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Creatine metabolism and the consequences of creatine depletion in muscle

  • Muscle Energy Metabolism
  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Currently, considerable research activities are focussing on biochemical, physiological and pathological aspects of the creatine kinase (CK) — phosphorylcreatine (PCr) — creatine (Cr) system (for reviews see [1, 2]), but only little effort is directed towards a thorough investigation of Cr metabolism as a whole. However, a detailed knowledge of Cr metabolism is essential for a deeper understanding of bioenergetics in general and, for example, of the effects of muscular dystrophies, atrophies, CK deficiencies (e.g. in transgenic animals) or Cr analogues on the energy metabolism of the tissues involved. Therefore, the present article provides a short overview on the reactions and enzymes involved in Cr biosynthesis and degradation, on the organization and regulation of Cr metabolism within the body, as well as on the metabolic consequences of 3-guanidinopropionate (GPA) feeding which is known to induce a Cr deficiency in muscle. In addition, the phenotype of muscles depleted of Cr and PCr by GPA feeding is put into context with recent investigations on the muscle phenotype of ‘gene knockout’ mice deficient in the cytosolic muscle-type M-CK.

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Abbreviations

Cr:

creatine

Crn:

creatinine

PCr:

phosphorylcreatine

CK:

creatine kinase

M-CK:

cytosolic muscle type CK isoenzyme

Mi-CK:

mitochondrial CK isoenzyme

AGAT:

L-arginine: glycine amidinotransferase

GAMT:

S-adenosylmethionine: guanidinoacetate methyltransferase

Arg:

arginine

Met:

methionine

GPA:

guanidinopropionate=β-guanidinopropionate

PGPA:

phosphorylated GPA

GBA:

3-guanidinobutyrate=β-guanidinobutyrate

CPEO:

chronic progressive external ophthalmoplegia

References

  1. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Significance of intracellular compartmentation, structure and function of creatine kinase isoenzymes for cellular energy homeostasis: ‘The Phospho-Creatine Circuit’. Biochem J 281: 21–40, 1992

    Google Scholar 

  2. Wyss M, Smeitink J, Wevers RA, Wallimann T: Mitochondrial creatine kinase: a key enzyme of aerobic energy metabolism. Biochim Biophys Acta 1102: 119–166, 1992

    PubMed  Google Scholar 

  3. Bloch K, Schoenheimer R: The biological formation of creatine. J Biol Chem 133: 633–634, 1940

    Google Scholar 

  4. Bloch K, Schoenheimer R: The biological origin of the amidine group in creatine. J Biol Chem 134: 785–786, 1940

    Google Scholar 

  5. van Pilsum JF, Stephens GC, Taylor D: Distribution of creatine, guanidinoacetate and the enzymes for their biosynthesis in the animal kingdom. Biochem J 126: 325–345, 1972

    Google Scholar 

  6. Needham DM, Needham J, Baldwin E, Yudkin J: A comparative study of the phosphagens, with some remarks on the origin of vertebrates. Nature 110: 260–294, 1932

    Google Scholar 

  7. Ennor AH, Morrison JF: Biochemistry of the phosphagens and related guanidines. Physiol Rev 38: 631–674, 1958

    PubMed  Google Scholar 

  8. Robin Y: Biological distribution of guanidines and phosphagens in marine annelida and related phyla from california, with a note on pluriphosphagens. Comp Biochem Physiol 12: 347–367, 1964

    Google Scholar 

  9. Watts DC: Evolution of phosphagen kinases. In: E. Schoffeniels (ed). Biochemical Evolution and the Origin of Life, North-Holland Publishing Company, 1971, pp 150–173

  10. Walker JB: Creatine: biosynthesis, regulation, and function. Adv Enzymol 50: 177–242 1979

    PubMed  Google Scholar 

  11. Horner WH: Transamidination in the nephrectomized rat. J Biol Chem 234: 2386–2387, 1959

    PubMed  Google Scholar 

  12. Fitch CD, Hsu C, Dinning JS: The mechanism of kidney transamidinase reduction in vitamin E-deficient rabbits. J Biol Chem 236: 490–492, 1961

    PubMed  Google Scholar 

  13. McGuire DM, Gross MD, Elde RP, van Pilsum JF: Localization of L-arginine-glycine amidinotransferase protein in rat tissues by immunofluorescence microscopy. J Histochem Cytochem 34: 429–435, 1986

    PubMed  Google Scholar 

  14. van Pilsum JF, Olsen B, Taylor D, Rozycki T, Pierce JC: Transamidinase activities,in vitro, of tissues from various mammals and from rats fed protein-free, creatine-supplemented and normal diets. Arch Biochem Biophys 100: 520–524, 1963

    PubMed  Google Scholar 

  15. Yanokura M, Tsukada K: Decreased activities of glycine and guanidinoacetate methyltransferases and increased levels of creatine in tumor cells. Biochem Biophys Res Commun 104: 1464–1469, 1982

    PubMed  Google Scholar 

  16. Daly MM: Guanidinoacetate methyltransferase activity in tissues and cultured cells. Arch Biochem Biophys 236: 576–584, 1985

    PubMed  Google Scholar 

  17. Holtzman D, McFarland E, Moerland T, Koutcher J, Kusimerick MJ, Neuringer LJ: Brain creatine phosphate and creatine kinase in mice fed an analogue of creatine. Brain Res 483: 68–77, 1989

    PubMed  Google Scholar 

  18. Defalco AJ, Davies RK: The synthesis of creatine by the brain of the intact rat. J Neurochem 7: 308–312, 1961

    PubMed  Google Scholar 

  19. Fitch CD, Shields RP: Creatine metabolism in skeletal muscle. I. Creatine movement across muscle membranes. J Biol Chem 241: 3611–3614, 1966

    PubMed  Google Scholar 

  20. Seraydarian MW, Artaza L, Abbott BC: Creatine and the control of energy metabolism in cardiac and skeletal muscle cells in culture. J Mol Cell Cardiol 6: 405–413, 1974

    PubMed  Google Scholar 

  21. Syllm-Rapoport I, Daniel A, Rapoport S: Creatine transport into red blood cells. Acta Biol Med Germ 39: 771–779, 1980

    PubMed  Google Scholar 

  22. Syllm-Rapoport I, Daniel A, Starck H, Götze W, Hartwig A, Gross J, Rapoport S: Creatine in red cells: transport and erythropoietic dynamics. Acta Biol Med Germ 40: 653–659, 1981

    PubMed  Google Scholar 

  23. Daly MM, Seifter S: Uptake of creatine by cultured cells. Arch Biochem Biophys 203: 317–324, 1980

    PubMed  Google Scholar 

  24. Ku C-P, Passow H: Creatine and creatinine transport in old and young human red blood cells. Biochim Biophys Acta 600: 212–227, 1980

    PubMed  Google Scholar 

  25. Loike JD, Somes M, Silverstein SC: Creatine uptake, metabolism, and efflux in human monocytes and macrophages. Am J Physiol 251: C128-C135, 1986

    PubMed  Google Scholar 

  26. Möller A, Hamprecht B: Creatine transport in cultured cells of rat and mouse brain. J Neurochem 52: 544–550, 1989

    PubMed  Google Scholar 

  27. Guimbal C, Kilimann MW: A Na+-dependent creatine transporter in rabbit brain, muscle, heart and kidney. cDNA cloning and functional expression. J Biol Chem 268: 8418–8421, 1993

    PubMed  Google Scholar 

  28. Baker Z, Miller BF: Studies on the metabolism of creatine and creatinine. II. The distribution of creatine and creatinine in the tissues of the rat, dog, and monkey. J Biol Chem 130: 393–397, 1939

    Google Scholar 

  29. Peters JP, van Slyke DD: Quantitative Clinical Chemistry, Interpretations, Vol I, 2nd ed, Williams & Wilkins Co, Baltimore, 1946

    Google Scholar 

  30. Berlet HH, Bonsmann I, Birringer H: Occurrence of free creatine, phosphocreatine and creatine phosphokinase in adipose tissue. Biochim Biophys Acta 437: 166–174, 1976

    PubMed  Google Scholar 

  31. Wallimann T, Eppenberger HM: Localization and function of M-line-bound creatine kinase. M-band model and creatine phosphate shuttle. In: J.W. Shay (ed). Cell and Muscle Motility, Vol 6, Plenum Publishing Corp, 1985, pp 239–285

  32. Wallimann T, Moser H, Zurbriggen B, Wegmann G, Eppenberger HM: Creatine kinase isoenzymes in spermatozoa. J Muscle Res Cell Motil 7: 25–34, 1986

    PubMed  Google Scholar 

  33. Wallimann T, Wegmann G, Moser H, Huber R, Eppenberger HM: High content of creatine kinase in chicken retina: compartmentalized localization of creatine kinase isoenzymes in photoreceptor cells. Proc Natl Acad Sci USA 83: 3816–3819, 1986

    PubMed  Google Scholar 

  34. Lee HJ, Fillers WS, Iyengar MR: Phosphocreatine, an intracellular high-energy compound, is found in the extracellular fluid of the seminal vesicles in mice and rats. Proc Natl Acad Sci USA 85: 7265–7269, 1988

    PubMed  Google Scholar 

  35. Delanghe J, De Slypere J-P, De Buyzere M, Robbrecht J, Wieme R, Vermeulen A: Normal reference values for creatine, creatinine, and carnitine are lower in vegetarians. Clin Chem 35: 1802–1803, 1989

    PubMed  Google Scholar 

  36. Kushmerick MJ, Moerland TS, Wiseman RW: Mammalian skeletal muscle fibers distinguished by contents of phosphocreatine, ATP and Pi. Proc Natl Acad Sci USA 89: 7521–7525, 1992

    PubMed  Google Scholar 

  37. Harris RC, Hultman E: Muscle phosphagen status studied by needle biopsy. In: J.M. Kinney and H.N. Tucker (eds). Energy Metabolism: Tissue Determinants and Cellular Corollaries. Raven Press, NY, 1992, pp 367–379

    Google Scholar 

  38. Edgar G, Shiver HE: The equilibrium between creatine and creatinine, in aqueous solution. The effect of hydrogen ion. J Am Chem Soc 47: 1179–1188, 1925

    Google Scholar 

  39. Cannan RK, Shore A: The creatine-creatinine equilibrium. The apparent dissociation constants of creatine and creatinine. Biochem J 22: 920–929, 1928

    Google Scholar 

  40. Morrison JF, Ennor AH: N-Phosphorylated guanidines. In: P.D. Boyer, H. Lardy, and K. Myrbäck (eds). The Enzymes, 2nd ed, Vol 2, Academic Press, NY, 1960, pp 89–109

    Google Scholar 

  41. Bloch K, Schoenheimer R: Studies in protein metabolism. XI. The metabolic relation of creatine and creatinine studied with isotopic nitrogen. J Biol Chem 131: 111–119, 1939

    Google Scholar 

  42. Crim MC, Calloway DH, Margen S: Creatine metabolism in men: creatine pool size and turnover in relation to creatine intake. J Nutr 106: 371–381, 1976

    Google Scholar 

  43. van Hoogenhuyze CJC, Verploegh H: Beobachtungen über die Kreatininausscheidung beim Menschen. Zschr physiol Chem 46: 415–471, 1905

    Google Scholar 

  44. Iyengar MR, Coleman DW, Butler TM: Phosphocreatinine, a high-energy phosphate in muscle, spontaneously forms phosphocreatine and creatinine under physiological conditions. J Biol Chem 260: 7562–7567, 1985

    PubMed  Google Scholar 

  45. Clark VM, Warren SG: Why do phosphagens function as phosphoryl-transfer reagents? Nature 199: 657–659, 1963

    PubMed  Google Scholar 

  46. Akamatsu S, Kanai Y: Bacterial decomposition of creatinine. I. Creatinomutase. Enzymologia 15: 122–125, 1951

    PubMed  Google Scholar 

  47. Akamatsu S, Miyashita R: Bacterial decomposition of creatine. III. The pathway of creatine decomposition. Enzymologia 15: 173–176, 1951

    Google Scholar 

  48. Szulmajster J: Bacterial fermentation of creatinine. I. Isolation of N-methyl-hydantoin. J Bacteriol 75: 633–639, 1958

    PubMed  Google Scholar 

  49. Szulmajster J: Bacterial degradation of creatinine. II. Creatinine desimidase. Biochim Biophys Acta 30: 154–163, 1958

    PubMed  Google Scholar 

  50. van Eyk HG, Vermaat RJ, Leijnse-Ybema HJ, Leijnse B: The conversion of creatinine by creatininase of bacterial origin. Enzymologia 34: 198–202, 1968

    PubMed  Google Scholar 

  51. Forde A, Johnson DB: Preliminary studies on enzymes of creatinine degradation. Biochem Soc Trans 2: 1342–1344, 1974

    Google Scholar 

  52. Chang MC, Chang CC, Chang JC: Cloning of a creatinase gene fromPseudomonas putida inEscherichia coli by using an indicator plate. Appl Environm Microbiol 58: 3437–3440, 1992

    Google Scholar 

  53. Miyoshi K, Taira A, Yoshida K, Tamura K, Uga S: Presence of creatinase and sarcosine dehydrogenase in human skeletal muscle. Proposal for creatine-urea pathway. Proc Japan Acad 56B: 95–98, 1980

    Google Scholar 

  54. Miyoshi K, Taira A, Yoshida K, Tamura K, Uga S: Abnormalities of creatinase in skeletal muscle of patients with Duchenne muscular dystrophy. Proc Japan Acad 56B: 99–101, 1980

    Google Scholar 

  55. Mudd SH, Ebert MH, Scriver CR: Labile methyl group balances in the human: the role of sarcosine. Metabolism 29: 707–720, 1980

    PubMed  Google Scholar 

  56. McGuire DM, Gross MD, van Pilsum JF, Towle HC: Repression of rat kidney L-arginine: glycine amidinotransferase synthesis by creatine at a pretranslational level. J Biol Chem 259: 12034–12038, 1984

    PubMed  Google Scholar 

  57. van Pilsum JF, McGuire DM, Miller CA: The antagonistic action of creatine and growth hormone on the expression of the gene for rat kidney L-arginine: glycine amidinotransferase. In: P.P. De Deyn, B. Marescau, V. Stalon and I.A. Qureshi (eds). Guanidino Compounds in Biology and Medicine, John Libbey & Company Ltd, 1992, pp 147–151

  58. Walker JB, Wang S-H: Tissue repressor concentration and target enzyme level. Biochim Biophys Acta 81: 435–441, 1964

    PubMed  Google Scholar 

  59. Roberts JJ, Walker JB: Higher homolog and N-ethyl analog of creatine as synthetic phosphagen precursors in brain, heart, and muscle, repressors of liver amidinotransferase, and substrates for creatine catabolic enzymes. J Biol Chem 260: 13502–13508, 1985

    PubMed  Google Scholar 

  60. Gross MD, Simon AM, Jenny RJ, Gray ED, McGuire DM, van Pilsum JF: Multiple forms of rat kidney L-arginine: glycine amidinotransferase. J Nutr 118: 1403–1409, 1988

    PubMed  Google Scholar 

  61. Methfessel J: Transamidinase. Zschr inn Med 25: 80–84, 1970

    Google Scholar 

  62. van Pilsum JF, Wahman RE: Creatine and creatinine in the carcass and urine of normal and vitamin E-deficient rabbits. J Biol Chem 235: 2092–2094, 1960

    PubMed  Google Scholar 

  63. Funahashi M, Kato H, Shiosaka S, Nakagawa H: Formation of arginine and guanidinoacetic acid in the kidneyin vivo. Their relations with the liver and their regulation. J Biochem 89: 1347–1356, 1981

    PubMed  Google Scholar 

  64. van Pilsum JF, Carlson M, Boen JR, Taylor D, Zakis B: A bioassay for thyroxine based on rat kidney transamidinase activities. Endocrinology 87: 1237–1244, 1970

    PubMed  Google Scholar 

  65. McGuire DM, Tormanen CD, Segal IS, van Pilsum JF: The effect of growth hormone and thyroxine on the amount of L-arginine: glycine amidinotransferase in kidneys of hypophysectomized rats. Purification and some properties of rat kidney transamidinase. J Biol Chem 255: 1152–1159, 1980

    PubMed  Google Scholar 

  66. Sipilä I: Inhibition of arginine-glycine amidinotransferase by ornithine. A possible mechanism for the muscular and chorioretinal atrophies in gyrate atrophy of the choroid and retina with hyperornithinemia. Biochim Biophys Acta 613: 79–84, 1980

    PubMed  Google Scholar 

  67. Valle D, Kaiser-Kupfer MI, Del Valle LA: Gyrate atrophy of the choroid and retina: deficiency of ornithine aminotransferase in transformed lymphocytes. Proc Natl Acad Sci USA 74: 5159–5161, 1977

    PubMed  Google Scholar 

  68. Grazi E, Magri E, Balboni G: On the control of arginine metabolism in chicken kidney and liver. Eur J Biochem 60: 431–436, 1975

    PubMed  Google Scholar 

  69. Loike JD, Zalutsky DL, Kaback E, Miranda AF, Silverstein SC: Extracellular creatine regulates creatine transport in rat and human muscle cells. Proc Natl Acad Sci USA 85: 807–811, 1988

    PubMed  Google Scholar 

  70. Gellerich FN, Schlame M, Bohnensack R, Kunz W: Dynamic compartmentation of adenine nucleotides in the mitochondrial intermembrane space of rat-heart mitochondria. Biochim Biophys Acta 890: 117–126, 1987

    PubMed  Google Scholar 

  71. Gellerich FN, Khuchua ZA, Kuznetsov AV: Influence of the mitochondrial outer membrane and the binding of creatine kinase to the mitochondrial inner membrane on the compartmentation of adenine nucleotides in the intermembrane space of rat heart mitochondria. Biochim Biophys Acta 1140: 327–334, 1993

    PubMed  Google Scholar 

  72. Brdiczka D: Contact sites between mitochondrial envelope membranes. Structure and function in energy- and protein-transfer. Biochim Biophys Acta 1071: 291–312, 1991

    PubMed  Google Scholar 

  73. Liu M, Colombini M: Voltage gating of the mitochondrial outer membrane channel VDAC is regulated by a very conserved protein. Am J Physiol 260: C371-C374, 1991

    PubMed  Google Scholar 

  74. Seppet EK, Adoyaan AJ, Kallikorm AP, Chernousova GB, Lyulina NV, Sharov VG, Severin VV, Popovich MI, Saks VA: Hormone regulation of cardiac energy metabolism. I. Creatine transport across cell membranes of euthyroid and hyperthyroid rat heart. Biochem Med 34: 267–279, 1985

    PubMed  Google Scholar 

  75. Ingwall JS, Atkinson DE, Clarke K, Fetters JK: Energetic correlates of cardiac failure: changes in the creatine kinase system in the failing myocard. Eur Heart J. 11 (Suppl B), 108–115, 1990

    Google Scholar 

  76. Ingwall JS, Kramer MF, Fifer MA, Lovell BH, Shemin R, Grossman W, Allen PD: The creatine kinase system in normal and diseased human myocardium. N Engl J Med 131: 1050–1054, 1985

    Google Scholar 

  77. Fitch CD: Significance of abnormalities of creatine metabolism. In: P. Rowland (ed), Pathogenesis of human muscular dystrophies. Excerpta Medica, Amsterdam, 1977, pp 328–336

    Google Scholar 

  78. Fitch CD, Jellinek M, Mueller E: Experimental depletion of creatine and phosphocreatine from skeletal muscle. J Biol Chem 249: 1060–1063, 1974

    PubMed  Google Scholar 

  79. Fitch CD, Chevli R: Inhibition of creatine and phosphocreatine accumulation in skeletal muscle and heart. Metabolism 29: 686–690, 1980

    PubMed  Google Scholar 

  80. Shoubridge EA, Radda GK: A31P nuclear magnetic resonance study of skeletal muscle metabolism in rats depleted of creatine with the analogue β-guanidino-propionic acid. Biochim Biophys Acta 805: 79–88, 1984

    PubMed  Google Scholar 

  81. Shoubridge EA, Radda GK: A gated31P NMR study of tetanic contraction in rat muscle depleted of phosphocreatine. Am J Physiol 252: C532-C542, 1987

    PubMed  Google Scholar 

  82. Meyer RA, Brown TR, Krilowicz BL, Kushmerick MJ: Phosphagen and intracellular pH changes during contraction of creatine-depleted muscle. Am J Physiol 250: C264-C274, 1986

    PubMed  Google Scholar 

  83. Mekhfi H, Hoerter J, Lauer C, Wisnewsky C, Schwartz K, Ventura-Clapier R: Myocardial adaptation to creatine deficiency in rats fed with β-guanidinopropionic acid, a creatine analogue. Am J Physiol 258: H1151-H1158, 1990

    PubMed  Google Scholar 

  84. Zweier JL, Jacobus WE, Korecky B, Brandejs-Barry Y: Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding. J Biol Chem 266: 20296–20304, 1991

    PubMed  Google Scholar 

  85. Shoubridge EA, Jeffry FMH, Keogh JM, Radda GK, Seymour A-ML: Creatine kinase kinetics, ATP turnover, and cardiac performance in hearts depleted of creatine with the substrate analogue β-guanidinopropionic acid. Biochim Biophys Acta 847: 25–32, 1985

    PubMed  Google Scholar 

  86. Conley KE, Kushmerick MJ: Buffering work transitions in myocardium: role of a poorly metabolized creatine analogue. Magn Res Med 2: 902, 1990

    Google Scholar 

  87. Fitch CD, Jellinek M, Fitts RH, Baldwin KM, Holloszy JO: Phosphorylated β-guanidinopropionate as a substitute for phosphocreatine in rat muscle. Am J Physiol 228: 1123–1125, 1975

    PubMed  Google Scholar 

  88. Chevli R, Fitch CD: beta-Guanidinopropionate and phosphorylated beta-guanidinopropionate as substrates for creatine kinase. Biochem Med 21: 162–167, 1979

    PubMed  Google Scholar 

  89. Mainwood GW, Alward M, Eiselt B: Contractile characteristics of creatine-depleted rat diaphragm. Can J Physiol Pharmacol 60: 120–127, 1982

    PubMed  Google Scholar 

  90. Mainwood GW, Alward M, Eiselt B: The effects of metabolic inhibition on the contraction of creatine-depleted muscle. Can J Physiol Pharmacol 60: 114–119, 1982

    PubMed  Google Scholar 

  91. Mainwood GW, de Zepetnek JT: Post-tetanic responses in creatine-depleted rat EDL. Muscle Nerve 8: 774–782, 1985

    PubMed  Google Scholar 

  92. Petrofsky JS, Fitch CD: Contractile characteristics of skeletal muscle depleted of phosphocreatine. Pflügers Arch 384: 123–129, 1980

    Google Scholar 

  93. Korecky B, Brandejs-Barry Y: Effect of creatine depletion on myocardial mechanics. Basic Res Cardiol 82 (Suppl 2): 103–110, 1987

    PubMed  Google Scholar 

  94. Kapelko VI, Kupriyanov VV, Novikova NA, Lakomkin VL, Steinschneider AYa, Severina MYu, Veksler VI, Saks VA: The cardiac contractility failure induced by chronic creatine and phosphocreatine deficiency. J Mol Cell Cardiol 20: 465–479, 1988

    PubMed  Google Scholar 

  95. Otten JV, Fitch CD, Wheatley JB, Fischer VW: Thyrotoxic myopathy in mice: accentuation by a creatine transport inhibitor. Metabolism 35: 481–484, 1986

    PubMed  Google Scholar 

  96. Hasselbach W, Oetliker H: Energetics and electrogenicity of the sarcoplasmic reticulum pump. Annu Rev Physiol 45: 325–339, 1983

    PubMed  Google Scholar 

  97. Kammermeier H: Why do cells need phospho-creatine and a phospho-creatine shuttle. J Mol Cell Cardiol 19: 115–118, 1987

    PubMed  Google Scholar 

  98. Rossi AM, Eppenberger HM, Volpe P, Cotrufo R, Wallimann T: Muscle-type MM-creatine kinase is specifically bound to sarcoplasmic reticulum and can support Ca2+-uptake and regulate local ATP/ADP ratios. J Biol Chem 265: 5258–5266, 1990

    PubMed  Google Scholar 

  99. Korge P, Byrd SK, Campbell KB: Functional coupling between sarcoplasmic-reticulum-bound creatine kinase and Ca2+-ATPase. Eur J Biochem 213: 973–980, 1993

    PubMed  Google Scholar 

  100. Pette D: Plasticity of Muscle. Walter de Gruyter, Berlin and New York, 1980

    Google Scholar 

  101. Pette D: The Dynamic State of Muscle Fibers. Walter de Gruyter, Berlin and New York, 1990

    Google Scholar 

  102. Shoubridge EA, Challiss JRA, Hayes DJ, Radda GK: Biochemical adaptation in the skeletal muscle of rats depleted of creatine with the substrate analogue β-guanidinopropionic acid. Biochem J 232: 125–131, 1985

    PubMed  Google Scholar 

  103. Lai MM, Booth FW: Cytochrome c mRNA and α-actin mRNA in muscles of rats fed β-GPA. J Appl Physiol 69: 843–848, 1990

    PubMed  Google Scholar 

  104. Ren JM, Semenkovich CF, Holloszy JO: Adaptation of muscle to creatine depletion: effect on GLUT-4 glucose transport expression. Am J Physiol 264: C146-C150, 1993

    PubMed  Google Scholar 

  105. Moerland TS, Wolf NG, Kushmerick MJ: Administration of a creatine analogue induces isomyosin transitions in muscle. Am J Physiol 257: C810-C816, 1989

    PubMed  Google Scholar 

  106. Ren JM, Holloszy JO: Adaptation of rat skeletal muscle to creatine depletion: AMP deaminase and AMP deamination. J Appl Physiol 73: 2713–2716, 1992

    PubMed  Google Scholar 

  107. Unitt JF, Radda GK, Seymour AM: The acute effects of the creatine analogue, β-guanidinopropionic acid, on cardiac energy metabolism and function. Biochim Biophys Acta 1143: 91–96, 1993

    PubMed  Google Scholar 

  108. Young RB, Denome RM: Effect of creatine on contents of myosin heavy chain and myosin-heavy-chain mRNA in steady-state chicken muscle-cell cultures. Biochem J 218: 871–876, 1984

    PubMed  Google Scholar 

  109. Eppenberger-Eberhardt M, Riesinger I, Messerli M, Schwarb P, Müller M, Eppenberger HM, Wallimann T: Adult rat cardiomyocytes cultured in creatine-deficient medium display large mitochondria with paracrystalline inclusions enriched for creatine kinase. J Cell Biol 113: 289–302, 1991

    PubMed  Google Scholar 

  110. Ohira Y, Kanzaki M, Chen CS: Intramitochondrial inclusions caused by depletion of creatine in rat skeletal muscles. Jap J Physiol 38: 159–166, 1988

    PubMed  Google Scholar 

  111. Gori Z, De Tata V, Pollera M, Bergamini E: Mitochondrial myopathy in rats fed with a diet containing beta-guanidine propionic acid, an inhibitor of creatine entry in muscle cells. Br J exp Pathol 69: 639–650, 1988

    PubMed  Google Scholar 

  112. De Tata V, Cavallini G, Pollera M, Gori Z, Bergamini E: The induction of mitochondrial myopathy in the rat by feeding β-guanidinopropionic acid and the reversibility of the induced mitochondrial lesions: a biochemical and ultrastructural investigation. Int J Exp Pathol 74: 501–509, 1993

    PubMed  Google Scholar 

  113. Pinson A, Schlüter KD, Zhou XJ, Schwartz P, Kessler-Icekson G, Piper HM: Alpha- and beta-adrenergic stimulation of protein synthesis in cultured adult ventricular cardiomyocytes. J Mol Cell Cardiol 25: 477–490, 1993

    PubMed  Google Scholar 

  114. Hanzlikova V, Schiaffino S: Mitochondrial changes in ischemic skeletal muscle. J Ultrastruct Res 60: 121–133, 1979

    Google Scholar 

  115. Heine H, Schaeg G: Origin and function of ‘rod-like structures’ in mitochondria. Acta anat 103: 1–10, 1979

    PubMed  Google Scholar 

  116. Melmed C, Karpati G, Carpenter S: Experimental mitochondrial myopathy produced byin vivo uncoupling of oxidative phosphorylation. J Neurol Sci 26: 305–318, 1975

    PubMed  Google Scholar 

  117. Riesinger I, Haas C, Wallimann T: Mitochondrial inclusions induced by feeding a creatine analogue exhibit a high density of mitochondrial creatine kinase. EBEC Short Reports (Biochim Biophys Acta) 7: 140 1992

    Google Scholar 

  118. Hall JD, Crane FL: A new structure in beef heart mitochondria. J Cell Biol 48: 420–425, 1971

    Google Scholar 

  119. Rojo M, Hovius R, Nicolay K, Wallimann T: Mitochondrial creatine kinase mediates contact formation between mitochondrial membranes. J Biol Chem 266: 20290–20295, 1991

    PubMed  Google Scholar 

  120. Schnyder T, Winkler H, Gross H, Eppenberger HM, Wallimann T: Structure of the mitochondrial creatine kinase octamer: High resolution shadowing and image averaging of single molecules and formation of linear filaments under specific staining conditions. J Cell Biol 112: 95–101, 1991

    PubMed  Google Scholar 

  121. Zeviani M, Bonilla E, DeVivo DC, DiMauro S: Mitochondrial Diseases. Neurol Clin 7: 123–156, 1989

    PubMed  Google Scholar 

  122. Harding, AE: Neurological disease and mitochondrial genes. TINS 14: 132–138, 1991

    PubMed  Google Scholar 

  123. Wallace, DC: Diseases of the mitochondrial DNA. Annu Rev Biochem 61: 1175–1212, 1992

    PubMed  Google Scholar 

  124. Wallace DC: Mitochondrial diseases: genotype versus phenotype. TIG 9: 128–133, 1993

    PubMed  Google Scholar 

  125. DiMauro S, Bonilla E, Zeviani M, Nakagawa M, DeVivo DC: Mitochondrial myopathies. Ann Neurol 17: 521–538, 1985

    PubMed  Google Scholar 

  126. Morgan-Hughes JA, Ayes DJ, Cooper M, Clark JB: Mitochondrial myopathies: Deficiencies localized to complex I and II of the respiratory chain. Biochem Soc Trans 13: 648–650, 1985

    PubMed  Google Scholar 

  127. Stadhouders AM: Mitochondrial ultrastructural changes in muscular diseases. In: H.F.M. Busch, F.G.I. Jennekens and H.R. Scholte (eds). Mitochondria and Muscular Diseases. Mefar b.v. Beetsterzwaag, The Netherlands, 1981, pp 113–132

    Google Scholar 

  128. Sarnat HB: Muscle pathology and histochemistry. Am Soc Clin Pathol Press, 1983, Chicago, USA

    Google Scholar 

  129. Schmalbruch H: The fine structure of mitochondrial abnormalities in muscle diseases. In: G. Scarlato and C. Cerri (eds). Mitochondrial Pathology in Muscle Diseases. Piccin Medical Books, Padua, Italy, 1983, pp 40–56

    Google Scholar 

  130. Farrants GW, Hovmöller S, Stadhouders AM: Two types of mitochondrial crystals in diseased human skeletal muscle fibers. Muscle Nerve 11: 45–55, 1988

    PubMed  Google Scholar 

  131. Stadhouders AM, Jap PHK, Winkler HP, Eppenberger HM, Wallimann T: Mitochondrial creatine kinase: a major constituent of pathological inclusions seen in mitochondrial myopathies. Proc Natl Acad Sci USA (in press), 1994

  132. Smeitink J, Stadhouders A, Sengers R, Ruitenbeek W, Wevers R, ter Laak H, Trijbels F: Mitochondrial creatine kinase containing crystals, creatine content and mitochondrial creatine kinase activity in chronic progressive external ophthalmoplegia. Neuromusc Disord 2: 35–40, 1992

    PubMed  Google Scholar 

  133. Heddi A, Lestienne P, Wallace DC, Stepien G: Mitochondrial DNA expression in mitochondrial myopathies and coordinated expression of nuclear genes involved in ATP production. J Biol Chem 268: 12156–12163 1993

    PubMed  Google Scholar 

  134. Wyss M, Wallimann T: Metabolite channelling in aerobic energy metabolism. J Theor Biol 158: 129–132, 1992

    PubMed  Google Scholar 

  135. Wallimann T: Dissection of the role of creatine kinase. The phenotype of gene ‘knock out’ mice deficient in a creatine kinase isoform sheds new light on the physiological function of the phosphocreatine circuit. Current Biol 4, 42–46: 1994

    Google Scholar 

  136. van Deursen J, Heerschap A, Oerlemans F, Ruitenbeek W, Jap P, ter Laak H, Wieringa B: Skeletal muscle of mice deficient in muscle creatine kinase lack burst activity. Cell 74: 621–631, 1993

    PubMed  Google Scholar 

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  1. Markus Wyss

    Present address: Department of Transplant Surgery, Research Division, University Hospital, Anichstr. 35, A-6020, Innsbruck, Austria

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  1. Swiss Federal Institute of Technology, Institute for Cell Biology, ETH Hönggerberg, CH-8093, Zürich, Switzerland

    Markus Wyss & Theo Wallimann

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  1. Markus Wyss
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Wyss, M., Wallimann, T. Creatine metabolism and the consequences of creatine depletion in muscle. Mol Cell Biochem 133, 51–66 (1994). https://doi.org/10.1007/BF01267947

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