Ebook: Technological and Medical Implications of Metabolic Control Analysis

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.

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The study of multienzyme systems has advanced considerably during the least decade. The cell is more complicated than classical biochemistry presents it, it contains more structure, and the behaviour of any system of enzymes is more elaborate than can be explained in simple terms. Nevertheless, classical enzymology and metabolism remain central to any modification of the metabolic behaviour of organisms, as attempted by modern biotechnology and drug development techniques.
In this cool, objective look at the current state of the art, internationally respected authors draw attention to the drawbacks, problems, and opportunities associated with this exciting field. The areas covered include problems with current practice, the imposition of human objectives on organisms, understanding health and disease, computer modelling, the increasingly complex picture of cell structure, control and regulation of metabolism, and the general contribution metabolic control is making to biochemistry on a broader canvas.

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The study of multienzyme systems has advanced considerably during the least decade. The cell is more complicated than classical biochemistry presents it, it contains more structure, and the behaviour of any system of enzymes is more elaborate than can be explained in simple terms. Nevertheless, classical enzymology and metabolism remain central to any modification of the metabolic behaviour of organisms, as attempted by modern biotechnology and drug development techniques.
In this cool, objective look at the current state of the art, internationally respected authors draw attention to the drawbacks, problems, and opportunities associated with this exciting field. The areas covered include problems with current practice, the imposition of human objectives on organisms, understanding health and disease, computer modelling, the increasingly complex picture of cell structure, control and regulation of metabolism, and the general contribution metabolic control is making to biochemistry on a broader canvas.
Content:
Front Matter....Pages i-xiv
Front Matter....Pages 1-1
Snapshots of Systems....Pages 3-25
Moiety Conservation and Flux Enhancement....Pages 27-32
On the Universality of The Universal Method....Pages 33-37
Front Matter....Pages 39-39
Life is Complicated....Pages 41-47
Recent Developments in Metabolic Pathway Analysis and Their Potential Implications for Biotechnology and Medicine....Pages 49-56
Quantifying the Importance of Regulatory Loops in homeostatic Control Mechanisms: Hierarchical Control of DNA Supercoiling....Pages 57-66
An Integrated Approach to the Analysis of the Control and Regulation of Cellular Systems....Pages 67-72
Front Matter....Pages 73-79
Metabolic Control Analysis Shows How Aneuploidy Causes Cancer....Pages 81-81
Regulation of Energy Metabolism in Hepatocytes....Pages 83-98
Combined NMR Experimental and Computer-Simulation Study of 2,3-Bisphosphoglycerate Metabolism in Human Erythrocytes....Pages 99-107
Front Matter....Pages 109-115
Computational Approaches to the Study of Biochemical Pathways and Metabolic Control....Pages 117-123
Using Metabolic Control Analysis To Improve The Selectivity and Effectiveness of Drugs Against Parasitic Diseases....Pages 125-130
Computer Simulation as A Tool for Studying Metabolism and Drug Design....Pages 131-138
Use of Metabolic Control Analysis to Design a New Strategy for Cancer Therapy....Pages 139-145
Front Matter....Pages 147-147
Implications of Cytoarchitectural Analysis....Pages 149-155
Front Matter....Pages 157-164
Probing The Cell Interior With NMR Spectroscopy....Pages 165-172
Metabolite Channelling and Protein—Protein Interactions in the Urea Synthesis Pathway....Pages 173-180
Supramolecular Organization and Substrate Channelling in the Mammalian Translation System....Pages 181-181
Front Matter....Pages 183-190
Time-Dependent or Steady-State Control of Metabolic Systems?....Pages 181-181
Multisite Modulation in the Control of Glycolysis....Pages 191-198
Exercising Control When Control is Distributed....Pages 199-206
Glycogen Structure: an Evolutionary View....Pages 207-214
Front Matter....Pages 215-221
Metabolic Control and Metabolons in the Millennium....Pages 223-231
Back Matter....Pages 233-233
....Pages 235-242