Skip to main content
SpringerLink
Log in

Creatine transporters: A reappraisal

  • Published:
Molecular and Cellular Biochemistry Aims and scope Submit manuscript

Abstract

Creatine (Cr) plays a key role in cellular energy metabolism and is found at high concentrations in metabolically active cells such as skeletal muscle and neurons. These, and a variety of other cells, take up Cr from the extra cellular fluid by a high affinity Na+/Cl−-dependent creatine transporter (CrT). Mutations in the crt gene, found in several patients, lead to severe retardation of speech and mental development, accompanied by the absence of Cr in the brain.

In order to characterize CrT protein(s) on a biochemical level, antibodies were raised against synthetic peptides derived from the N- and C-terminal cDNA sequences of the putative CrT-1 protein. In total homogenates of various tissues, both antibodies, directed against these different epitopes, recognize the same two major polypetides on Western blots with apparent Mr of 70 and 55 kDa. The C-terminal CrT antibody (α-CrTCOOH) immunologically reacts with proteins located at the inner membrane of mitochondria as determined by immuno-electron microscopy, as well as by subfractionation of mitochondria. Cr-uptake experiments with isolated mitochondria showed these organelles were able to transport Cr via a sulfhydryl-reagent-sensitive transporter that could be blocked by anti-CrT antibodies when the outer mitochondrial membrane was permeabilized. We concluded that mitochondria are able to specifically take-up Cr from the cytosol, via a low-affinity CrT, and that the above polypeptides would likely represent mitochondrial CrT(s). However, by mass spectrometry techniques, the immunologically reactive proteins, detected by our anti-CrT antibodies, were identified as E2 components of the α-keto acid dehydrogenase multi enzyme complexes, namely pyruvate dehydrogenase (PDH), branched chain keto acid dehydrogenase (BC-KADH) and α-ketoglutarate dehydrogenase (α-KGDH). The E2 components of PDH are membrane associated, whilst it would be expected that a mitochondrial CrT would be a transmembrane protein. Results of phase partitioning by Triton X-114, as well as washing of mitochondrial membranes at basic pH, support that these immunologically cross-reactive proteins are, as expected for E2 components, membrane associated rather than transmembrane. On the other hand, the fact that mitochondrial Cr uptake into intact mitoplast could be blocked by our α-CrTCOOH antibodies, indicate that our antisera contain antibodies reactive to proteins involved in mitochondrial transport of Cr. The presence of specific antibodies against CrT is also supported by results from plasma membrane vesicles isolated from human and rat skeletal muscle, where both 55 and 70 kDa polypeptides disappeared and a single polypeptide with an apparent electrophoretic mobility of ~ 60 kDa was enriched This latter is most likely representing the genuine plasma membrane CrT.

Due to the fact that all anti-CrT antibodies that were independently prepared by several laboratories seem to cross-react with non-CrT polypeptides, specifically with E2 components of mitochondrial dehydrogenases, further research is required to characterise on a biochemical/biophysical level the CrT polypeptides, e.g. to determine whether the ~ 60 kDa polypeptide is indeed a bona-fide CrT and to identify the mitochondrial transporter that is able to facilitate Cr-uptake into these organelles. Therefore, the anti-CrT antibodies available so far should only be used with these precautions in mind. This holds especially true for quantitation of CrT polypeptides by Western blots, e.g. when trying to answer whether CrT's are up- or down-regulated by certain experimental interventions or under pathological conditions.

In conclusion, we still hold to the scheme that besides the high-affinity and high-efficiency plasmalemma CrT there exists an additional low affinity high Km Cr uptake mechanism in mitochondria. However, the exact biochemical nature of this mitochondrial creatine transport, still remains elusive. Finally, similar to the creatine kinase (CK) isoenzymes, which are specifically located at different cellular compartments, also the substrates of CK are compartmentalized in cytosolic and mitochondrial pools. This is in line with 14C-Cr-isotope tracer studies and a number of [31P]-NMR magnetization transfer studies, as well as with recent [1H]-NMR spectroscopy data.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Braissant O, Henry H, Loup M, Eilers B, Bachmann C: Endogenous synthesis and transport of creatine in the rat brain: An in situ hybridization study (1). Brain Res Mol Brain Res. 86: 193–201, 2001

    Article  PubMed  Google Scholar 

  2. Cecil KM, Salomons GS, Ball WS Jr, Wong B, Chuck G, Verhoeven NM, Jakobs C, DeGrauw TJ: Irreversible brain creatine deficiency with elevated serum and urine creatine: A creatine transporter defect? Ann Neurol 49: 401–404, 2001

    PubMed  Google Scholar 

  3. Salomons GS, van Dooren SJ, Verhoeven NM, Cecil KM, Ball WS, Degrauw TJ, Jakobs C: X-linked creatine-transporter gene (SLC6A8) defect: A new creatine-deficiency syndrome. Am J Hum Genet 68: 1497–500, 2001

    Article  PubMed  Google Scholar 

  4. Stöckler S, Hanefeld F, Frahm J: Creatine replacement therapy in guanidinoacetate methyltransferase deficiency, a novel inborn error of metabolism. Lancet 348: 789–790, 1996

    Article  PubMed  Google Scholar 

  5. Stöckler S, Isbrandt D, Hanefeld F, Schmidt B, von Figura K: Guanidinoacetate methyltransferase deficiency: The first inborn error of creatine metabolism in man. Am J Hum Genet 58: 914–922, 1996

    PubMed  Google Scholar 

  6. Stöckler S, Marescau B, De Deyn PP, Trijbels JM, Hanefeld F: Guanidino compounds in guanidinoacetate methyltransferase deficiency, a new inborn error of creatine synthesis. Metabolism 46: 1189–1193, 1997

    Article  PubMed  Google Scholar 

  7. Bizzi A, Bugiani M, Salomons GS, Hunneman DH, Moroni I, Estienne M, Danesi U, Jakobs C, Uziel G: X-linked creatine deficiency syndrome: A novel mutation in creatine transporter gene SLC6A8. Ann Neurol 52: 227–231, 2002

    Article  PubMed  Google Scholar 

  8. Cecil KM, DeGrauw TJ, Salomons GS, Jakobs C, Egelhoff JC, Clark JF: Magnetic resonance spectroscopy in a 9-day-old heterozygous female child with creatine transporter deficiency. J Comput Assist Tomogr 27: 44–47, 2003

    Article  PubMed  Google Scholar 

  9. Wyss M, Schulze A: Health implications of creatine: Can oral creatine supplementation protect against neurological and atherosclerotic disease? Neuroscience 112: 243–260, 2002

    Article  PubMed  Google Scholar 

  10. Item CB, S-I S, Stromberger C, Muhl A, Alessandri MG, Bianchi MC, Tosetti M, Fornai F, Cioni G: Arginine:glycine amidinotransferase deficiency: The third inborn error of creatine metabolism in humans. Am J Hum Genet 69: 1127–1133, 2001

    Article  PubMed  Google Scholar 

  11. Stöckler S, Holzbach U, Hanefeld F, Marquardt I, Helms G, Requart M, Hanicke W, Frahm J: Creatine deficiency in the brain: A new, treatable inborn error of metabolism. Pediatr Res 36: 409–413, 1994

    PubMed  Google Scholar 

  12. van der Knaap MS, Verhoeven NM, Maaswinkel-Mooij P, Pouwels PJ, Onkenhout W, Peeters EA, Stockler-Ipsiroglu S, Jakobs C: Mental retardation and behavioral problems as presenting signs of a creatine synthesis defect. Ann Neurol 47: 540–543, 2000

    Article  PubMed  Google Scholar 

  13. Wyss M, Kaddurah-Daouk R: Creatine and creatinine metabolism. Physiol Rev 80: 1107–1213, 2000

    PubMed  Google Scholar 

  14. Snow RJ, Murphy RM: Creatine and the creatine transporter: A review. Mol Cell Biochem 224: 169–181, 2001

    PubMed  Google Scholar 

  15. Wallimann T, Hemmer W: Creatine kinase in non-muscle tissues and cells. Mol Cell Biochem 133–134: 193–220, 1994

    Article  Google Scholar 

  16. Wallimann T, Wyss M, Brdiczka D, Nicolay K, Eppenberger HM: Intracellular compartmentation, structure and function of creatine kinase isoenzymes in tissues with high and fluctuating energy demands: The ‘phosphocreatine circuit’ for cellular energy homeostasis. Biochem J 281: 21–40, 1992

    PubMed  Google Scholar 

  17. Guerrero-Ontiveros ML, W T: 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, 1998

    Article  PubMed  Google Scholar 

  18. Hemmer W, Riesinger I, Wallimann T, Eppenberger HM, Quest AF: Brain-type creatine kinase in photoreceptor cell outer segments: Role of a phosphocreatine circuit in outer segment energy metabolism and phototransduction. J Cell Sci 106: 671–683, 1993

    PubMed  Google Scholar 

  19. Hemmer W, Wallimann T: Functional aspects of creatine kinase in brain. Dev Neurosci 15: 249–260, 1993

    PubMed  Google Scholar 

  20. Ishida Y, Riesinger I, Wallimann T, Paul RJ: Compartmentation of ATP synthesis and utilization in smooth muscle: Roles of aerobic glycolysis and creatine kinase. Mol Cell Biochem 133–134: 39–50, 1994

    Article  Google Scholar 

  21. Bessman SP, Carpenter CL: The creatine-creatine phosphate energy shuttle. Annu Rev Biochem 54: 831–862, 1985

    Article  PubMed  Google Scholar 

  22. Walker JB: Creatine: Biosynthesis, regulation, and function. Adv Enzymol Relat Areas Mol Biol 50: 177–242, 1979

    PubMed  Google Scholar 

  23. Walker JB, Hannan JK: Creatine biosynthesis during embryonic development. False feedback suppression of liver amidinotransferase by N-acetimidoylsarcosine and 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine). Biochemistry 15: 2519–2522, 1976

    Article  PubMed  Google Scholar 

  24. Magri E, Baldoni G, Grazi E: On the biosynthesis of creatine. Intramitochondrial localization of transamidinase from rat kidney. FEBS Lett 55: 91–93, 1975

    Article  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

  26. Fitch CD, S R, Payne WF, Dacus JM: Creatine metabolism in skeletal muscle. 3. Specificity of the creatine entry process. J Biol Chem 243: 2024–2027, 1968

    PubMed  Google Scholar 

  27. 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 

  28. Peral MJ, Garcia-Delgado M, Calonge ML, Duran JM, De La Horra MC, Wallimann T, Speer O, Ilundain A: Human, rat and chicken small intestinal Na(+)-Cl(−)-creatine transporter: Functional, molecular characterization and localization. J Physiol 545: 133–144, 2002

    Article  PubMed  Google Scholar 

  29. Walzel B, Speer O, Boehm E, Kristiansen S, Chan S, Clarke K, Magyar JP, Richter EA, Wallimann T: New creatine transporter assay and identification of distinct creatine transporter isoforms in muscle. Am J Physiol Endocrinol Metab 283: E390–E401, 2002

    PubMed  Google Scholar 

  30. Zhao CR, Shang L, Wang W, Jacobs DO: Myocellular creatine and creatine transporter serine phosphorylation after starvation. J Surg Res 105: 10–16, 2002

    Article  PubMed  Google Scholar 

  31. Wang W, Jobst MA, Bell B, Zhao CR, Shang LH, Jacobs DO: Cr supplementation decreases tyrosine phosphorylation of the CreaT in skeletal muscle during sepsis. Am J Physiol Endocrinol Metab 282: E1046–E1054, 2002

    PubMed  Google Scholar 

  32. Wang W, Shang LH, Jacobs DO: Complement regulatory protein CD59 involves c-SRC related tyrosine phosphorylation of the creatine transporter in skeletal muscle during sepsis. Surgery 132: 334–340, 2002

    Article  PubMed  Google Scholar 

  33. Walzel B, Speer O, Zanolla E, Eriksson O, Bernardi P, Wallimann T: Novel mitochondrial creatine transport activity. Implications for intracellular creatine compartments and bioenergetics. J Biol Chem 277: 37503–37511, 2002

    Article  PubMed  Google Scholar 

  34. Hebisch S, Sies H, Soboll S: Function dependent changes in the subcellular distribution of high energy phosphates in fast and slow rat skeletal muscles. Pflügers Arch 406: 20–24, 1986

    Article  Google Scholar 

  35. Soboll S, Conrad A, Eistert A, Herick K, Kramer R: Uptake of creatine phosphate into heart mitochondria: A leak in the creatine shuttle. Biochim Biophys Acta 1320: 27–33, 1997

    PubMed  Google Scholar 

  36. Hahn KA, Salomons GS, Tackels-Horne D, Wood TC, Taylor HA, Schroer RJ, Lubs HA, Jakobs C, Olson RL, Holden KR, Stevenson RE, Schwartz CE: X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28. Am J Hum Genet 70: 1349–1356, 2002

    Article  PubMed  Google Scholar 

  37. Ades LC, Gedeon AK, Wilson MJ, Latham M, Partington MW, Mulley JC, Nelson J, Lui K, Sillence DO: Barth syndrome: Clinical features and confirmation of gene localisation to distal Xq28. Am J Med Genet 45: 327–334, 1993

    Article  PubMed  Google Scholar 

  38. Bolhuis PA, Hensels GW, Hulsebos TJ, Baas F, Barth PG: Mapping of the locus for X-linked cardioskeletal myopathy with neutropenia and abnormal mitochondria (Barth syndrome) to Xq28. Am J Hum Genet 48: 481–485, 1991

    PubMed  Google Scholar 

  39. Consalez GG, Thomas NS, Stayton CL, Knight SJ, Johnson M, Hopkins LC, Harper PS, Elsas LJ, Warren ST: Assignment of Emery-Dreifuss muscular dystrophy to the distal region of Xq28: The results of a collaborative study. Am J Hum Genet 48: 468–480, 1991

    PubMed  Google Scholar 

  40. Thomas NS, Williams H, Cole G, Roberts K, Clarke A, Liechti-Gallati S, Braga S, Gerber A, Meier C, Moser H et al.: X linked neonatal centronuclear/myotubular myopathy: Evidence for linkage to Xq28 DNA marker loci. J Med Genet 27: 284–287, 1990

    PubMed  Google Scholar 

  41. Gregor P, Nash SR, Caron MG, Seldin MF, Warren ST: Assignment of the creatine transporter gene (SLC6A8) to human chromosome Xq28 telomeric to G6PD. Genomics 25: 332–333, 1995

    Article  PubMed  Google Scholar 

  42. Nash SR, Giros B, Kingsmore SF, Rochelle JM, Suter ST, Gregor P, Seldin MF, Caron MG: Cloning, pharmacological characterization, and genomic localization of the human creatine transporter. Recept Channels 2: 165–174, 1994

    PubMed  Google Scholar 

  43. Kekelidze T, Khait I, Togliatti A, Holtzman D: Brain creatine kinase and creatine transporter proteins in normal and creatine-treated rabbit pups. Dev Neurosci 22: 437–443, 2000

    Article  PubMed  Google Scholar 

  44. Tran TT, Dai W, Sarkar HK: Cyclosporin A inhibits creatine uptake by altering surface expression of the creatine transporter. J Biol Chem 275: 35708–35714, 2000

    Article  PubMed  Google Scholar 

  45. Dodd JR, Christie DL: Cysteine 144 in the third transmembrane domain of the creatine transporter is located close to a substrate-binding site. J Biol Chem 276: 46983–46988, 2001

    Article  PubMed  Google Scholar 

  46. Blakely RD, De Felice LJ, Hartzell HC: Molecular physiology of norepinephrine and serotonin transporters. J Exp Biol 196: 263–281, 1994

    PubMed  Google Scholar 

  47. Nelson N: The family of Na+/Cl− neurotransmitter transporters. J Neurochem 71: 1785–1803, 1998

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  49. Boehm E, Chan S, Monfared M, Wallimann T, Clarke K, Neubauer S: Creatine transporter activity and content in the rat heart supplemented by and depleted of creatine. Am J Physiol Endocrinol Metab 284: E399–E406, 2003

    PubMed  Google Scholar 

  50. 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 

  51. Schloss P, Mayser W, Betz H: The putative rat choline transporter CHOT1 transports creatine and is highly expressed in neural and muscle-rich tissues. Biochem Biophys Res Commun 198: 637–645, 1994

    Article  PubMed  Google Scholar 

  52. Gonzalez AM, Uhl GR: ‘Choline/orphan V8–2–1/creatine transporter’ mRNA is expressed in nervous, renal and gastrointestinal systems. Brain Res Mol Brain Res 23: 266–270, 1994

    Article  PubMed  Google Scholar 

  53. Neubauer S, Remkes H, Spindler M, Horn M, Wiesmann F, Prestle J, Walzel B, Ertl G, Hasenfuss G, Wallimann T: Downregulation of the Na(+)-creatine cotransporter in failing human myocardium and in experimental heart failure. Circulation 100: 1847–1850, 1999

    PubMed  Google Scholar 

  54. Murphy R, McConell G, Cameron-Smith D, Watt K, Ackland L, Walzel B, Wallimann T, Snow R: Creatine transporter protein content, localization, and gene expression in rat skeletal muscle. Am J Physiol Cell Physiol 280: C415–C422, 2001

    PubMed  Google Scholar 

  55. Brault JJ, Terjung RL: Creatine uptake and creatine transporter expression among rat skeletal muscle fiber types. Am J Physiol Cell Physiol 5: 5, 2003

    Google Scholar 

  56. Miller K, Sharer K, Suhan J, Koretsky AP: Expression of functional mitochondrial creatine kinase in liver of transgenic mice. Am J Physiol 272: C1193–C1202, 1997

    PubMed  Google Scholar 

  57. Queiroz MS, Shao Y, Berkich DA, Lanoue KF, Ismail-Beigi F: Thyroid hormone regulation of cardiac bioenergetics: Role of intracellular creatine. Am J Physiol Heart Circ Physiol 283: H2527–H2533, 2002

    PubMed  Google Scholar 

  58. Sora I, Richman J, Santoro G, Wei H, Wang Y, Vanderah T, Horvath R, Nguyen M, Waite S, Roeske WR et al.: The cloning and expression of a human creatine transporter. Biochem Biophys Res Commun 204: 419–427, 1994

    Article  PubMed  Google Scholar 

  59. Afolayan A, Daini OA: Isolation and properties of creatine kinase from the breast muscle of tropical fruit bat, Eidolon helvum (Kerr). Comp Biochem Physiol B 85: 463–468, 1986

    Article  PubMed  Google Scholar 

  60. Wolfel R, Halbrugge T, Graefe KH: Effects of N-ethylmaleimide on 5-hydroxytryptamine transport and sodium content in rabbit platelets. Br J Pharmacol 97: 1308–1314, 1989

    PubMed  Google Scholar 

  61. Sandoval N, Bauer D, Brenner V, Coy JF, Drescher B, Kioschis P, Korn B, Nyakatura G, Poustka A, Reichwald K, Rosenthal A, Platzer M: The genomic organization of a human creatine transporter (CRTR) gene located in Xq28, Genomics 35: 383–385, 1996

    Article  PubMed  Google Scholar 

  62. Guimbal C, Kilimann MW: A creatine transporter cDNA from Torpedo illustrates structure/function relationships in the GABA/noradrenaline transporter family. J Mol Biol 241: 317–324, 1994

    Article  PubMed  Google Scholar 

  63. Hovius R, Lambrechts H, Nicolay K, de Kruijff B: Improved methods to isolate and subfractionate rat liver mitochondria. Lipid composition of the inner and outer membrane. Biochim Biophys Acta 1021: 217–226, 1990

    PubMed  Google Scholar 

  64. Brdiczka D, Pette D, Brunner G, Miller F: Compartmental dispersion of enzymes in rat liver mitochondria. Eur J Biochem 5: 294–304, 1968

    Article  PubMed  Google Scholar 

  65. Kristiansen S, Hargreaves M, Richter EA: Exercise-induced increase in glucose transport, GLUT-4, and VAMP-2 in plasma membrane from human muscle. Am J Physiol 270: E197–E201, 1996

    PubMed  Google Scholar 

  66. Gorg A, Obermaier C, Boguth G, Harder A, Scheibe B, Wildgruber R, Weiss W: The current state of two-dimensional electrophoresis with immobilized pH gradients. Electrophoresis 21: 1037–1053, 2000

    Article  PubMed  Google Scholar 

  67. Brusca JS, Radolf JD: Isolation of integral membrane proteins by phase partitioning with Triton X-114. Meth Enzymol 228: 182–193, 1994

    PubMed  Google Scholar 

  68. Fujiki Y, Hubbard AL, Fowler S, Lazarow PB: Isolation of intracellular membranes by means of sodium carbonate treatment: Application to endoplasmic reticulum. J Cell Biol 93: 97–102, 1982

    Article  PubMed  Google Scholar 

  69. Suzuki H, Okazawa Y, Komiya T, Saeki K, Mekada E, Kitada S, Ito A, Mihara K: Characterization of rat TOM40, a central component of the preprotein translocase of the mitochondrial outer membrane. J Biol Chem 275: 37930–37936, 2000

    Article  PubMed  Google Scholar 

  70. Neukomm L: Identification of antigens recognized by anti-creatine transporter antibodies in rat liver mitochondria. Zürich: Swiss Federal Technical Highschool, ETH, 2002

    Google Scholar 

  71. Maas E, Bisswanger H: Localization of the alpha-oxoacid dehydrogenase multienzyme complexes within the mitochondrion. FEBS Lett 277: 189–190, 1990

    Article  PubMed  Google Scholar 

  72. Tarnopolsky P: Walzel, Schlattner, Wallimann creatine transporter and mitochondrial creatine kinase protein content in myopathies: Significant reduction of creatine transporters in myopathies. Muscle Nerve 24: 682–688, 2001

    Article  PubMed  Google Scholar 

  73. Murphy R, Tunstall R, Mehan K, Cameron-Smith D, McKenna MJ, Spriet LMH, Snow R: Human skeletal muscle creatine transporter mRNA and protein expression in males and females. Mol Cell Biochem 244: 151–157, 2003

    Article  PubMed  Google Scholar 

  74. Dodd JR, Zheng T, Christie DL: Creatine accumulation and exchange by HEK293 cells stably expressing high levels of a creatine transporter. Biochim Biophys Acta 1472: 128–136, 1999

    PubMed  Google Scholar 

  75. Bassendine MF, Jones DE, Yeaman SJ: Biochemistry and autoimmune response to the 2-oxoacid dehydrogenase complexes in primary biliary cirrhosis. Semin Liver Dis 17: 49–60., 1997

    PubMed  Google Scholar 

  76. Nishio A, Coppel R, Ishibashi H, Gershwin ME: The pyruvate dehydrogenase complex as a target autoantigen in primary biliary cirrhosis. Baillieres Best Pract Res Clin Gastroenterol 14: 535–547, 2000

    Article  PubMed  Google Scholar 

  77. Mackay IR, Whittingham S, Fida S, Myers M, Ikuno N, Gershwin ME, Rowley MJ: The peculiar autoimmunity of primary biliary cirrhosis. Immunol Rev 174: 226–237, 2000

    Article  PubMed  Google Scholar 

  78. Tanaka A, Nalbandian G, Leung PS, Benson GD, Munoz S, Findor JA, Branch AD, Coppel RL, Ansari AA, Gershwin ME: Mucosal immunity and primary biliary cirrhosis: Presence of antimitochondrial antibodies in urine. Hepatology 32: 910–915, 2000

    Article  PubMed  Google Scholar 

  79. Reynoso-Paz S, Leung PS, Van De Water J, Tanaka A, Munoz S, Bass N, Lindor K, Donald PJ, Coppel RL, Ansari AA, Gershwin ME: Evidence for a locally driven mucosal response and the presence of mitochondrial antigens in saliva in primary biliary cirrhosis. Hepatology 31: 24–29, 2000

    Article  PubMed  Google Scholar 

  80. Yeaman SJ, Kirby JA, Jones DE: Autoreactive responses to pyruvate dehydrogenase complex in the pathogenesis of primary biliary cirrhosis. Immunol Rev 174: 238–249, 2000

    Article  PubMed  Google Scholar 

  81. Saltarelli MD, Bauman AL, Moore KR, Bradley CC, Blakely RD: Expression of the rat brain creatine transporter in situ and in transfected HeLa cells. Dev Neurosci 18: 524–534, 1996

    PubMed  Google Scholar 

  82. 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 

  83. Dai W, Vinnakota S, Qian X, Kunze DL, Sarkar HK: Molecular characterization of the human CRT-1 creatine transporter expressed in Xenopus oocytes. Arch Biochem Biophys 361: 75–84, 1999

    Article  PubMed  Google Scholar 

  84. Hochachka PW, Mossey MK: Does muscle creatine phosphokinase have access to the total pool of phosphocreatine plus creatine? Am J Physiol 274: R868–R872, 1998

    PubMed  Google Scholar 

  85. Joubert F, Gillet B, Mazet JL, Mateo P, Beloeil J, Hoerter JA: Evidence for myocardial ATP compartmentation from NMR inversion transfer analysis of creatine kinase fluxes. Biophys J 79: 1–13, 2000

    PubMed  Google Scholar 

  86. Kreis R, Jung B, Slotboom J, Felblinger J, Boesch C: Effect of exercise on the creatine resonances in 1H MR spectra of human skeletal muscle. J Magn Reson 137: 350–357, 1999

    Article  PubMed  Google Scholar 

  87. Zorzano A, Fandos C, Palacin M: Role of plasma membrane transporters in muscle metabolism. Biochem J 349: 667–688, 2000

    PubMed  Google Scholar 

  88. Powers-Lee SG, Mastico RA, Bendayan M: The interaction of rat liver carbamoyl phosphate synthetase and ornithine transcarbamoylase with inner mitochondrial membranes. J Biol Chem 262: 15683–15688, 1987

    PubMed  Google Scholar 

  89. Bollard ME, Murray AJ, Clarke K, Nicholson JK, Griffin JL: A study of metabolic compartmentation in the rat heart and cardiac mitochondria using high-resolution magic angle spinning H-NMR spectroscopy. FEBS Lett 553: 73–78

  90. Menin L, Panchichkina M, Keriel C, Olivares J, Braun U, Seppet EK, Saks VA: Macrocompartmentation of total creatine in cardiomyocytes revisted. Mol Cell Biochem 220: 149–159, 2001

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. ETH-Zürich, Institute of Cell Biology, ETH-Hönggerberg, CH-8093, Zurich, Switzerland

    Oliver Speer, Lukas J. Neukomm, Elsa Zanolla, Uwe Schlattner & Theo Wallimann

  2. School of Health Sciences, Deakin University, 221 Burwood Highway, urwood, 3125, Australia

    Robyn M. Murphy & Rodney J. Snow

  3. University Hospital, Clinical Chemistry Laboratories, Lausanne, Switzerland

    Hugues Henry

Authors
  1. Oliver Speer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lukas J. Neukomm
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robyn M. Murphy
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Elsa Zanolla
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Uwe Schlattner
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Hugues Henry
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rodney J. Snow
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Theo Wallimann
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Speer, O., Neukomm, L.J., Murphy, R.M. et al. Creatine transporters: A reappraisal. Mol Cell Biochem 256, 407–424 (2004). https://doi.org/10.1023/B:MCBI.0000009886.98508.e7

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MCBI.0000009886.98508.e7

Search

Navigation