Ebook Principles of biochemistry 4th edition part 1

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 Chemic. Ebook Principles of biochemistry 4th edition part 1

Lehninger Principles of Biochemistry Fourth Edition David L Nelson (U of Wisconsin–Madison) Michael M Cox (U of Wisconsin–Madison) 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 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 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 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 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 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 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 Nucleotides and Nucleic Acids 8.1 Some Basics 8.2 Nucleic Acid Structure 8.3 Nucleic Acid Chemistry 8.4 Other Functions of Nucleotides 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 C4 and CAM Pathways 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 C4 and CAM pathways 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 Integrates important new material on the structure of chromosomes, including the roles of SMC proteins and cohesins, the features of chromosomal DNA, and the organization of genes in DNA 25 DNA Metabolism 25.1 DNA Replication 25.2 DNA Repair 25.3 DNA Recombination Adds a section on the "replication factories" of bacterial DNA Includes latest perspectives on DNA recombination and repair 26 RNA Metabolism 26.1 DNA-Dependent Synthesis of RNA 26.2 RNA Processing 26.3 RNA-Dependent Synthesis of RNA and DNA Updates coverage on mechanisms of mRNA processing Adds a subsection on the 5' cap of eukaryotic mRNAs Adds important new information about the structure of bacterial RNA polymerase and its mechanism of action 27 Protein Metabolism 27.1 The Genetic Code 27.2 Protein Synthesis 27.3 Protein Targeting and Degradation Includes a presentation and analysis of the long-awaited structure of the ribosome-one of the most important updates in this new edition Adds a new box on the evolutionary significance of ribozyme-catalyzed peptide synthesis 28 Regulation of Gene Expression 28.1 Principles of Gene Regulation 28.2 Regulation of Gene Expression in Prokaryotes 28.3 Regulation of Gene Expression in Eukaryotes Adds a new section on RNA interference (RNAi), including the medical potential of gene silencing 8885d_c01_01-46 10/27/03 7:48 AM Page mac76 mac76:385_reb: chapter THE FOUNDATIONS OF BIOCHEMISTRY 1.1 1.2 1.3 1.4 1.5 Cellular Foundations Chemical Foundations 12 Physical Foundations 21 Genetic Foundations 28 Evolutionary Foundations 31 With the cell, biology discovered its atom To characterize life, it was henceforth essential to study the cell and analyze its structure: to single out the common denominators, necessary for the life of every cell; alternatively, to identify differences associated with the performance of special functions Franỗois Jacob, La logique du vivant: une histoire de lhộrộditộ (The Logic of Life: A History of Heredity), 1970 We must, however, acknowledge, as it seems to me, that man with all his noble qualities still bears in his bodily frame the indelible stamp of his lowly origin —Charles Darwin, The Descent of Man, 1871 ifteen to twenty billion years ago, the universe arose as a cataclysmic eruption of hot, energy-rich subatomic particles Within seconds, the simplest elements (hydrogen and helium) were formed As the universe expanded and cooled, material condensed under the influence of gravity to form stars Some stars became enormous and then exploded as supernovae, releasing the energy needed to fuse simpler atomic nuclei into the more complex elements Thus were produced, over billions of years, the Earth itself and the chemical elements found on the Earth today About four billion years ago, F life arose—simple microorganisms with the ability to extract energy from organic compounds or from sunlight, which they used to make a vast array of more complex biomolecules from the simple elements and compounds on the Earth’s surface Biochemistry asks how the remarkable properties of living organisms arise from the thousands of different lifeless biomolecules When these molecules are isolated and examined individually, they conform to all the physical and chemical laws that describe the behavior of inanimate matter—as all the processes occurring in living organisms The study of biochemistry shows how the collections of inanimate molecules that constitute living organisms interact to maintain and perpetuate life animated solely by the physical and chemical laws that govern the nonliving universe Yet organisms possess extraordinary attributes, properties that distinguish them from other collections of matter What are these distinguishing features of living organisms? A high degree of chemical complexity and microscopic organization Thousands of different molecules make up a cell’s intricate internal structures (Fig 1–1a) Each has its characteristic sequence of subunits, its unique three-dimensional structure, and its highly specific selection of binding partners in the cell Systems for extracting, transforming, and using energy from the environment (Fig 1–1b), enabling organisms to build and maintain their intricate structures and to mechanical, chemical, osmotic, and electrical work Inanimate matter tends, rather, to decay toward a more disordered state, to come to equilibrium with its surroundings 8885d_c01_002 11/3/03 Chapter 1:38 PM Page mac76 mac76:385_reb: The Foundations of Biochemistry (a) (b) This is true not only of macroscopic structures, such as leaves and stems or hearts and lungs, but also of microscopic intracellular structures and individual chemical compounds The interplay among the chemical components of a living organism is dynamic; changes in one component cause coordinating or compensating changes in another, with the whole ensemble displaying a character beyond that of its individual parts The collection of molecules carries out a program, the end result of which is reproduction of the program and self-perpetuation of that collection of molecules—in short, life A history of evolutionary change Organisms change their inherited life strategies to survive in new circumstances The result of eons of evolution is an enormous diversity of life forms, superficially very different (Fig 1–2) but fundamentally related through their shared ancestry Despite these common properties, and the fundamental unity of life they reveal, very few generalizations about living organisms are absolutely correct for every organism under every condition; there is enormous diversity The range of habitats in which organisms live, from hot springs to Arctic tundra, from animal intestines to college dormitories, is matched by a correspondingly wide range of specific biochemical adaptations, achieved (c) FIGURE 1–1 Some characteristics of living matter (a) Microscopic complexity and organization are apparent in this colorized thin section of vertebrate muscle tissue, viewed with the electron microscope (b) A prairie falcon acquires nutrients by consuming a smaller bird (c) Biological reproduction occurs with near-perfect fidelity A capacity for precise self-replication and self-assembly (Fig 1–1c) A single bacterial cell placed in a sterile nutrient medium can give rise to a billion identical “daughter” cells in 24 hours Each cell contains thousands of different molecules, some extremely complex; yet each bacterium is a faithful copy of the original, its construction directed entirely from information contained within the genetic material of the original cell Mechanisms for sensing and responding to alterations in their surroundings, constantly adjusting to these changes by adapting their internal chemistry Defined functions for each of their components and regulated interactions among them FIGURE 1–2 Diverse living organisms share common chemical features Birds, beasts, plants, and soil microorganisms share with humans the same basic structural units (cells) and the same kinds of macromolecules (DNA, RNA, proteins) made up of the same kinds of monomeric subunits (nucleotides, amino acids) They utilize the same pathways for synthesis of cellular components, share the same genetic code, and derive from the same evolutionary ancestors Shown here is a detail from “The Garden of Eden,” by Jan van Kessel the Younger (1626–1679) 8885d_c01_003 12/20/03 7:03 AM Page mac76 mac76:385_reb: 1.1 within a common chemical framework For the sake of clarity, in this book we sometimes risk certain generalizations, which, though not perfect, remain useful; we also frequently point out the exceptions that illuminate scientific generalizations Biochemistry describes in molecular terms the structures, mechanisms, and chemical processes shared by all organisms and provides organizing principles that underlie life in all its diverse forms, principles we refer to collectively as the molecular logic of life Although biochemistry provides important insights and practical applications in medicine, agriculture, nutrition, and industry, its ultimate concern is with the wonder of life itself In this introductory chapter, then, we describe (briefly!) the cellular, chemical, physical (thermodynamic), and genetic backgrounds to biochemistry and the overarching principle of evolution—the development over generations of the properties of living cells As you read through the book, you may find it helpful to refer back to this chapter at intervals to refresh your memory of this background material 1.1 Cellular Foundations The unity and diversity of organisms become apparent even at the cellular level The smallest organisms consist of single cells and are microscopic Larger, multicellular organisms contain many different types of cells, which vary in size, shape, and specialized function Despite these obvious differences, all cells of the simplest and most complex organisms share certain fundamental properties, which can be seen at the biochemical level Cells Are the Structural and Functional Units of All Living Organisms Cells of all kinds share certain structural features (Fig 1–3) The plasma membrane defines the periphery of the cell, separating its contents from the surroundings It is composed of lipid and protein molecules that form a thin, tough, pliable, hydrophobic barrier around the cell The membrane is a barrier to the free passage of inorganic ions and most other charged or polar compounds Transport proteins in the plasma membrane allow the passage of certain ions and molecules; receptor proteins transmit signals into the cell; and membrane enzymes participate in some reaction pathways Because the individual lipids and proteins of the plasma membrane are not covalently linked, the entire structure is remarkably flexible, allowing changes in the shape and size of the cell As a cell grows, newly made lipid and protein molecules are inserted into its plasma membrane; cell division produces two cells, each with its own membrane This growth and cell division (fission) occurs without loss of membrane integrity Cellular Foundations Nucleus (eukaryotes) or nucleoid (bacteria) Contains genetic material–DNA and associated proteins Nucleus is membrane-bounded Plasma membrane Tough, flexible lipid bilayer Selectively permeable to polar substances Includes membrane proteins that function in transport, in signal reception, and as enzymes Cytoplasm Aqueous cell contents and suspended particles and organelles centrifuge at 150,000 g Supernatant: cytosol Concentrated solution of enzymes, RNA, monomeric subunits, metabolites, inorganic ions Pellet: particles and organelles Ribosomes, storage granules, mitochondria, chloroplasts, lysosomes, endoplasmic reticulum FIGURE 1–3 The universal features of living cells All cells have a nucleus or nucleoid, a plasma membrane, and cytoplasm The cytosol is defined as that portion of the cytoplasm that remains in the supernatant after centrifugation of a cell extract at 150,000 g for hour The internal volume bounded by the plasma membrane, the cytoplasm (Fig 1–3), is composed of an aqueous solution, the cytosol, and a variety of suspended particles with specific functions The cytosol is a highly concentrated solution containing enzymes and the RNA molecules that encode them; the components (amino acids and nucleotides) from which these macromolecules are assembled; hundreds of small organic molecules called metabolites, intermediates in biosynthetic and degradative pathways; coenzymes, compounds essential to many enzyme-catalyzed reactions; inorganic ions; and ribosomes, small particles (composed of protein and RNA molecules) that are the sites of protein synthesis All cells have, for at least some part of their life, either a nucleus or a nucleoid, in which the genome— ...Lehninger Principles of Biochemistry Fourth Edition David L Nelson (U of Wisconsin–Madison) Michael M Cox (U of Wisconsin–Madison) The Foundations of Biochemistry 1. 1 Cellular Foundations 1. 2 Chemical... chapter THE FOUNDATIONS OF BIOCHEMISTRY 1. 1 1. 2 1. 3 1. 4 1. 5 Cellular Foundations Chemical Foundations 12 Physical Foundations 21 Genetic Foundations 28 Evolutionary Foundations 31 With the cell, biology... 8885d_c 01_ 011 12 /20/03 7:04 AM Page 11 mac76 mac76:385_reb: 1. 1 Level 4: The cell and its organelles Level 3: Supramolecular complexes Level 2: Macromolecules Cellular Foundations 11 Level 1: Monomeric