Regulation of HMG-CoA Reductase

Regulation of HMG-CoA Reductase is a nine-chapter text that focuses on the research developments in the regulation of HMG-CoA reductase enzyme and cholesterol biosynthesis.
This book deals first with the role of cholesterol in the regulation of its own biosynthesis and the work involving compactin and related competitive inhibitors of HMG-CoA reductase. The subsequent chapters examine the reversible phosphorylation of HMG-CoA reductase in hormonal and other short-term physiological changes and the structure and properties of the enzyme, including evidence for modulation of enzyme activity and structure unrelated to phosphorylation. These topics are followed by discussions on the regulation of reductase in the biosynthesis of ubiquinone, dolichols, and isopentenyl-tRNA and the regulation of reductase activity in extrahepatic tissues. This text further explores the contributions made through the use of cultured cells and their genetic manipulation, with emphasis on the great potential of this approach. The concluding chapters address the status of the low-density lipoprotein pathway and related mechanisms. These chapters also consider the regulation of human hepatic HMG-CoA reductase and the special problems inherent in work with human tissues.
Enzyme scientists and researchers and graduate students will find this book invaluable.

Contenu

Contributors
Preface
1 Membrane-Mediated Control of Reductase Activity
I. Introduction
II. Regulation of HMG-CoA Reductase Activity
III. The Concept of Feedback Inhibition in Cholesterogenesis
IV. Relationship between Cellular Cholesterol Concentration and HMG-CoA Reductase Activity
V. Architectural Organization of Biological Membranes
VI. Modulation of HMG-CoA Reductase by Nonesterified Cholesterol
VII. Conclusions and Prospectives
References
2 Specific Nonsterol Inhibitors of HMG-CoA Reductase
I. Introduction
II. Isolation and Chemistry of Compactin (ML-236B)-Related Compounds
III. Inhibition of HMG-CoA Reductase
IV. Inhibition of Sterol and Other Isoprenoid Syntheses
V. Induction of HMG-CoA Reductase
VI. Growth Inhibition
VII. Compactin-Resistant Cells
VIII. Relationship between the Effects of Compactin and Oxygenated Sterols on HMG-CoA Reductase
IX. Hypocholesterolemic Activity
X. Summary and Conclusion
References
3 Reversible Phosphorylation of Hepatic HMG-CoA Reductase in Endocrine and Feedback Control of Cholesterol Biosynthesis
I. Introduction
II. Short-Term Control of HMG-CoA Reductase
III. Biological Significance of Reversible Phosphorylation of HMG-CoA Reductase
References
4 Studies on Purified Mammalian HMG-CoA Reductase and Regulation of Enzyme Activity
I. Introduction
II. Purification of HMG-CoA Reductase
III. Different Forms of HMG-CoA Reductase
IV. Structure of the Microsomal-Bound Enzyme
V. Enzyme Regulation
References
5 Regulation of HMG-CoA Reductase and the Biosynthesis of Nonsteroid Prenyl Derivatives
I. Introduction
II. Biosynthesis of Ubiquinone
III. Biosynthesis of Dolichols
IV. Isopentenyl Transfer RNA and Its Metabolites
V. Other Isoprenoid Derivatives of Mevalonate
VI. Overview of the Regulation of Isoprenoid Biosynthesis
References
6 Regulation of HMG-CoA Reductase in Extrahepatic Tissues
I. Introduction
II. Intestinal HMG-CoA Reductase
III. HMG-CoA Reductase in Steroid-Hormone-Producing Tissues
IV. Conclusions
References
7 Somatic Cell Genetic Analysis of Cholesterol Biosynthesis
I. Introduction
II. Cholesterol Auxotrophs
III. 25-Hydroxycholesterol-Resistant Mutants
IV. Compactin-Resistant Variants
V. Somatic Cell Mutants Defective in Internalization of Low Density Lipoprotein
VI. Analysis of the Effect of Membrane Cholesterol Levels on Membrane Structure and Function
References
8 Plasma Lipoproteins and 3-Hydroxy-3-methylglutaryl-coenzyme A Reductase: A Status Report
I. Introduction
II. Plasma Lipoproteins
III. Lipoprotein Synthesis and Secretion
IV. Lipoprotein Dynamics
V. Intravascular Lipoprotein Metabolism
VI. Receptor-Mediated Uptake of Plasma Lipoproteins
VII. Nonreceptor-Mediated Cellular Uptake of Cholesterol and Lipoproteins
VIII. Regulation of Gene Expression
IX. Summary and Future Directions
References
9 Regulation of HMG-CoA Reductase in Human Liver
I. Introduction
II. Overall Aspects of Cholesterol Metabolism in Humans
III. Assay and Properties of Hepatic Microsomal HMG-CoA Reductase in Humans
IV. Studies on Clinical Conditions
V. Studies Using Experimental Perturbations
VI. Conclusions and Implications for Future Work
References
Reductase: Future Directions
Index