Technological and Medical Implications of Metabolic Control Analysis

1. Provoking an Argument: Problems with Current Approaches to the Analysis of Biochemical Systems.- 1. Snapshots of systems: metabolic control analysis and biotechnology in the post-genomic era.- 2. Moiety conservation and flux enhancement.- 3. On the universality of the universal method.- 2. Imposing Discipline: Manipulation of Organisms for Technological Ends.- 4. Life is complicated.- 5. Regulation and redirection of metabolism: incorporating regulatory information influx calculation.- 6. Recent developments in metabolic pathway analysis and their potential implications for biotechnology and medicine.- 7. Quantifying the importance of regulatory loops in homeostatic control mechanisms: hierarchical control of DNA supercoiling.- 8. An integrated approach to theanalysis of the control andregulation of cellular systems.- 3. Understanding Health and Disease: Why Organisms Behave as They Do.- 9. Mechanism of carcinogenesis by polycyclic aromatic hydrocarbons: aneuploidy precedes malignant transformation and occurs in all cancers.- 10. Metabolic control analysis shows how aneuploidy causes cancer.- 11. The control strength of glucokinase in hepatocytes: a predictor of metabolic defects in maturity onset diabetes of the young, type 2.- 12. Metabolic distress associated with impaired control by alternative substrates: two examples taken from purine metabolism.- 13. Regulation of ATP supply in muscle: implications for importance of flux control coefficients and for the genesis of mitochondrial myopathies.- 14. Regulation of energy metabolism in hepatocytes.- 15. Combined NMR experimental and computer-simulation study of 2,3-bisphosphoglycerate metabolism in human erythrocytes.- 4. Taking Aim: Use of Metabolic Models to Identify Drug Targets.- 16. Computational approaches to the study of biochemical pathways and metabolic control.- 17. Using metabolic control analysis to improve the selectivity and effectiveness of drugs against parasitic diseases.- 18. Computer simulation as a tool for studying metabolism and drug design.- 19. Use of metabolic control analysis to design a new strategy for cancer therapy.- 5. Facing Reality: Not Just a Bag of Enzymes.- 20. Implications of cytoarchitectural analysis.- 21. Probing the cell interior with NMR spectroscopy.- 22. Metabolite channelling and protein-protein interactions in the urea synthesis pathway.- 23. Intracellular distribution of glycogen synthase: Another regulatory mechanism of glycogen metabolism?.- 24. Supramolecular organization and substrate channelling in the mammalian translation system.- 25. Analysis of co-localization of glycolytic enzymes in flight muscle and its relation to muscle function in Drosophila.- 6. Thinking About Metabolism: The Relationship Between Control and Regulation.- 26. Metabolic control from the back benches: biochemistry towards biocomplexity.- 27. Physiological consequences of a non-regulated mutant phosphofructokinase in Escherichia coli.- 28. Time-dependent or steady-state control of metabolic systems?.- 29. Multisite modulation in the control of glycolysis: balance of supply and demand?.- 30. Exercising control when control is distributed.- 31. Metabolic control design: implications and applications.- 32. Determining elasticities in situ.- 33. Coordination and homeostasis in the response to multiple signals: role of metabolic cascades.- 34. Putting the cart before the horse: designing a metabolic system in order to understand it.- 35. Predicting the structural design of metabolic pathways: an evolutionary approach.- 36. Glycogen structure: an evolutionary view.- 7. Taking Stock: Control Analysis in the Context of Metabolic Regulation.- 37. From control to regulation: a new prospect for metabolic control analysis.- 38. Metabolic control and metabolons in the millennium.- In memoriam: Paul Srere, 1925-1999.- A. Cornish-Bowden.- Contributors.