Table Of Content

Lehninger PRINCIPLES OF BIOCHEMISTRY Fourth Edition David L. Nelson (University of Wisconsin–Madison) Michael M. Cox (University of Wisconsin–Madison) New to This Edition Every chapter fully updated: Including coverage of the human genome and genomics integrated throughout, and key developments since the publication of the third edition, such as the structure of the ribosome. New treatment of metabolic regulation: NEW Chapter 15 gives students the most up-to- date picture of how cells maintain biochemical homeostasis by including modern concepts in metabolic regulation. New, earlier coverage of DNA-based information technologies (Chapter 9): Shows how advances in DNA technology are revolutionizing medicine and biotechnology; examines cloning and genetic engineering, as well as the implications of human gene therapy. Glycolysis and gluconeogenesis now presented in a single chapter (Chapter 14). Redesigned and Expanded Treatment of Enzyme Mechanisms: NEW Mechanism Figures designed to lead students through these reactions step by step. The first reaction mechanism treated in the book, chymotrypsin, presents a refresher on how to follow and understand reaction mechanism diagrams. Twelve new mechanisms have been added, including lysozyme. New Medical and Life Sciences Examples: This edition adds boxed features of biochemical methods, medical applications, and the history of biochemistry, adding to those already present of medicine, biotechnology, and other aspects of daily life. Web site at: www.whfreeman.com/lehninger4e For students: Biochemistry in 3D molecular structure tutorials: Self-paced, interactive tutorials based on the Chemscape Chime molecular visualization browser plug-in. Chime tutorial archive provides links to some of the best Chime tutorials available on the Web. Online support for the Biochemistry on the Internet problems in the textbook. Flashcards on key terms from the text. Online quizzing for each chapter, a new way for students to review material and prepare for exams. Animated mechanisms viewed in Flash or PowerPoint formats give students and instructors a way to visualize mechanisms in a two-dimensional format. Living Graphs illustrate graphed material featured in the text. Bonus Material from Lehninger, Principles of Biochemistry, Third Edition: fundamental Chapters 1, 2, and 3 from the third edition that instructors find useful for their students as a basis for their biochemistry studies. For instructors: All the figures from the book optimized for projection, available in PowerPoint and JPEG format; also available on the IRCD (see below). CHIME Student CD, 0-7167-7049-0 This CD allows students to view Chime tutorials without having to install either the older version of Netscape or the Chime plug-in. Available packaged with Lehninger for free,this optional Student CD-ROM also includes the animated mechanisms and living graphs from the Web site. Instructor's Resource CD-ROM with Test Bank, 0-7167-5953-5 All the images and tables from the text in JPEG and PowerPoint formats, optimized for projection with enhanced colors, higher resolution and enlarged fonts for easy reading in the lecture hall. Animated enzyme mechanisms. Living Graphs Test Bank organized by chapter in the form of .pdf files and editable Word files. Supplements For Instructors Printed Test Bank, Terry Platt and Eugene Barber, University of Rochester Medical Cente), David L. Nelson and Brook Chase Soltvedt, University of Wisconsin-Madison, 0-7167-5952-7 The new Test Bank contains 25% new multiple-choice and short-answer problems and solutions with approximately 50 problems and solutions per chapter. Each problem is keyed to the corresponding chapter of the text and rated by level of difficulty. Overhead Transparency Set, 0-7167-5956-X The full-color transparency set contains 150 key illustrations from the text, with enlarged labels that project more clearly for lecture hall presentation. For Students The Absolute, Ultimate Guide to Lehninger, Principles of Biochemistry, Fourth Edition: Study Guide and Solutions Manual, Marcy Osgood, University of New Mexico, and Karen Ocorr, University of California, San Diego, 0-7167-5955-1 The Absolute, Ultimate Guide combines an innovative study guide with a reliable solutions manual in one convenient volume. A poster-size Cellular Metabolic Map is packaged with the Guide, on which students can draw the reactions and pathways of metabolism in their proper compartments within the cell. Exploring Genomes, Paul G. Young (Queens University), 0-7167-5738-2 Used in conjunction with the online tutorials found at www.whfreeman.com/young, Exploring Genomes guides students through live searches and analyses on the most commonly used National Center for Biotechnology Information (NCBI) database. Lecture Notebook, 0-7167-5954-3 Bound volume of black and white reproductions of all the text's line art and tables, allowing students to concentrate on the lecture instead of copying illustrations. Also includes: Essential reaction equations and mathematical equations with identifying labels Complete pathway diagrams and individual reaction diagrams for all metabolic pathways in the book References that key the material in the text to the CD-ROM and Web Site Lehninger Principles of Biochemistry Fourth Edition David L. Nelson (U. of Wisconsin–Madison) Michael M. Cox (U. of Wisconsin–Madison) 1. The Foundations of Biochemistry 1.1 Cellular Foundations 1.2 Chemical Foundations 1.3 Physical Foundations 1.4 Genetic Foundations 1.5 Evolutionary Foundations Distilled and reorganized from Chapters 1–3 of the previous edition, this overview provides a refresher on the cellular, chemical, physical, genetic, and evolutionary background to biochemistry, while orienting students toward what is unique about biochemistry. PART I. STRUCTURE AND CATALYSIS 2. Water 2.1 Weak Interactions in Aqueous Systems 2.2 Ionization of Water, Weak Acids, and Weak Bases 2.3 Buffering against pH Changes in Biological Systems 2.4 Water as a Reactant 2.5 The Fitness of the Aqueous Environment for Living Organisms Includes new coverage of the concept of protein-bound water, illustrated with molecular graphics. 3. Amino Acids, Peptides, and Proteins 3.1 Amino Acids 3.2 Peptides and Proteins 3.3 Working with Proteins 3.4 The Covalent Structure of Proteins 3.5 Protein Sequences and Evolution Adds important new material on genomics and proteomics and their implications for the study of protein structure, function, and evolution. 4. The Three-Dimensional Structure of Proteins 4.1 Overview of Protein Structure 4.2 Protein Secondary Structure 4.3 Protein Tertiary and Quaternary Structures 4.4 Protein Denaturation and Folding Adds a new box on scurvy. 5. Protein Function 5.1 Reversible Binding of a Protein to a Ligand: Oxygen-Binding Proteins 5.2 Complementary Interactions between Proteins and Ligands: The Immune System and Immunoglobulins 5.3 Protein Interactions Modulated by Chemical Energy: Actin, Myosin, and Molecular Motors Adds a new box on carbon monoxide poisoning 6. Enzymes 6.1 An Introduction to Enzymes 6.2 How Enzymes Work 6.3 Enzyme Kinetics as An Approach to Understanding Mechanism 6.4 Examples of Enzymatic Reactions 6.5 Regulatory Enzymes Offers a revised presentation of the mechanism of chymotrypsin (the first reaction mechanism in the book), featuring a two-page figure that takes students through this particular mechanism, while serving as a step-by-step guide to interpreting any reaction mechanism Features new coverage of the mechanism for lysozyme including the controversial aspects of the mechanism and currently favored resolution based on work published in 2001. 7. Carbohydrates and Glycobiology 7.1 Monosaccharides and Disaccharides 7.2 Polysaccharides 7.3 Glycoconjugates: Proteoglycans, Glycoproteins, and Glycolipids 7.4 Carbohydrates as Informational Molecules: The Sugar Code 7.5 Working with Carbohydrates Includes new section on polysaccharide conformations. A striking new discussion of the "sugar code" looks at polysaccharides as informational molecules, with detailed discussions of lectins, selectins, and oligosaccharide-bearing hormones. Features new material on structural heteropolysaccharides and proteoglycans Covers recent techniques for carbohydrate analysis. 8. Nucleotides and Nucleic Acids 8.1 Some Basics 8.2 Nucleic Acid Structure 8.3 Nucleic Acid Chemistry 8.4 Other Functions of Nucleotides 9. DNA-Based Information Technologies 9.1 DNA Cloning: The Basics 9.2 From Genes to Genomes 9.3 From Genomes to Proteomes 9.4 Genome Alterations and New Products of Biotechnology Introduces the human genome. Biochemical insights derived from the human genome are integrated throughout the text. Tracking the emergence of genomics and proteomics, this chapter establishes DNA technology as a core topic and a path to understanding metabolism, signaling, and other topics covered in the middle chapters of this edition. Includes up-to-date coverage of microarrays, protein chips, comparative genomics, and techniques in cloning and analysis. 10. Lipids 10.1 Storage Lipids 10.2 Structural Lipids in Membranes 10.3 Lipids as Signals, Cofactors, and Pigments 10.4 Working with Lipids Integrates new topics specific to chloroplasts and archaebacteria Adds material on lipids as signal molecules. 11. Biological Membranes and Transport 11.1 The Composition and Architecture of Membranes 11.2 Membrane Dynamics 11.3 Solute Transport across Membranes Includes a description of membrane rafts and microdomains within membranes, and a new box on the use of atomic force microscopy to visualize them. Looks at the role of caveolins in the formation of membrane caveolae Covers the investigation of hop diffusion of membrane lipids using FRAP (fluorescence recovery after photobleaching) Adds new details to the discussion of the mechanism of Ca2- ATPase (SERCA pump), revealed by the recently available high-resolution view of its structure Explores new facets of the mechanisms of the K+ selectivity filter, brought to light by recent high-resolution structures of the K+ channel Illuminates the structure, role, and mechanism of aquaporins with important new details Describes ABC transporters, with particular attention to the multidrug transporter (MDR1) Includes the newly solved structure of the lactose transporter of E. coli. 12. Biosignaling 12.1 Molecular Mechanisms of Signal Transduction 12.2 Gated Ion Channels 12.3 Receptor Enzymes 12.4 G Protein-Coupled Receptors and Second Messengers 12.5 Multivalent Scaffold Proteins and Membrane Rafts 12.6 Signaling in Microorganisms and Plants 12.7 Sensory Transduction in Vision, Olfaction, and Gustation 12.8 Regulation of Transcription by Steroid Hormones 12.9 Regulation of the Cell Cycle by Protein Kinases 12.10 Oncogenes, Tumor Suppressor Genes, and Programmed Cell Death Updates the previous edition's groundbreaking chapter to chart the continuing rapid development of signaling research Includes discussion on general mechanisms for activation of protein kinases in cascades Now covers the roles of membrane rafts and caveolae in signaling pathways, including the activities of AKAPs (A Kinase Anchoring Proteins) and other scaffold proteins Examines the nature and conservation of families of multivalent protein binding modules, which combine to create many discrete signaling pathways Adds a new discussion of signaling in plants and bacteria, with comparison to mammalian signaling pathways Features a new box on visualizing biochemistry with fluorescence resonance energy transfer (FRET) with green fluorescent protein (GFP) PART II: BIOENERGETICS AND METABOLISM 13. Principles of Bioenergetics 13.1 Bioenergetics and Thermodynamics 13.2 Phosphoryl Group Transfers and ATP 13.3 Biological Oxidation-Reduction Reactions Examines the increasing awareness of the multiple roles of polyphosphate Adds a new discussion of niacin deficiency and pellagra. 14. Glycolysis, Gluconeogenesis, and the Pentose Phosphate Pathway 14.1 Glycolysis 14.2 Feeder Pathways for Glycolysis 14.3 Fates of Pyruvate under Anaerobic Conditions: Fermentation 14.4 Gluconeogenesis 14.5 Pentose Phosphate Pathway of Glucose Oxidation Now covers gluconeogenesis immediately after glycolysis, discussing their relatedness, differences, and coordination and setting up the completely new chapter on metabolic regulation that follows Adds coverage of the mechanisms of phosphohexose isomerase and aldolase Revises the presentation of the mechanism of glyceraldehyde 3-phosphate dehydrogenase. New Chapter 15. Principles of Metabolic Regulation, Illustrated with Glucose and Glycogen Metabolism 15.1 The Metabolism of Glycogen in Animals 15.2 Regulation of Metabolic Pathways 15.3 Coordinated Regulation of Glycolysis and Gluconeogenesis 15.4 Coordinated Regulation of Glycogen Synthesis and Breakdown 15.5 Analysis of Metabolic Control Brings together the concepts and principles of metabolic regulation in one chapter Concludes with the latest conceptual approaches to the regulation of metabolism, including metabolic control analysis and contemporary methods for studying and predicting the flux through metabolic pathways 16. The Citric Acid Cycle 16.1 Production of Acetyl-CoA (Activated Acetate) 16.2 Reactions of the Citric Acid Cycle 16.3 Regulation of the Citric Acid Cycle 16.4 The Glyoxylate Cycle Expands and updates the presentation of the mechanism for pyruvate carboxylase. Adds coverage of the mechanisms of isocitrate dehydrogenase and citrate synthase. 17. Fatty Acid Catabolism 17.1 Digestion, Mobilization, and Transport of Fats 17.2 Oxidation of Fatty Acids 17.3 Ketone Bodies Updates coverage of trifunctional protein New section on the role of perilipin phosphorylation in the control of fat mobilization New discussion of the role of acetyl-CoA in the integration of fatty acid oxidation and synthesis Updates coverage of the medical consequences of genetic defects in fatty acyl–CoA dehydrogenases Takes a fresh look at medical issues related to peroxisomes 18. Amino Acid Oxidation and the Production of Urea 18.1 Metabolic Fates of Amino Groups 18.2 Nitrogen Excretion and the Urea Cycle 18.3 Pathways of Amino Acid Degradation Integrates the latest on regulation of reactions throughout the chapter, with new material on genetic defects in urea cycle enzymes, and updated information on the regulatory function of N-acetylglutamate synthase. Reorganizes coverage of amino acid degradation to focus on the big picture Adds new material on the relative importance of several degradative pathways Includes a new description of the interplay of the pyridoxal phosphate and tetrahydrofolate cofactors in serine and glycine metabolism 19. Oxidative Phosphorylation and Photophosphorylation Oxidative Phosporylation 19.1 Electron-Transfer Reactions in Mitochondria 19.2 ATP Synthesis 19.3 Regulation of Oxidative Phosphorylation 19.4 Mitochondrial Genes: Their Origin and the Effects of Mutations 19.5 The Role of Mitochondria in Apoptosis and Oxidative Stress Photosynthesis: Harvesting Light Energy 19.6 General Features of Photophosphorylation 19.7 Light Absorption 19.8 The Central Photochemical Event: Light-Driven Electron Flow 19.9 ATP Synthesis by Photophosphorylation Adds a prominent new section on the roles of mitochondria in apoptosis and oxidative stress Now covers the role of IF1 in the inhibition of ATP synthase during ischemia Includes revelatory details on the light-dependent pathways of electron transfer in photosynthesis, based on newly available molecular structures 20. Carbohydrate Biosynthesis in Plants and Bacteria 20.1 Photosynthetic Carbohydrate Synthesis 20.2 Photorespiration and the C and CAM Pathways 4 20.3 Biosynthesis of Starch and Sucrose 20.4 Synthesis of Cell Wall Polysaccharides: Plant Cellulose and Bacterial Peptidoglycan 20.5 Integration of Carbohydrate Metabolism in the Plant Cell Reorganizes the coverage of photosynthesis and the C and CAM pathways 4 Adds a major new section on the synthesis of cellulose and bacterial peptidoglycan 21. Lipid Biosynthesis 21.1 Biosynthesis of Fatty Acids and Eicosanoids 21.2 Biosynthesis of Triacylglycerols 21.3 Biosynthesis of Membrane Phospholipids 21.4 Biosynthesis of Cholesterol, Steroids, and Isoprenoids Features an important new section on glyceroneogenesis and the triacylglycerol cycle between adipose tissue and liver, including their roles in fatty acid metabolism (especially during starvation) and the emergence of thiazolidinediones as regulators of glyceroneogenesis in the treatment of type II diabetes Includes a timely new discussion on the regulation of cholesterol metabolism at the genetic level, with consideration of sterol regulatory element-binding proteins (SREBPs). 22. Biosynthesis of Amino Acids, Nucleotides, and Related Molecules 22.1 Overview of Nitrogen Metabolism 22.2 Biosynthesis of Amino Acids 22.3 Molecules Derived from Amino Acids 22.4 Biosynthesis and Degradation of Nucleotides Adds material on the regulation of nitrogen metabolism at the level of transcription Significantly expands coverage of synthesis and degradation of heme 23. Integration and Hormonal Regulation of Mammalian Metabolism 23.1 Tissue-Specific Metabolism: The Division of Labor 23.2 Hormonal Regulation of Fuel Metabolism 23.3 Long Term Regulation of Body Mass 23.4 Hormones: Diverse Structures for Diverse Functions Reorganized presentation leads students through the complex interactions of integrated metabolism step by step Features extensively revised coverage of insulin and glucagon metabolism that includes the integration of carbohydrate and fat metabolism New discussion of the role of AMP-dependent protein kinase in metabolic integration Updates coverage of the fast-moving field of obesity, regulation of body mass, and the leptin and adiponectin regulatory systems Adds a discussion of Ghrelin and PYY3-36 as regulators of short-term eating behavior Covers the effects of diet on the regulation of gene expression, considering the role of peroxisome proliferator-activated receptors (PPARs) PART III. INFORMATION PATHWAYS 24. Genes and Chromosomes 24.1 Chromosomal Elements 24.2 DNA Supercoiling 24.3 The Structure of Chromosomes