet 13, 905-921.
78. Schulze A & Battini R (2007). Pre-symptomatic treatment of creatine biosynthesis defects. Subcell Biochem 46, 167-181.
79. Shoubridge EA, Challiss RA, Hayes DJ & Radda GK (1985). Biochemical adaptation in the skeletal muscle of rats depleted of creatine with the substrate analogue beta-guanidinopropionic acid. Biochem J 232, 125-131.
80. Sjøgaard G & Saltin B (1982). Extra- and intracellular water spaces in muscles of man at rest and with dynamic exercise. Am J Physiol 243, R271-R280.
81. Skelton MR, Schaefer TL, Graham DL, Degrauw TJ, Clark JF, Williams MT & Vorhees CV (2011). Creatine transporter (CrT; Slc6a8) knockout mice as a model of human CrT deficiency. PLoS One 6, e16187.
82. Sora I, Richman J, Santoro G, Wei H, Wang Y, Vanderah T, Horvath R, Nguyen M, Waite S, Roeske WR & Yamamura HI (1994). The cloning and expression of a human creatine transporter. Biochem Biophys Res Commun 204, 419-427.
83. Stadhouders AM, Jap PH, Winkler HP, Eppenberger HM & Wallimann T (1994). Mitochondrial creatine kinase: a major constituent of pathological inclusions seen in mitochondrial myopathies. Proc Natl Acad Sci U S A 91, 5089-5093.
84. 2+ responses in muscles with combined mitochondrial and cytosolic creatine kinase deficiencies. Cell 89, 93-103.
85. Steeghs K, Heerschap A, de Haan A, Ruitenbeek W, Oerlemans F, van Deursen J, Perryman B, Pette D, Brückwilder M, Koudijs J, Jap P & Wieringa B (1997b). Use of gene targeting for compromising energy homeostasis in neuro-muscular tissues: the role of sarcomeric mitochondrial creatine kinase. J Neurosci Methods 71, 29-41.
86. Steeghs K, Oerlemans F, de Haan A, Heerschap A, Verdoodt L, de Bie M, Ruitenbeek W, Benders A, Jost C, van Deursen J, Tullson P, Terjung R, Jap P, Jacob W, Pette D & Wieringa B (1998). Cytoarchitectural and metabolic adaptations in muscles with mitochondrial and cytosolic creatine kinase deficiencies. Mol Cell Biochem 184, 183-194.
87. Stöckler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M, Hänicke W & Frahm J (1994). Creatine deficiency in the brain: a new, treatable inborn error of metabolism. Pediatr Res 36, 409-413.
88. Stöckler S, Marescau B, De Deyn PP, Trijbels JM & Hanefeld F (1997). Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism 46, 1189-1193.
89. Tachikawa M, Fukaya M, Terasaki T, Ohtsuki S & Watanabe M (2004). Distinct cellular expressions of creatine synthetic enzyme GAMT and creatine kinases uCK-Mi and CK-B suggest a novel neuron-glial relationship for brain energy homeostasis. Eur J Neurosci 20, 144-160.
90. ten Hove M, Makinen K, Sebag-Montefiore L, Hunyor I, Fischer A, Wallis J, Isbrandt D, Lygate C & Neubauer S (2008). Creatine uptake in mouse hearts with genetically altered creatine levels. J Mol Cell Cardiol 45, 453-459.
91. 1H NMR spectroscopy of rat brain at 1 ms echo time. Magn Reson Med 41, 649-656.
92. van Loon LJ, Oosterlaar AM, Hartgens F, Hesselink MK, Snow RJ & Wagenmakers AJ (2003). Effects of creatine loading and prolonged creatine supplementation on body composition, fuel selection, sprint and endurance performance in humans. Clin Sci (Lond) 104, 153-162.
93. Walker JB (1979). Creatine: biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 50, 177-242.
94. Wilkinson ID, Mitchel N, Breivik S, Greenwood P, Griffiths PD, Winter EM & Van Beek EJ (2006). Effects of creatine supplementation on cerebral white matter in competitive sportsmen. Clin J Sport Med 16, 63-67.
95. Winder WW, Holmes BF, Rubink DS, Jensen EB, Chen M & Holloszy JO (2000). Activation of AMP-activated protein kinase increases mitochondrial enzymes in skeletal muscle. J Appl Physiol 88, 2219-2226.
96. Wyss M & Kaddurah-Daouk R (2000). Creatine and creatinine metabolism. Physiol Rev 80, 1107-1213.
97. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ & Shulman GI (2002). AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci U S A 99, 15983-15987.