Regulation of HMG-CoA Reductase

1st Edition - January 28, 1985
Editor: Benjamin Preiss
Language: English
eBook ISBN:
9 7 8 - 0 - 3 2 3 - 1 5 5 1 4 - 4

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… Read more

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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.

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