Chapter 7. The Phosphocreatine Circuit: Molecular and Cellular Physiology of Creatine Kinases, Sensitivity to Free Radicals, and Enhancement by Creatine Supplementation

Summary

This chapter contains sections titled:

• Abstract

• Phosphotransfer Enzymes: The Creatine Kinase System

  • Microcompartments: A Principle of Life

  • Subcellular Compartments and Microcompartments of CK

  • Tissue-specific Expression of Creatine Kinase Isoenzymes

  • Temporal and Spatial Buffering Functions of Creatine Kinases: The CK–Phosphocreatine Circuit

  • A Closer Look at CK (Micro)Compartments and High-energy Phosphate Channeling

  • Subcellular Compartmentation of CK at the Myofibrillar M-band: ATP Regeneration for Muscle Contraction

  • Subcellular Localization of CK at the Sarcoplasmic Reticulum and Plasma Membrane

  • Subcellular Compartments of CK at the Plasma Membrane and Functional Coupling with Na⁺/K⁺-ATPase

  • Structural and Functional Coupling of Cytosolic CK with ATP-sensitive K⁺ Channels and KCC2

  • CK Interaction with the Golgi GM130 Protein

  • Specific Compartments of Cytosolic CK with Insulin and Thrombin Signaling Pathways

  • Subcellular Compartments of CK with Glycolytic Enzymes and Targeting of Glycolytic Multi-enzyme Complexes

  • High-energy Phosphate Channeling by MtCK in Energy-transducing Mitochondrial Compartments

• Creatine Kinases and Cell Pathology

  • Mitochondrial MtCK, the Mitochondrial Permeability Transition Pore, and Apoptosis

  • Mitochondrial MtCK and Intramitochondrial Inclusions in Mitochondrial Myopathy

  • Overexpression of MtCK in Certain Malignancies

• Novel Membrane-related Functions of MtCK

  • Transfer of Lipids by Proteins That Bridge the Inner and Outer Mitochondrial Membrane

  • Lipid Transfer at Contact Sites

  • Cardiolipin Transfer and Apoptosis

  • Cardiolipin Domains and Mitochondrial Kinases

  • Perspectives: Relationship Between the Surface Exposure of Cardiolipin and Expression Levels of Mitochondrial Kinases

• Exquisite Sensitivity of the Creatine Kinase System to Oxidative Damage

  • Molecular Damage of Creatine Kinase by Oxidative and Nitrosative Stress

  • Molecular Basis of Creatine Kinase Damage

  • Functional Consequences of Oxidative Damage in Creatine Kinase

• Enhancement of Brain Functions and Neuroprotection by Creatine Supplementation

  • Creatine Metabolism and Brain Energetics

  • Disturbance of the CK System or Creatine Metabolism in the Brain

  • Body and Brain Creatine Metabolism

  • Effects of Creatine on Memory, Mental Performance, and Complex Tasks

  • Creatine Supplementation and Neurodegenerative Diseases

  • Creatine Supplementation and Acute Neurological Disorders

  • Inborn Errors of Metabolism

  • Psychiatric Disorders

  • Neurorestorative Strategies

  • Future Prospects of Creatine Supplementation as Adjuvant Therapeutic Strategy

  • Non-energy–related Effects of Creatine

  • Creatine as a Safe Nutritional Supplement and Functional Food

• References