Creatine and Creatine Phosphate (eBook)

Front Cover 1
Creatine and Creatine Phosphate: Scientific and Clinical Perspectives 2
Copyright Page 5
Contents 6
List of Contributors 10
A Brief Review of the Sections 12
Preface 14
Acknowledgements 15
Section I: Basic Biochemistry of Creatine and Creatine Phosphate 16
Chapter 1. Old and New Ideas on the Roles of Phosphagens and their Kinases 18
1. Historical introduction to phosphagen kinases 18
2. Physiological functions of phosphagen kinases 20
3. Use of creatine kinase by the biochemist and physiologist 23
4. The phosphoglycerate kinase-glyceraldehyde 3-phosphate dehydrogenase (GAPDH) method 24
5. Comparison of the free ADP concentration estimated by different methods 25
6. Determination of the amount of ADP irreversibly bound to structural protein in the domestic fowl pectoral muscle 26
References 28
Chapter 2. Creatine Phosphate Shuttle Pathway in Tissues with Dynamic Energy Demand 32
1. Creatine phosphate shuttle hypothesis: cytosolic and mitochondrial CK serve as components of the shuttle 32
2. CK in specialized cells: biochemical, physiological and immunological characterization 34
3. Subcellular localization of CK 37
4. Structure-function analysis of CK 38
5. Targeted modification of CK 40
6. Future applications 41
7. Summary 42
Acknowledgements 43
References 43
Chapter 3. Experimental Observations of Creatine and Creatine Phosphate Metabolism 48
1. Introduction 48
2. NMR studies of ATP and creatine phosphate in the heart 49
3. Creatine phosphate metabolism investigated with ß-guanidinopropionic acid 51
4. Creatine phosphate in skeletal muscle 54
5. Creatine transport 56
6. Summary 61
References 61
Chapter 4. An Introduction to the Cellular Creatine Kinase System in Contractile Tissue 66
1. Introduction 66
2. The creatine kinase system in different muscle types 67
3. Skeletal muscle 68
4. Cardiac muscle 69
5. Smooth muscle 74
6. Summary 76
References 77
Chapter 5. Cardiac Energetics: Compartmentation of Creatine Kinase and Regulation of Oxidative Phosphorylation 80
1. Introduction 80
2. The role of the outer mitochondrial membrane in restricting ADP diffusion and controlling respiration 81
3. Metabolic oscillations in cytoplasm as a feedback signal 87
References 91
Chapter 6. The Role of the Creatine Kinase/Creatine Phosphate System Studied by Molecular Biology 94
1. Introduction 94
2. Transgenic knock-out 95
3. Muscle performance 95
4. Graded CK knock-out 97
5. Transgenic overexpression 101
6. Summary 101
Acknowledgements 101
References 102
Section II: Biochemical Basis for a Therapeutic Role of Creatine and Creatine Phosphate 104
Chapter 7. Molecular and Cellular Mechanisms of Action for the Cardioprotective and Therapeutic Role of Creatine Phosphate 106
1. Introduction 106
2. Pharmacological effects of exogenous PCr 107
3. Calcium dependence of the anti-ischaemic effect of PCr 109
4. Protection of the heart from oxidative damage 111
5. Effects of PCr on phospholipid metabolism 112
6. Other biochemical effects related to the uptake of PCr 114
7. Pharmacokinetics of PCr uptake by different tissues 115
8. Direct effect of PCr on the cell membrane 115
9. The zwitterionic mechanism of action of PCr 117
10. Attenuation of Adriamycin cardiotoxicity by exogenous PCr 118
11. Extracellular effects of PCr 123
12. Summary 123
References 125
Chapter 8. Effects of Creatine Phosphate on Cultured Cardiac Cells 130
1. Introduction 130
2. Protection by creatine phosphate against Adriamycin 132
3. Summary 134
References 138
Section III: Magnetic Resonance Spectroscopy of Creatine Phosphate in the Cardiovascular System 140
Chapter 9. Creatine Phosphate:in vivo Human Cardiac Metabolism Studied by Magnetic Resonance Spectroscopy 142
1. Introduction 142
2. The normal heart: resting metabolism 143
3. The normal heart: isotonic and isometric exercise 146
4. Left ventricular hypertrophy 152
5. Ischaemic heart disease 158
6. Myocarditis and dilated cardiomyopathy 163
7. Cardiac transplantation 164
8. Creatine phosphate changes in tachycardia and rhythm disorders 165
9. Hypoxaemic congenital heart disease 166
10. Infiltrative conditions: amyloidosis and granulomatous cardiomyopathy 166
11. Changes in creatine phosphate: the effects of drug therapy and diagnostic potential 167
12. Summary 168
Acknowledgements 168
References 168
Chapter 10. Skeletal Muscle Metabolism in Heart Failure 176
1. Background haemodynamic and oxygen consumption studies 176
2. Abnormalities in muscle metabolism 177
3. Peripheral blood flow during exercise: relationship to metabolic changes 182
4. Skeletal muscle metabolism and blood flow in the calf muscle in controls and patients with heart failure at rest and during exercise 186
5. Skeletal muscle metabolism during recovery from exercise 188
6. Mechanisms of metabolic abnormalities in skeletal muscle in heart failure 189
7. Reversing the changes in skeletal muscle metabolism in heart failure 191
8. Summary 193
Acknowledgements 193
References 193
Section IV: Therapeutic Aspects of Creatine and Creatine Phosphate Metabolism 198
Chapter 11. Clinical Experience with Creatine Phosphate Therapy 200
I. Introduction 200
2. Heart surgery 201
3. Myocardial infarction 204
4. Heart failure 207
5. Summary 210
References 211
Chapter 12. Creatine Phosphate Added to St Thomas' Cardioplegia 214
1. Introduction 214
2. Experimental studies 215
3. Results 216
4. Clinical studies 219
5. Results 221
6. Discussion 224
7. Summary 228
References 228
Chapter 13. Uses of Creatine Phosphate and Creatine Supplementation for the Athlete 232
1. Introduction 232
2. Experimental creatine supplementation 233
3. Oral creatine supplementation 234
4. Control of nucleotide loss 236
5. Creatine phosphate 236
6. Summary 238
Acknowledgements 239
References 239
Chapter 14. Creatine and Creatine Phosphate: Future Perspectives 242
1. Future perspectives 242
References 244
Appendix 246
Assay for Creatine and Creatine Phosphate 248
Glossary 252
Index 254