Technological and Medical Implications of Metabolic Control Analysis

1. Front Matter

   Pages i-xiv

   PDF

2. Provoking an Argument: Problems with Current Approaches to the Analysis of Biochemical Systems

   1. Front Matter

      Pages 1-1

      PDF

   2. Snapshots of Systems

      • Douglas B. Kell, Pedro Mendes

      Pages 3-25

   3. Moiety Conservation and Flux Enhancement

      • Johann M. Rohwer, Brett G. Olivier, Jan-Hendrik S. Hofmeyr

      Pages 27-32

   4. On the Universality of The Universal Method

      • Luis Acerenza

      Pages 33-37

3. Imposing Discipline: Manipulation of Organisms for Technological Ends

   1. Front Matter

      Pages 39-39

      PDF

   2. Life is Complicated

      • James E. Bailey

      Pages 41-47

   3. Regulation and Redirection of Metabolism: Incorporating regulatory information influx calculation

      • James C. Liao

      Pages 49-56

   4. Recent Developments in Metabolic Pathway Analysis and Their Potential Implications for Biotechnology and Medicine

      • Stefan Schuster, Thomas Dandekar, Klaus Mauch, Matthias Reuss, David Fell

      Pages 57-66

   5. Quantifying the Importance of Regulatory Loops in homeostatic Control Mechanisms: Hierarchical Control of DNA Supercoiling

      • Jacky L. Snoep, Coen C. van der Weijden, Heidi W. Andersen, Hans V. Westerhoff, Peter R. Jensen

      Pages 67-72

   6. An Integrated Approach to the Analysis of the Control and Regulation of Cellular Systems

      • Johann M. Rohwer, Jan-Hendrik S. Hofmeyr

      Pages 73-79

4. Understanding Health and Disease: Why Organisms Behave as They Do

   1. Front Matter

      Pages 81-81

      PDF

   2. Mechanism of Carcinogenesis by Polycyclic Aromatic Hydrocarbons: Aneuploidy precedes malignant transformation and occurs in all cancers

      • Peter Duesberg, Ruhong Li, Charlotte Rausch, Andreas Willer, Alwin Kraemer, George Yerganian et al.

      Pages 83-98

   3. Metabolic Control Analysis Shows How Aneuploidy Causes Cancer

      • David Rasnick, Peter H. Duesberg

      Pages 99-107

   4. The Control Strength of Glucokinase in Hepatocytes: A Predictor of Metabolic Defects in Maturity Onset Diabetes of the Young, Type 2

      • Loranne Agius, Susan Aiston, Christopher B. Newgard

      Pages 109-115

   5. Metabolic Distress Associated with Impaired Control by Alternative Substrates: Two Examples taken from Purine Metabolism

      • Costantino Salerno, Carlo Crifò

      Pages 117-123

   6. Regulation of ATP Supply in Muscle: Implications for Importance of Flux Control Coefficients and for the Genesis of Mitochondrial Myopathies

      • Bernard Korzeniewski

      Pages 125-130

   7. Regulation of Energy Metabolism in Hepatocytes

      • Martin D. Brand, Edward K. Ainscow

      Pages 131-138

   8. Combined NMR Experimental and Computer-Simulation Study of 2,3-Bisphosphoglycerate Metabolism in Human Erythrocytes

      • Philip W. Kuchel, Peter J. Mulquiney

      Pages 139-145

5. Taking Aim: Use of Metabolic Models to Identify Drug Targets

   1. Front Matter

      Pages 147-147

      PDF

Two decades have passed since the mechanisms of protein synthesis became well enough understood to permit the genetic modification oforganisms. An impressive amount of new knowledge has emerged from the new technology, but much ofthe promise of20years ago has notyet been fulfilled. In biotechnology, efforts to increase the yields of commercially valuable metabolites have been less successful than ex­ pected, and when they have succeeded it has often been as much from selective breeding as from new methods. The cell is more complicated than what is presented in the classical teaching of biochemistry, it contains more structure than was dreamed of 20 years ago, and the behaviour ofany systemofenzymes is more elaborate than can be explained in terms ofa single supposedly rate-limiting enzyme. Even if classical enzymology and meta­ bolism may have seemed rather unfashionable during the rise ofmolecular biology, they remain central to any modification ofthe metabolic behaviour oforganisms. As such modification is essential in much ofbiotechnology and drug development, bio­ technologists can only ignore these topics at their peril.

• behavior
• biochemistry
• biotechnology
• cell
• drug development
• enzymes
• metabolism

• Centre National de la Recherche Scientifique, Bioénergétique et Ingéniérie des Protéines, Marseille, France

  Athel Cornish-Bowden, María Luz Cárdenas

Policies and ethics