Control of Metabolic Processes

THIS BOOK collects together papers given at a NATO Advanced Research Workshop held at Il Ciocco (Lucca), Italy, from the 9th to the 15th April, 1989. It sets out to present the current state of understanding of the principles governing the way fluxes and concentrations are maintained and controlled in metabolic systems. Although this is a topic that has held the interest of biochemists for many years, it is only quite recently that the methods of analysing the kinetics of multi-enzyme pathways developed over the past two decades have come to be widely discussed or applied experimentally. Many biochemists remain sceptical that the new methods offer a real advance (except in complexity) over the landmark discoveries of the 1950s and 1960s relating to inhibition of enzymes at branch-points by the end products of metabolic pathways, and the interpretation of allosteric effects and cooperativity. Even those who have become convinced that the classical ideas provide only the starting point for understanding metabolic control have been by no means unanimous in their assess­ ment of the direction in which one should advance. In this book we have tried to include all of the current points of view, including the view that the classical theories tell us all that we need to know. We have not seen it as our role as editors to paper over the cracks that exist and to pretend that we can speak to the world with one voice.

Table of Contents:
Prologue.- What should a Theory of Metabolic Control offer to the Experimenter?.- I. General Aspects of Control Theory.- 1. The Nature and Role of Theory in Metabolic Control.- 2. History and Original Thoughts on the Control Theoretic Approach.- 3. Control Analysis: a Theory that Works.- 4. Biochemical Systems Theory: Alternative Views of Metabolic Control.- 5. Comparison of Accuracy of Alternative Models for Biochemical Pathways.- 6. Modern Control Theories: a Consumers’ Test.- II. Mathematical Aspects of Control Analysis.- 7. The Structural Approach to Metabolic Control Analysis: I. Theoretical Aspects.- 8. The Structural Approach to Metabolic Control Analysis: II. Geometrical Aspects.- 9. Control Coefficients and the Matrix Method.- 10. Performance Indices in Metabolic Systems: A Criterion for Evaluating Effectiveness in Metabolic Regulation.- 11. Practical Determination of Control Coefficients in Metabolic Pathways.- III. Interconvertible Enzymes in Metabolic Control.- 12. Zero-Order Ultrasensitivity in Interconvertible Enzyme Systems.- 13. Metabolic Control by the Cyclic Cascade Mechanism: a Study of E. coli Glutamine Synthetase.- 14. Properties Needed for the Enzymes of an Interconvertible Cascade to Generate a Highly Sensitive Response.- 15. Regulation of Muscle Glycogenolysis.- IV. Methods of Applying Control Analysis to Real Systems.- 16. Methodology for Simulation of Metabolic Pathways and Calculation of Control Coefficients.- 17. Regulatory Responses and Control Analysis: Assessment of the Relative Importance of Internal Effectors.- 18. Determination of Control Coefficients by Shortening and Enzyme Titration of Metabolic Pathways.- 19. Control-Pattern Analysis of Metabolic Systems.- V. Channelling of Intermediates and the Time Domain.- 20. Control Analysisof Systems with Enzyme-Enzyme Interactions.- 21. Coupled Reactions and Channelling: their Role in the Control of Metabolism.- 22. Channelling and Channel Efficiency: Theory and Analytical Implications.- 23. Temporal Analysis of the Transition between Steady States.- 24. Sensing of Chemical Signals by Enzymes.- 25. Temporal Aspects of the Control of Metabolic Processes.- 26. Control of Metabolic Oscillations: Unpredictability, Critical Slowing Down, Optimal Stability and Hysteresis.- VI. Experimental Examples.- 27. A New Method for Estimating Enzyme Activity and Control Coefficients in vivo.- 28. Metabolic Control Analysis: Principles and Application to the Erythrocyte.- 29. Constraints in the Application of Control Analysis to the Study of Metabolism in Hepatocytes.- 30. Application of Metabolic Control Analysis to Photosynthesis: the Problem of Getting Data for an Impressive Algorithm.- 31. Application of Control Analysis to Photosynthetic Sucrose Synthesis.- 32. Application of Control Analysis to the Study of Amino Acid Metabolism.- 33. Flux Control Coefficients of Glycinamide Ribonucleotide Transformylase for de novo Purine Biosynthesis.- 34. Molecular Adaptation in the Lactose Operon.- 35. On the Control of Gene Expression.- 36. An Experimentalist’s View of Control Analysis.- Appendix A: Epilogue (H. KACSER).- Appendix B: Computer Programs for Modelling Metabolic Systems.- Contributors.