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 MetabolismPreface Acknowledgments 1. The LDL Receptor in Perspective2. Cholesterol in Animal Tissues I. Functions and Distribution II. Sources of Cholesterol in Different Tissues III. Measurement of Whole-Body Synthesis of Cholesterol References3. 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 References4. 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 References 5. LDL: Physical and Chemical Characteristics I. Composition and Physical Characteristics II. Structure III. Heterogeneity and Genetic Polymorphism References 6. Apolipoprotein ¿ (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 References 7. LDL: Origin and Metabolism I. The Production of LDL II. LDL Catabolism In Vivo References 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 References 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 References 10. Normal and Defective LDL-Receptor Function In Vivo I. Introduction II. Comparison between LDL-Receptor Function In Vitro and In Vivo III. Familial Hypercholesterolemia: A Consequence of LDL-Receptor Deficiency IV. The WHHL Rabbit References Glossary Appendix A: Abbreviations for Amino Acids Appendix B: Abbreviations for Nucleotide Bases Index