Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Science 30 January 1981:
Vol. 211. no. 4481, pp. 448 - 452
DOI: 10.1126/science.6450446
Prev | Table of Contents | Next

Articles

Science, Vol 211, Issue 4481, 448-452
Copyright © 1981 by American Association for the Advancement of Science

articles

Transport of energy in muscle: the phosphorylcreatine shuttle

SP Bessman and PJ Geiger

In order to explain the insulin-like effect of exercise, it was proposed in 1951 that contracting muscle fibers liberate creatine, which acts to produce an acceptor effect--later called respiratory control--on the muscle mitochondria. The development of this notion paralleled the controversy between biochemists and physiologists over the delivery of energy for muscle contraction. With the demonstration of functional compartmentation of creatine kinase on the mitochondrion, it became clear that the actual form of energy transport in the muscle fiber is phosphorylcreatine. The finding of an isoenzyme of creatine phosphokinase attached to the M-line region of the myofibril revealed the peripheral receptor for the mitochondrially generated phosphorylcreatine. This established a molecular basis for a phosphorylcreatine-creatine shuttle for energy transport in heart and skeletal muscle and provided an explanation for the inability to demonstrate experimentally a direct relation between muscle activity and the concentrations of adenosine triphosphate and adenosine diphosphate.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The control systems structures of energy metabolism.
M. Cloutier and P. Wellstead (2009)
J R Soc Interface
   Abstract »    Full Text »    PDF »
Robust modelling, measurement and analysis of human and animal metabolic systems.
J. H.G.M. van Beek, A.-C. Hauschild, H. Hettling, and T. W. Binsl (2009)
Phil Trans R Soc A 367, 1971-1992
   Abstract »    Full Text »    PDF »
Magnetic resonance spectroscopy in myocardial disease..
L. E. Hudsmith and S. Neubauer (2009)
J. Am. Coll. Cardiol. Img. 2, 87-96
   Abstract »    Full Text »    PDF »
Muscle phosphocreatine kinetics in children and adults at the onset and offset of moderate-intensity exercise.
A. R. Barker, J. R. Welsman, J. Fulford, D. Welford, and N. Armstrong (2008)
J Appl Physiol 105, 446-456
   Abstract »    Full Text »    PDF »
Supra- and sub-baseline phosphocreatine recovery in developing brain after transient hypoxia-ischaemia: relation to baseline energetics, insult severity and outcome.
O. Iwata, S. Iwata, A. Bainbridge, E. De Vita, T. Matsuishi, E. B. Cady, and N. J. Robertson (2008)
Brain 131, 2220-2226
   Abstract »    Full Text »    PDF »
Effects of metabolic inhibition on conduction, Ca transients, and arrhythmia vulnerability in embryonic mouse hearts.
F. Chen, C. De Diego, L.-H. Xie, J.-H. Yang, T. S Klitzner, and J. N Weiss (2007)
Am J Physiol Heart Circ Physiol 293, H2472-H2478
   Abstract »    Full Text »    PDF »
Adenine nucleotide-creatine-phosphate module in myocardial metabolic system explains fast phase of dynamic regulation of oxidative phosphorylation.
J. H. G. M. van Beek (2007)
Am J Physiol Cell Physiol 293, C815-C829
   Abstract »    Full Text »    PDF »
Influence of endurance training on muscle [PCr] kinetics during high-intensity exercise.
A. M. Jones, D. P. Wilkerson, N. J. Berger, and J. Fulford (2007)
Am J Physiol Regulatory Integrative Comp Physiol 293, R392-R401
   Abstract »    Full Text »    PDF »
Cerebral energetic effects of creatine supplementation in humans.
J. W. Pan and K. Takahashi (2007)
Am J Physiol Regulatory Integrative Comp Physiol 292, R1745-R1750
   Abstract »    Full Text »    PDF »
The Failing Heart -- An Engine Out of Fuel.
S. Neubauer (2007)
N. Engl. J. Med. 356, 1140-1151
   Full Text »    PDF »
Mitochondrial Creatine Kinase Activity Prevents Reactive Oxygen Species Generation: ANTIOXIDANT ROLE OF MITOCHONDRIAL KINASE-DEPENDENT ADP RE-CYCLING ACTIVITY.
L. E. Meyer, L. B. Machado, A. P. S. A. Santiago, W. S. da-Silva, F. G. De Felice, O. Holub, M. F. Oliveira, and A. Galina (2006)
J. Biol. Chem. 281, 37361-37371
   Abstract »    Full Text »    PDF »
Thematic review series: Systems Biology Approaches to Metabolic and Cardiovascular Disorders. Network perspectives of cardiovascular metabolism.
J. N. Weiss, L. Yang, and Z. Qu (2006)
J. Lipid Res. 47, 2355-2366
   Abstract »    Full Text »    PDF »
Delayed Calf Muscle Phosphocreatine Recovery After Exercise Identifies Peripheral Arterial Disease.
D. C. Isbell, S. S. Berr, A. Y. Toledano, F. H. Epstein, C. H. Meyer, W. J. Rogers, N. L. Harthun, K. D. Hagspiel, A. Weltman, and C. M. Kramer (2006)
J. Am. Coll. Cardiol. 47, 2289-2295
   Abstract »    Full Text »    PDF »
Expression and Carbonylation of Creatine Kinase in the Quadriceps Femoris Muscles of Patients with Chronic Obstructive Pulmonary Disease.
E. Barreiro, J. Gea, G. Matar, and S. N.A. Hussain (2005)
Am. J. Respir. Cell Mol. Biol. 33, 636-642
   Abstract »    Full Text »    PDF »
Lower force and impaired performance during high-intensity electrical stimulation in skeletal muscle of GAMT-deficient knockout mice.
H. E. Kan, T. E. Buse-Pot, R. Peco, D. Isbrandt, A. Heerschap, and A. de Haan (2005)
Am J Physiol Cell Physiol 289, C113-C119
   Abstract »    Full Text »    PDF »
Phosphorylated guanidinoacetate partly compensates for the lack of phosphocreatine in skeletal muscle of mice lacking guanidinoacetate methyltransferase.
H. E Kan, W. K. J. Renema, D. Isbrandt, and A. Heerschap (2004)
J. Physiol. 560, 219-229
   Abstract »    Full Text »    PDF »
Energy metabolism in heart failure.
R. Ventura-Clapier, A. Garnier, and V. Veksler (2004)
J. Physiol. 555, 1-13
   Abstract »    Full Text »    PDF »
Creatine Protects the Immature Brain From Hypoxic-Ischemic Injury.
R. Berger, J. Middelanis, H.-M. Vaihinger, G. Mies, B. Wilken, and A. Jensen (2004)
Reproductive Sciences 11, 9-15
   Abstract »    PDF »
From the atomic nucleus to man: Nuclear magnetic resonance spectroscopy, the next horizon in diagnostic cardiology.
G. M. Pohost and J. R. Forder (2003)
J. Am. Coll. Cardiol. 42, 1594-1595
   Full Text »    PDF »
VO2 max is unaffected by altering the temporal pattern of stimulation frequency in rat hindlimb in situ.
R. T. Hepple, D. J. Krause, J. L. Hagen, and C. C. Jackson (2003)
J Appl Physiol 95, 705-711
   Abstract »    Full Text »    PDF »
Impaired oxidative phosphorylation in skeletal muscle of intrauterine growth-retarded rats.
M. A. Selak, B. T. Storey, I. Peterside, and R. A. Simmons (2003)
Am J Physiol Endocrinol Metab 285, E130-E137
   Abstract »    Full Text »    PDF »
Inhibition of the Mitochondrial Permeability Transition by Creatine Kinase Substrates. REQUIREMENT FOR MICROCOMPARTMENTATION.
M. Dolder, B. Walzel, O. Speer, U. Schlattner, and T. Wallimann (2003)
J. Biol. Chem. 278, 17760-17766
   Abstract »    Full Text »    PDF »
Phosphocreatine kinetics at the onset of contractions in skeletal muscle of MM creatine kinase knockout mice.
B. B. Roman, R. A. Meyer, and R. W. Wiseman (2002)
Am J Physiol Cell Physiol 283, C1776-C1783
   Abstract »    Full Text »    PDF »
Mitochondrial creatine kinase is critically necessary for normal myocardial high-energy phosphate metabolism.
M. Spindler, R. Niebler, H. Remkes, M. Horn, T. Lanz, and S. Neubauer (2002)
Am J Physiol Heart Circ Physiol 283, H680-H687
   Abstract »    Full Text »    PDF »
Effect of creatine supplementation on oxygen uptake kinetics during submaximal cycle exercise.
A. M. Jones, H. Carter, J. S. M. Pringle, and I. T. Campbell (2002)
J Appl Physiol 92, 2571-2577
   Abstract »    Full Text »    PDF »
Activation time of myocardial oxidative phosphorylation in creatine kinase and adenylate kinase knockout mice.
L. A. Gustafson and J. H. G. M. Van Beek (2002)
Am J Physiol Heart Circ Physiol 282, H2259-H2264
   Abstract »    Full Text »    PDF »
31P NMR Detection of Subcellular Creatine Kinase Fluxes in the Perfused Rat Heart. CONTRACTILITY MODIFIES ENERGY TRANSFER PATHWAYS.
F. Joubert, J.-L. Mazet, P. Mateo, and J. A. Hoerter (2002)
J. Biol. Chem. 277, 18469-18476
   Abstract »    Full Text »    PDF »
Effects of prior exercise on oxygen uptake and phosphocreatine kinetics during high-intensity knee-extension exercise in humans.
H B Rossiter, S A Ward, J M Kowalchuk, F A Howe, J R Griffiths, and B J Whipp (2001)
J. Physiol. 537, 291-303
   Abstract »    Full Text »    PDF »
Impaired muscular contractile performance and adenine nucleotide handling in creatine kinase-deficient mice.
M. Gorselink, M. R. Drost, W. A. Coumans, G. P. J. van Kranenburg, R. P. Hesselink, and G. J. van der Vusse (2001)
Am J Physiol Endocrinol Metab 281, E619-E625
   Abstract »    Full Text »    PDF »
Look Before You Leap.
P. Greenhaff, W. Willis, J. McMillen, and C. Donovan (2001)
J Appl Physiol 91, 1011-1013
   Full Text »    PDF »
The Cytoplasm: No Longer a Well-Mixed Bag.
J. N. Weiss and P. Korge (2001)
Circ. Res. 89, 108-110
   Full Text »    PDF »
Functional aspects of creatine kinase isoenzymes in endothelial cells.
U. K. M. Decking, C. Alves, T. Wallimann, M. Wyss, and J. Schrader (2001)
Am J Physiol Cell Physiol 281, C320-C328
   Abstract »    Full Text »    PDF »
ATP-regenerating system in the cilia of Paramecium caudatum.
M Noguchi, T Sawada, and T Akazawa (2001)
J. Exp. Biol. 204, 1063-1071
   Abstract »    PDF »
Does dietary creatine supplementation play a role in skeletal muscle metabolism and performance?.
A. Casey and P. L Greenhaff (2000)
Am. J. Clinical Nutrition 72, 607S-617
   Abstract »    Full Text »    PDF »
Creatine reduces human muscle PCr and pH decrements and Pi accumulation during low-intensity exercise.
J. Rico-Sanz (2000)
J Appl Physiol 88, 1181-1191
   Abstract »    Full Text »    PDF »
CK inhibition accelerates transcytosolic energy signaling during rapid workload steps in isolated rabbit hearts.
G. J. Harrison, M. H. van Wijhe, B. de Groot, F. J. Dijk, and J. H. G. M. van Beek (1999)
Am J Physiol Heart Circ Physiol 276, H134-H140
   Abstract »    Full Text »    PDF »
Phosphocreatine hydrolysis during submaximal exercise: the effect of FIO2.
L. J. Haseler, R. S. Richardson, J. S. Videen, and M. C. Hogan (1998)
J Appl Physiol 85, 1457-1463
   Abstract »    Full Text »    PDF »
Does muscle creatine phosphokinase have access to the total pool of phosphocreatine plus creatine?.
P. W. Hochachka and M. K. P. Mossey (1998)
Am J Physiol Regulatory Integrative Comp Physiol 274, R868-R872
   Abstract »    Full Text »    PDF »
Regulation of Creatine Kinase Isoenzymes in Human Placenta During Early, Mid-, and Late Gestation.
M. F. Thomure, M. J. Gast, N. Srivastava, and R. M. Payne (1996)
Reproductive Sciences 3, 322-327
   Abstract »    PDF »
Suppression of Creatine Kinase-catalyzed Phosphotransfer Results in Increased Phosphoryl Transfer by Adenylate Kinase in Intact Skeletal Muscle.
P. P. Dzeja, R. J. Zeleznikar, and N. D. Goldberg (1996)
J. Biol. Chem. 271, 12847-12851
   Abstract »    Full Text »    PDF »
Coupling Between Myosin ATPase Cycle and Creatine Kinase Cycle Facilitates Cardiac Actomyosin Sliding In Vitro : A Clue to Mechanical Dysfunction During Myocardial Ischemia.
M. Sata, S. Sugiura, H. Yamashita, S.-i. Momomura, and T. Serizawa (1996)
Circulation 93, 310-317
   Abstract »    Full Text »
Relation between work and phosphate metabolite in the in vivo paced mammalian heart.
R. Balaban, H. Kantor, L. Katz, and R. Briggs (1986)
Science 232, 1121-1123
   Abstract »    PDF »
Calcium Activation of Heart Mitochondrial Oxidative Phosphorylation. RAPID KINETICS OF mVO2, NADH, AND LIGHT SCATTERING.
P. R. Territo, S. A. French, M. C. Dunleavy, F. J. Evans, and R. S. Balaban (2001)
J. Biol. Chem. 276, 2586-2599
   Abstract »    Full Text »    PDF »
Cyclosporin A Inhibits Creatine Uptake by Altering Surface Expression of the Creatine Transporter.
T. T. Tran, W. Dai, and H. K. Sarkar (2000)
J. Biol. Chem. 275, 35708-35714
   Abstract »    Full Text »    PDF »
Compromised Energetics in the Adenylate Kinase AK1 Gene Knockout Heart under Metabolic Stress.
D. Pucar, E. Janssen, P. P. Dzeja, N. Juranic, S. Macura, B. Wieringa, and A. Terzic (2000)
J. Biol. Chem. 275, 41424-41429
   Abstract »    Full Text »    PDF »
Outer mitochondrial membrane permeability can regulate coupled respiration and cell survival.
M. G. Vander Heiden, N. S. Chandel, X. X. Li, P. T. Schumacker, M. Colombini, and C. B. Thompson (2000)
PNAS 97, 4666-4671
   Abstract »    Full Text »    PDF »
Adenylate kinase phosphotransfer communicates cellular energetic signals to ATP-sensitive potassium channels.
A. J. Carrasco, P. P. Dzeja, A. E. Alekseev, D. Pucar, L. V. Zingman, M. R. Abraham, D. Hodgson, M. Bienengraeber, M. Puceat, E. Janssen, et al. (2001)
PNAS 98, 7623-7628
   Abstract »    Full Text »    PDF »
Transgenic livers expressing mitochondrial and cytosolic CK: mitochondrial CK modulates free ADP levels.
N. Askenasy and A. P. Koretsky (2002)
Am J Physiol Cell Physiol 282, C338-C346
   Abstract »    Full Text »    PDF »
Activation time of myocardial oxidative phosphorylation in creatine kinase and adenylate kinase knockout mice.
L. A. Gustafson and J. H. G. M. Van Beek (2002)
Am J Physiol Heart Circ Physiol 282, H2259-H2264
   Abstract »    Full Text »    PDF »


To Advertise     Find Products

Science. ISSN 0036-8075 (print), 1095-9203 (online)