Principles of Metabolic Control in Mammalian Systems de Herman

Principles of Metabolic Control in Mammalian Systems

Herman

In this work we present the basic principles of metabolic control which we hope will serve as a foundation for the vast array of factual matter which the biochemist and the physician engaged in metabolic research must accumulate. Accordingly, we attempt to set forth these principles, along with sufficient explanation, so that the reader may apply them to the ever-expanding literature of biochemistry. If we are successful, this will provide a theoretical approach which can be applied to any given set of metabolic reactions. It is impossible to enumerate each and every biochemical reaction and pathway since such a work would be too unwieldy for efficient use. Rather, we hope our presentation of the principles of metabolic control will be sufficiently basic to be of lasting usefulness no matter how detailed biochemistry may become. We would like to be able to con dense biochemistry into a theoretical biology that will not only allow for the general treatment of any given reaction but will enable predic tions to be made as to the existence of necessary pathways and the con sequences of altered control. Such is not possible today, but this may be accomplished in the future. We believe it is now possible to institute the beginnings of such a theoretical biology.

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Cuprins

1 The Principles of Metabolic Control.- I. The First Fundamental Theorem of Theoretical Biology.- II. The Second Fundamental Theorem of Theoretical Biology.- >III. Other Fundamental Theorems of Theoretical Biology.- IV. Summary.- References.- 2 Nonequilibrium Thermodynamics, Noncovalent Forces, and Water.- I. Introduction.- II. Stability, Thermodynamics, and Biological Organization.- III. Noncovalent Forces.- IV. Water.- V. Conclusions and Implications.- Appendix I.- Appendix II: Glossary.- References.- 3 Enzymes and Coenzymes: A Mechanistic View.- I. Introduction.- II. Chemical Bonding.- III. Chemical Reactions.- IV. The Protein Nature of Enzymes.- V. Enzyme Mechanisms.- VI. Coenzymes.- VII. Evolution of Enzyme Function.- References.- 4 Modulation of Enzyme Activity.- I. Introduction.- II. Noncovalent Regulatory Mechanisms.- III. Covalent Regulatory Mechanisms.- IV. Enzyme Synthesis and Degradation.- V. Evaluation of the Physiologic Importance of Regulatory Mechanisms.- VI. Conclusion: An Overview of Regulation.- References.- 5 Regulation of Protein Biosynthesis.- I. Introduction.- II. The Mechanism of Protein Biosynthesis.- III. The Regulation of Protein Biosynthesis.- References.- 6 Degradation of Enzymes.- I. Introduction.- II. Kinetics of Enzyme Degradation.- III. Techniques for the Measurement of Enzyme Degradation.- IV. Variability of Enzyme Half-Lives.- V. Changes to Degradation Rate Constants.- VI. Intracellular Localization of Degradative Pathways.- VII. Initial Reactions in Enzyme Degradation.- VIII. Conclusions.- References.- 7 DNA Replication and the Cell Cycle.- I. Introduction.- II. Chromatin Structure.- III. The Cell Cycle.- IV. DNA Synthesis.- V. Mitosis.- VI. Gene Activation and Inactivation.- VII. Summary.- References.- 8 Servomechanisms and Oscillatory Phenomena.- I. Introduction.- II. Feedback and Feedforward Phenomena.- III. Oscillatory Phenomena.- IV. Proposed Physiological Significance of Oscillatory Phenomena.- References.- 9 Membrane-Bound Enzymes.- I. Introduction.- II. Membrane Composition and Structure.- III. Endoplasmic Reticulum.- IV. Golgi Apparatus.- V. Mitochondria.- VI. Plasma Membrane.- VII. Temperature Effects.- VIII. Conclusion: Effects of Lipids on Enzymatic Activity.- References.- 10 The Importance of Phospholipid—Protein Interactions for Regulation of the Activities of Membrane-Bound Enzymes.- I. Introduction.- II. Effect of Lipid Composition on the Properties of Membranes and Membrane-Bound Proteins.- III. The Effect of Proteins on the Properties of Membrane Lipids.- IV. The Effect of Phospholipids on the Activities of Soluble Enzymes and Proteins.- V. Reconstituted Systems.- VI. Alteration of the Properties of Tightly-Bound Membrane Enzymes by Perturbation of Their Membrane Lipid Environment.- VII. Model for Lipid—Protein Interactions.- VIII. Consideration of Factors Regulating the Activities of Membrane-Bound Enzymes in Vivo.- IX. Conclusions.- References.- 11 Membrane Structure and Transport Systems.- I. Introduction.- II. Contact Inhibition and Intercellular Communication.- III. Antigenic and Receptor Sites.- IV. Membrane Structure.- V. Membrane Composition.- VI. Transport Systems.- VII. Summary.- References.- 12 Cellular Mechanisms of Secretion.- I. Introduction.- II. Representative Secretory Cells.- III. Membrane Flow and Differentiation.- IV. Membrane Reutilization.- V. The Clinical Importance of Intracellular Membranes for Secretion.- VI. Microtubules.- VII. Mechanisms of Secretory Activation.- VIII. Types of Secretory Discharge.- IX. Summary.- References.- 13 Compartmentation andIts Role in Metabolic Regulation.- I. Introduction.- II. Nature of Intracellular Compartments.- III. Zymogen Activation and Compartmentation.- IV. Membrane Permeability and the Movement of Molecules in the Cell.- V. Examples of the Role of Compartmentation in the Regulation of Energy Metabolism.- VI. Conclusions.- References.- 14 The Mechanism of Action of Hormones.- I. Introduction.- II. Hormones.- 15 The Biochemical Basis of Disease.- I. Introduction.- II. The Biochemical Basis of Disease.- III. Therapeutic Approaches to Disease.- References.