Regulation of HMG-CoA Reductase

Regulation of HMG-CoA Reductase

1st Edition - January 28, 1985

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  • Editor: Benjamin Preiss
  • eBook ISBN: 9780323155144

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Description

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.

Table of Contents


  • 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




Product details

  • No. of pages: 342
  • Language: English
  • Copyright: © Academic Press 1985
  • Published: January 28, 1985
  • Imprint: Academic Press
  • eBook ISBN: 9780323155144

About the Editor

Benjamin Preiss

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