Preview Lehninger Principles of Biochemistry 8th edition by David L. Nelson, Michael M. Cox, Aaron A. Hoskins (2021)

Preview Lehninger Principles of Biochemistry 8th edition by David L. Nelson, Michael M. Cox, Aaron A. Hoskins (2021) Preview Lehninger Principles of Biochemistry 8th edition by David L. Nelson, Michael M. Cox, Aaron A. Hoskins (2021) Preview Lehninger Principles of Biochemistry 8th edition by David L. Nelson, Michael M. Cox, Aaron A. Hoskins (2021) Preview Lehninger Principles of Biochemistry 8th edition by David L. Nelson, Michael M. Cox, Aaron A. Hoskins (2021)

Lehninger Principles of Biochemistry Lehninger Principles of Biochemistry EIGHTH EDITION David L Nelson Professor Emeritus of Biochemistry University of Wisconsin–Madison Michael M Cox Professor of Biochemistry University of Wisconsin–Madison Aaron A Hoskins Associate Professor of Biochemistry University of Wisconsin–Madison Senior Vice President, STEM: Daryl Fox Executive Program Director: Sandra Lindelof Program Manager, Biochemistry: Elizabeth Simmons Senior Marketing Manager: Maureen Rachford Executive Content Development Manager, STEM: Debbie Hardin Development Editor: Catherine Murphy Executive Project Manager, Content, STEM: Katrina Mangold Editorial Project Manager: Karen Misler Director of Content, Life and Earth Sciences: Jennifer Driscoll Hollis Executive Media Editor: Amy Thorne Media Editors: Cassandra Korsvik, Kelsey Hughes Editorial Assistant: Nathan Livingston Marketing Assistant: Morgan Psiuk Director of Content Management Enhancement: Tracey Kuehn Senior Managing Editor: Lisa Kinne Senior Content Project Manager: Vivien Weiss Senior Workflow Project Manager: Paul W Rohloff Production Supervisor: Robert Cherry Director of Design, Content Management: Diana Blume Design Services Manager: Natasha Wolfe Cover Designer: John Callahan Text Designer: Maureen McCutcheon Art Managers: Janice Donnola, Matthew McAdams Illustrations: Emiko Paul, H Adam Steinberg Director of Digital Production: Keri deManigold Media Project Manager: Brian Nobile Permissions Manager: Michael McCarty Media Permissions Manager: Christine Buese Photo Researcher: Jennifer Atkins Composition: Lumina Datamatics, Inc Cover Image, Title Page, and Part Openers: Janet Iwasa, University of Utah Library of Congress Control Number: 2020942138 ISBN-13: 978-1-319-32234-2 (epub) © 2021, 2017, 2013, 2008 by W H Freeman and Company All rights reserved 1    2    3    4    5    6          25    24    23    22    21    20 Macmillan Learning One New York Plaza Suite 4600 New York, NY 10004-1562 www.macmillanlearning.com In 1946, William Freeman founded W H Freeman and Company and published Linus Pauling’s General Chemistry, which revolutionized the chemistry curriculum and established the prototype for a Freeman text W H Freeman quickly became a publishing house where leading researchers can make significant contributions to mathematics and science In 1996, W H Freeman joined Macmillan and we have since proudly continued the legacy of providing revolutionary, quality educational tools for teaching and learning in STEM To Our Teachers Paul R Burton Albert Finholt Jeff Gelles William P Jencks Eugene P Kennedy Homer Knoss Arthur Kornberg I Robert Lehman Andy LiWang Patti LiWang Melissa J Moore Douglas A Nelson Wesley A Pearson David E Sheppard JoAnne Stubbe Harold B White About the Authors David L Nelson, born in Fairmont, Minnesota, received his BS in chemistry and biology from St Olaf College in 1964, and earned his PhD in biochemistry at Stanford Medical School, under Arthur Kornberg He was a postdoctoral fellow at the Harvard Medical School with Eugene P Kennedy, who was one of Albert Lehninger’s first graduate students Nelson joined the faculty of the University of Wisconsin–Madison in 1971 and became a full professor of biochemistry in 1982 For eight years he was Director of the Center for Biology Education at the University of Wisconsin–Madison He became Professor Emeritus in 2013 Thiazolidinediones Treat Type Diabetes by Increasing Glyceroneogenesis 21.3 Biosynthesis of Membrane Phospholipids Cells Have Two Strategies for Attaching Phospholipid Head Groups Pathways for Phospholipid Biosynthesis Are Interrelated Eukaryotic Membrane Phospholipids Are Subject to Remodeling Plasmalogen Synthesis Requires Formation of an Ether-Linked Fatty Alcohol Sphingolipid and Glycerophospholipid Synthesis Share Precursors and Some Mechanisms Polar Lipids Are Targeted to Specific Cellular Membranes 21.4 Cholesterol, Steroids, and Isoprenoids: Biosynthesis, Regulation, and Transport Cholesterol Is Made from Acetyl-CoA in Four Stages Cholesterol Has Several Fates Cholesterol and Other Lipids Are Carried on Plasma Lipoproteins HDL Carries Out Reverse Cholesterol Transport Cholesteryl Esters Enter Cells by Receptor-Mediated Endocytosis Cholesterol Synthesis and Transport Are Regulated at Several Levels 83 Dysregulation of Cholesterol Metabolism Can Lead to Cardiovascular Disease Reverse Cholesterol Transport by HDL Counters Plaque Formation and Atherosclerosis Steroid Hormones Are Formed by Side-Chain Cleavage and Oxidation of Cholesterol BOX 21-2 The Lipid Hypothesis and the Development of Statins Intermediates in Cholesterol Biosynthesis Have Many Alternative Fates 22 Biosynthesis of Amino Acids, Nucleotides, and Related Molecules 22.1 Overview of Nitrogen Metabolism A Global Nitrogen Cycling Network Maintains a Pool of Biologically Available Nitrogen Nitrogen Is Fixed by Enzymes of the Nitrogenase Complex BOX 22-1 Unusual Lifestyles of the Obscure but Abundant Ammonia Is Incorporated into Biomolecules through Glutamate and Glutamine Glutamine Synthetase Is a Primary Regulatory Point in Nitrogen Metabolism Several Classes of Reactions Play Special Roles in the Biosynthesis of Amino Acids and Nucleotides 22.2 Biosynthesis of Amino Acids 84 Organisms Vary Greatly in Their Ability to Synthesize the 20 Common Amino Acids α-Ketoglutarate Gives Rise to Glutamate, Glutamine, Proline, and Arginine Serine, Glycine, and Cysteine Are Derived from 3Phosphoglycerate Three Nonessential and Six Essential Amino Acids Are Synthesized from Oxaloacetate and Pyruvate Chorismate Is a Key Intermediate in the Synthesis of Tryptophan, Phenylalanine, and Tyrosine Histidine Biosynthesis Uses Precursors of Purine Biosynthesis Amino Acid Biosynthesis Is under Allosteric Regulation 22.3 Molecules Derived from Amino Acids Glycine Is a Precursor of Porphyrins Heme Degradation Has Multiple Functions BOX 22-2 On Kings and Vampires Amino Acids Are Precursors of Creatine and Glutathione d-Amino Acids Are Found Primarily in Bacteria Aromatic Amino Acids Are Precursors of Many Plant Substances Biological Amines Are Products of Amino Acid Decarboxylation Arginine Is the Precursor for Biological Synthesis of Nitric Oxide 85 22.4 Biosynthesis and Degradation of Nucleotides De Novo Purine Nucleotide Synthesis Begins with PRPP Purine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition Pyrimidine Nucleotides Are Made from Aspartate, PRPP, and Carbamoyl Phosphate Pyrimidine Nucleotide Biosynthesis Is Regulated by Feedback Inhibition Nucleoside Monophosphates Are Converted to Nucleoside Triphosphates Ribonucleotides Are the Precursors of Deoxyribonucleotides Thymidylate Is Derived from dCDP and dUMP Degradation of Purines and Pyrimidines Produces Uric Acid and Urea, Respectively Purine and Pyrimidine Bases Are Recycled by Salvage Pathways Excess Uric Acid Causes Gout Many Chemotherapeutic Agents Target Enzymes in Nucleotide Biosynthetic Pathways 23 Hormonal Regulation and Integration of Mammalian Metabolism 23.1 Hormone Structure and Action Hormones Act through Specific High-Affinity Cellular Receptors Hormones Are Chemically Diverse 86 Some Hormones Are Released by a “Top-Down” Hierarchy of Neuronal and Hormonal Signals “Bottom-Up” Hormonal Systems Send Signals Back to the Brain and to Other Tissues 23.2 Tissue-Specific Metabolism The Liver Processes and Distributes Nutrients Adipose Tissues Store and Supply Fatty Acids Brown and Beige Adipose Tissues Are Thermogenic Muscles Use ATP for Mechanical Work The Brain Uses Energy for Transmission of Electrical Impulses BOX 23-1 Creatine and Creatine Kinase: Invaluable Diagnostic Aids and the Muscle Builder’s Friends Blood Carries Oxygen, Metabolites, and Hormones 23.3 Hormonal Regulation of Fuel Metabolism Insulin Counters High Blood Glucose in the Well-Fed State Pancreatic β Cells Secrete Insulin in Response to Changes in Blood Glucose Glucagon Counters Low Blood Glucose During Fasting and Starvation, Metabolism Shi s to Provide Fuel for the Brain Epinephrine Signals Impending Activity Cortisol Signals Stress, Including Low Blood Glucose 23.4 Obesity and the Regulation of Body Mass Adipose Tissue Has Important Endocrine Functions 87 Leptin Stimulates Production of Anorexigenic Peptide Hormones Leptin Triggers a Signaling Cascade That Regulates Gene Expression Adiponectin Acts through AMPK to Increase Insulin Sensitivity AMPK Coordinates Catabolism and Anabolism in Response to Metabolic Stress The mTORC1 Pathway Coordinates Cell Growth with the Supply of Nutrients and Energy Diet Regulates the Expression of Genes Central to Maintaining Body Mass Short-Term Eating Behavior Is Influenced by Ghrelin, , and Cannabinoids Microbial Symbionts in the Gut Influence Energy Metabolism and Adipogenesis 23.5 Diabetes Mellitus Diabetes Mellitus Arises from Defects in Insulin Production or Action BOX 23-2 The Arduous Path to Purified Insulin Carboxylic Acids (Ketone Bodies) Accumulate in the Blood of Those with Untreated Diabetes In Type Diabetes the Tissues Become Insensitive to Insulin Type Diabetes Is Managed with Diet, Exercise, Medication, and Surgery III INFORMATION PATHWAYS 88 24 Genes and Chromosomes 24.1 Chromosomal Elements Genes Are Segments of DNA That Code for Polypeptide Chains and RNAs DNA Molecules Are Much Longer than the Cellular or Viral Packages That Contain Them Eukaryotic Genes and Chromosomes Are Very Complex 24.2 DNA Supercoiling Most Cellular DNA Is Underwound DNA Underwinding Is Defined by Topological Linking Number Topoisomerases Catalyze Changes in the Linking Number of DNA DNA Compaction Requires a Special Form of Supercoiling 24.3 The Structure of Chromosomes Chromatin Consists of DNA, Proteins, and RNA Histones Are Small, Basic Proteins Nucleosomes Are the Fundamental Organizational Units of Chromatin Nucleosomes Are Packed into Highly Condensed Chromosome Structures BOX 24-1 Epigenetics, Nucleosome Structure, and Histone Variants BOX 24-2 Curing Disease by Inhibiting Topoisomerases 89 BOX 24-3 X Chromosome Inactivation by an lncRNA: Preventing Too Much of a Good (or Bad) Thing Condensed Chromosome Structures Are Maintained by SMC Proteins Bacterial DNA Is Also Highly Organized 25 DNA Metabolism 25.1 DNA Replication DNA Replication Follows a Set of Fundamental Rules DNA Is Degraded by Nucleases DNA Is Synthesized by DNA Polymerases Replication Is Very Accurate E coli Has at Least Five DNA Polymerases DNA Replication Requires Many Enzymes and Protein Factors Replication of the E coli Chromosome Proceeds in Stages Replication in Eukaryotic Cells Is Similar but More Complex Viral DNA Polymerases Provide Targets for Antiviral Therapy 25.2 DNA Repair Mutations Are Linked to Cancer All Cells Have Multiple DNA Repair Systems BOX 25-1 DNA Repair and Cancer 90 The Interaction of Replication Forks with DNA Damage Can Lead to Error-Prone Translesion DNA Synthesis 25.3 DNA Recombination Bacterial Homologous Recombination Is a DNA Repair Function Eukaryotic Homologous Recombination Is Required for Proper Chromosome Segregation during Meiosis BOX 25-2 Why Proper Segregation of Chromosomes Matters Some Double-Strand Breaks Are Repaired by Nonhomologous End Joining BOX 25-3 How a DNA Strand Break Gets Attention Site-Specific Recombination Results in Precise DNA Rearrangements Transposable Genetic Elements Move from One Location to Another Immunoglobulin Genes Assemble by Recombination 26 RNA Metabolism 26.1 DNA-Dependent Synthesis of RNA RNA Is Synthesized by RNA Polymerases RNA Synthesis Begins at Promoters BOX 26-1 RNA Polymerase Leaves Its Footprint on a Promoter Transcription Is Regulated at Several Levels Specific Sequences Signal Termination of RNA Synthesis 91 Eukaryotic Cells Have Three Kinds of Nuclear RNA Polymerases RNA Polymerase II Requires Many Other Protein Factors for Its Activity RNA Polymerases Are Drug Targets 26.2 RNA Processing Eukaryotic mRNAs Are Capped at the End ′ Both Introns and Exons Are Transcribed from DNA into RNA RNA Catalyzes the Splicing of Introns In Eukaryotes the Spliceosome Carries out Nuclear pre-mRNA Splicing Proteins Catalyze Splicing of tRNAs Eukaryotic mRNAs Have a Distinctive End ′ Structure A Gene Can Give Rise to Multiple Products by Differential RNA Processing BOX 26-2 Alternative Splicing and Spinal Muscular Atrophy Ribosomal RNAs and tRNAs Also Undergo Processing Special-Function RNAs Undergo Several Types of Processing Cellular mRNAs Are Degraded at Different Rates 26.3 RNA-Dependent Synthesis of RNA and DNA Reverse Transcriptase Produces DNA from Viral RNA Some Retroviruses Cause Cancer and AIDS 92 Many Transposons, Retroviruses, and Introns May Have a Common Evolutionary Origin BOX 26-3 Fighting AIDS with Inhibitors of HIV Reverse Transcriptase Telomerase Is a Specialized Reverse Transcriptase Some RNAs Are Replicated by RNA-Dependent RNA Polymerase RNA-Dependent RNA Polymerases Share a Common Structural Fold 26.4 Catalytic RNAs and the RNA World Hypothesis Ribozymes Share Features with Protein Enzymes Ribozymes Participate in a Variety of Biological Processes Ribozymes Provide Clues to the Origin of Life in an RNA World BOX 26-4 The SELEX Method for Generating RNA Polymers with New Functions 27 Protein Metabolism 27.1 The Genetic Code The Genetic Code Was Cracked Using Artificial mRNA Templates BOX 27-1 Exceptions That Prove the Rule: Natural Variations in the Genetic Code Wobble Allows Some tRNAs to Recognize More than One Codon The Genetic Code Is Mutation-Resistant 93 Translational Frameshi ing Affects How the Code Is Read Some mRNAs Are Edited before Translation 27.2 Protein Synthesis The Ribosome Is a Complex Supramolecular Machine Transfer RNAs Have Characteristic Structural Features Stage 1: Aminoacyl-tRNA Synthetases Attach the Correct Amino Acids to Their tRNAs Stage 2: A Specific Amino Acid Initiates Protein Synthesis BOX 27-2 Natural and Unnatural Expansion of the Genetic Code Stage 3: Peptide Bonds Are Formed in the Elongation Stage BOX 27-3 Ribosome Pausing, Arrest, and Rescue Stage 4: Termination of Polypeptide Synthesis Requires a Special Signal Stage 5: Newly Synthesized Polypeptide Chains Undergo Folding and Processing Protein Synthesis Is Inhibited by Many Antibiotics and Toxins 27.3 Protein Targeting and Degradation Posttranslational Modification of Many Eukaryotic Proteins Begins in the Endoplasmic Reticulum Glycosylation Plays a Key Role in Protein Targeting 94 Signal Sequences for Nuclear Transport Are Not Cleaved Bacteria Also Use Signal Sequences for Protein Targeting Cells Import Proteins by Receptor-Mediated Endocytosis Protein Degradation Is Mediated by Specialized Systems in All Cells 28 Regulation of Gene Expression 28.1 The Proteins and RNAs of Gene Regulation RNA Polymerase Binds to DNA at Promoters Transcription Initiation Is Regulated by Proteins and RNAs Many Bacterial Genes Are Clustered and Regulated in Operons The lac Operon Is Subject to Negative Regulation Regulatory Proteins Have Discrete DNA-Binding Domains Regulatory Proteins Also Have Protein-Protein Interaction Domains 28.2 Regulation of Gene Expression in Bacteria The lac Operon Undergoes Positive Regulation Many Genes for Amino Acid Biosynthetic Enzymes Are Regulated by Transcription Attenuation Induction of the SOS Response Requires Destruction of Repressor Proteins 95 Synthesis of Ribosomal Proteins Is Coordinated with rRNA Synthesis The Function of Some mRNAs Is Regulated by Small RNAs in Cis or in Trans Some Genes Are Regulated by Genetic Recombination 28.3 Regulation of Gene Expression in Eukaryotes Transcriptionally Active Chromatin Is Structurally Distinct from Inactive Chromatin Most Eukaryotic Promoters Are Positively Regulated DNA-Binding Activators and Coactivators Facilitate Assembly of the Basal Transcription Factors The Genes of Galactose Metabolism in Yeast Are Subject to Both Positive and Negative Regulation Transcription Activators Have a Modular Structure Eukaryotic Gene Expression Can Be Regulated by Intercellular and Intracellular Signals Regulation Can Result from Phosphorylation of Nuclear Transcription Factors Many Eukaryotic mRNAs Are Subject to Translational Repression Posttranscriptional Gene Silencing Is Mediated by RNA Interference RNA-Mediated Regulation of Gene Expression Takes Many Forms in Eukaryotes Development Is Controlled by Cascades of Regulatory Proteins 96 Stem Cells Have Developmental Potential That Can Be Controlled BOX 28-1 Of Fins, Wings, Beaks, and Things Abbreviated Solutions to Problems Glossary Index Resources 97 ...1 Lehninger Principles of Biochemistry Lehninger Principles of Biochemistry EIGHTH EDITION David L Nelson Professor Emeritus of Biochemistry University of Wisconsin–Madison Michael M Cox Professor... Wisconsin–Madison Michael M Cox Professor of Biochemistry University of Wisconsin–Madison Aaron A Hoskins Associate Professor of Biochemistry University of Wisconsin–Madison Senior Vice President,... Nelson, Michael Cox, and new coauthor Aaron Hoskins have focused this eighth edition around the fundamental principles to help students understand and navigate the most important aspects of biochemistry