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Cholesterol Metabolism, LDL, and the LDL Receptor focuses on the cholesterol biochemistry and lipoprotein metabolism. This book is organized into 10 chapters that describe the coordinated actions of three regulated processes, namely, the intracellular synthesis of cholesterol, its esterification by ACAT, and the receptor-mediated uptake of low-density lipoprotein (LDL), for optimal level of free cholesterol.
The first five chapters explore the various aspects of cholesterol biology, including discussions on the interaction of ligands with their cell-surface receptors; the role of coated pits in the endocytosis of receptor-bound ligands; and the recycling of receptors through the interior of the cell. These chapters also examine the regulation of gene expression encoding inducible proteins and the use of natural and synthetic mutations in studies of the functions of the separate domains of a multifunctional protein. A chapter describes the cloning of the apoB gene, the receptor-binding domain of apoB-100, and the unusual mode of derivation of apoB-48. Considerable chapters are devoted to LDL receptor and its pathway. The concluding chapter deals with the clinical consequences of genetic dysfunction of the LDL receptor, with particular emphasis on the diagnostic and treatment approaches of familial hypercholesterolemia that are based wholly or in part on knowledge of the LDL receptor or its gene.
This book is an indispensable guide for biologists, physiologists, and clinicians who are interested in the epidemiological field of cholesterol and heart attacks.
Foreword: Simplifying Cholesterol Metabolism
1. The LDL Receptor in Perspective
2. Cholesterol in Animal Tissues
I. Functions and Distribution
II. Sources of Cholesterol in Different Tissues
III. Measurement of Whole-Body Synthesis of Cholesterol
3. HMG-CoA Reductase
I. The Rate-Limiting Step in Cholesterol Biosynthesis
II. Composition, Structure, and Orientation
III. The HMG-CoA Reductase Gene and Its mRNA
IV. Somatic-Cell Mutants in the Study of Cholesterol Metabolism
V. The Regulation of HMG-CoA Reductase
4. Acyl-CoA: Cholesterol Acyltransferase
I. Biological Functions
II. Properties and Methods of Assay
III. ACAT and the Metabolism of Intracellular Cholesteryl Esters
IV. Regulation of ACAT
5. LDL: Physical and Chemical Characteristics
I. Composition and Physical Characteristics
III. Heterogeneity and Genetic Polymorphism
6. Apolipoprotein Β (apoB)
I. LDL ApoB: Definition and Some Properties
II. ApoB Species in Human Plasma
III. Composition and Structure of ApoB-100
IV. Lp(a): A Lipoprotein Containing ApoB-100
V. The LDL-Receptor-Binding Site on ApoB
VI. The ApoB Gene and Its mRNA
VII. Polymorphism in the Human ApoB Gene
VIII. Polymorphism in the ApoB Gene in Animals
IX. ApoB (Arg3500→Gln): A Rare Variant
X. Mutations Causing Absence or Deficiency of Plasma ApoB
7. LDL: Origin and Metabolism
I. The Production of LDL
II. LDL Catabolism In Vivo
8. The LDL Receptor: Biochemistry and Cell Biology
I. Historical Background
II. Surface Binding and Intracellular Degradation of LDL
III. LDL Receptors in Nonfibroblast Cells
IV. Effects of Growth Factors and Hormones In Vitro
9. The LDL Receptor: Structure, Biosynthesis, and Molecular Genetics
I. The Route to Isolation of the Human Receptor and Its Gene
II. The Normal LDL Receptor
III. The LDL-Receptor Gene and Its Message
IV. Regulation of Expression of the Receptor Gene
V. Natural Mutations at the Receptor Locus
VI. Somatic-Cell Mutations
VII. Polymorphism in the LDL-Receptor Gene
VIII. Evolutionary Aspects of the Receptor Gene
10. Normal and Defective LDL-Receptor Function In Vivo
II. Comparison between LDL-Receptor Function In Vitro and In Vivo
III. Familial Hypercholesterolemia: A Consequence of LDL-Receptor Deficiency
IV. The WHHL Rabbit
Appendix A: Abbreviations for Amino Acids
Appendix B: Abbreviations for Nucleotide Bases
- No. of pages:
- © Academic Press 1990
- 28th June 1990
- Academic Press
- eBook ISBN:
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