New Art
The new edition features a dramatically re-invisioned art program that recasts nearly every figure to make them exceptionally strong learning tools:
• New renditions of classic figures are now easier to interpret and learn from
• Figures that pair molecular models with schematic cartoons, generated specifically for this book, now use consistent shapes and color schemes
• Figures of complex processes with numbered, annotated steps now place the descriptive text in the figure itself, not in the caption
• Summary figures help the student to keep the big picture in mind while learning the specifics.
Updated Genomics
Chapter 9, DNA-Based Information Technologies, now incorporates the latest genomic methods. Numerous other chapters have been updated to reflect advances gained from new methods, such as:
• Next generation DNA sequencing, including the Illumina and 454 sequencing methods and platforms (Chapter 9)
• Applications of genomics, including the use of haplotypes to trace human migrations and phylogenetics to locate human genes associated with inherited disease conditions (Chapter 9)
• Forensic genotyping and the use of personalized genomics in medicine (Chapter 9)
New Science
Every chapter has been thoroughly revised and updated to include both the most important advances in biochemistry and information needed in a modern biochemistry text. Among the new and updated topics in this edition are:
• Prebiotic evolution, black smokers, and the RNA world (Chapter 1)
• Intrinsically disordered proteins (Chapter 4)
• Transition state analogs and irreversible inhibition (Chapter 6)
• Blood coagulation pathways in the context of enzymatic regulation (Chapter 6)
• Asymmetric lipid distribution in bilayer (Chapter 11)
• Role of BAR superfamily proteins in membrane curvature (Chapter 11)
• Scaffold proteins (AKAPS and others) and their regulatory roles (Chapter 12)
• Reactive oxygen species as by-products and as signals (Chapter 19)
• Structure and function of the oxygen-evolving metal cluster in PSII (Chapter 19)
• Formation, transport of lipoproteins in mammals, including the roles of SREBP, SCAP, Insig in cholesterol regulation (Chapter 21)
• Integration of carbohydrate and lipid metabolism by PPARs, SREBPs, mTORC1, and LXR (Chapters 21, 23)
• Creatine phosphate and the role of creatine kinase in moving ATP to cytosol (Chapter 23)
• Microbial symbionts in the gut and their influence on energy metabolism and adipogenesis (Chapter 23)
• Nucleosomes: their modification and positioning and higher order chromatin structure (Chapter 24)
• DNA polymerases and homologous recombination (Chapter 25)
• Loading eukaryotic RNA polymerase II (Chapter 26)
• Mutation-resistant nature of the genetic code (Chapter 27)
• Ribosome structure and the initiation of translation in eukaryotes (Chapter 27)
• DNA looping, combinatorial control, chromatin remodeling, and positive regulation in eukaryotes (Chapter 28)
• Regulation of the initiation of transcription in eukaryotes (Chapter 28)
• Steroid-binding nuclear receptors (Chapter 28)
New Biochemical Methods
New methods or updates described in this edition include:
• Modern Sanger protein sequencing and mass spectrometry (Chapter 3)
• Mass spectrometry applied to proteomics, glycomics, lipidomics, and metabolomics (Chapters 3, 7, 10)
• Oligosaccharide microarrays to explore protein-oligosaccharide interactions and the “carbohydrate code” (Chapter 7)
• Modern genomic methods (Chapter 9)
• Genetic engineering of photosynthetic organisms (Chapter 20)
• Use of Positron Emission Tomography (PET) to visualize tumors and brown adipose tissue (Chapter 23)
• Development of bacterial strains with altered genetic codes for site-specific insertion of novel amino acids into proteins (Chapter 27)
New Medical Applications
This icon is used throughout the book to denote material of special medical interest. Many sections explore what we know about the molecular mechanisms of disease. A few of the new or revised medical applications in this edition are:
• Box 4-6, Death by Misfolding: the Prior Diseases (Chapter 4)
• Paganini and Ehlers-Danlos Syndrome (Chapter 4)
• HIV protease inhibitors and how basic enzymatic principles influenced their design (Chapter 6)
• Blood coagulation cascade and hemophilia (Chapter 6)
• Curing African Sleeping Sickness with an enzymatic suicide inhibitor (Chapter 6)
• How researchers locate human genes involved in inherited diseases (Chapter 9)
• Multidrug resistance transporters and their importance in clinical medicine (Chapter 11)
• Multistep progression to colorectal cancer (Chapter 12)
• Cholesterol metabolism, cardiovascular disease, and mechanism of plaque formation in atherosclerosis (Chapter 21)
• P450 and drug interactions (Chapter 21)
• HMG-CoA reductase (Chapter 21) and Box 21–3, The Lipid Hypothesis and the Development of Statins
• Box 24–1, Curing Disease by Inhibiting Topoisomerases, describing the use of topoisomerase inhibitors in the treatment of bacterial infections and cancer, including material on ciprofloxacin (the antibiotic effective for anthrax)
• Stem cells (Chapter 28)
Special Theme: Understanding Metabolism through Obesity and Diabetes
The urgent world health issue of diabetes provides a defining theme for the book’s chapters on metabolism and its control. Sections and boxes highlighting the interplay of metabolism, obesity, and diabetes are:
• Untreated Diabetes Produces Life-Threatening Acidosis (Chapter 2)
• Box 7–1, Blood Glucose Measurements in the Diagnosis and Treatment of Diabetes, introducing hemoglobin glycation and AGEs and their role in the pathology of advanced diabetes
• Glucose Uptake Is Deficient in Type 1 Diabetes Mellitus (Chapter 14)
• Ketone Bodies Are Overproduced in Diabetes and during Starvation (Chapter 17)
• Some Mutations in Mitochondrial Genomes Cause Disease (Chapter 19)
• Diabetes Can Result from Defects in the Mitochondria of Pancreatic Cells (Chapter 19)
• Adipose Tissue Generates Glycerol 3-phosphate by Glyceroneogenesis (Chapter 21)
• Diabetes Mellitus Arises from Defects in Insulin Production or Action (Chapter 23)
• Section 23.4, Obesity and the Regulation of Body Mass, includes a new discussion of the regulatory roles of TORC1 in regulating cell growth
• Section 23.5, Obesity, the Metabolic Syndrome, and Type 2 Diabetes, discusses the role of ectopic lipids and inflammation in the development of insulin resistance, and the management of type 2 diabetes with exercise, diet, and medication
Special Theme: Evolution
Evolution is presented as a foundational principle of biochemistry throughout this edition, including:
• Section 1.5, Evolutionary Foundations, discusses how life may have evolved and canvasses some of the early milestones in the evolution of eukaryotic cells (Chapter 1)
• Genome Sequencing Informs Us about Our Humanity (Chapter 9)
• Genome Comparisons Help Locate Genes Involved in Disease (Chapter 9)
• Genome Sequences Inform Us About Our Past and Provide Opportunities for the Future (Chapter 9)
• BOX 9–3, Getting to Know the Neanderthals (Chapter 9)
• ABC Transporters Use ATP to Drive the Active Transport of a Wide Variety of Substrates (Chapter 11)
• Signaling Systems of Plants Have Some of the Same Components Used by Microbes and Mammals (Chapter 12)
• The β-Oxidation Enzymes of Different Organelles Have Diverged during Evolution (Chapter 17)
• Section 19.10, The Evolution of Oxygenic Photosynthesis
• Mitochondria and Chloroplasts Evolved from Endosymbiotic Bacteria (Chapter 19)
• Photosystems I and II Evolved from Bacterial Photosystems (Chapter 19)
• RNA Synthesis Offers Important Clues to Biochemical Evolution (Chapter 26)
• Box 27–1, Exceptions That Prove the Rule: Natural Variations in the Genetic Code (Chapter 27)
• Box 27–2, From an RNA World to a Protein World (Chapter 27)
• Box 28-1, Of Fins, Wings, Beaks, and Things (Chapter 28)
Lehninger Teaching Hallmarks
Students encountering biochemistry for the first time often have difficulty with two key aspects of the course: approaching quantitative problems and drawing on their previous studies of organic chemistry. Those same students must also learn a complex language, with conventions that are often unstated. As always, Principles of Biochemistry helps students cope with these challenges:
Focus on Chemical Logic
- Section 13.2, Chemical logic and common biochemical reactions, discusses the common biochemical reaction types that underlie all metabolic reactions, helping student to connect organic chemistry with biochemistry.
- NEW chemical logic figures highlight the conservation of mechanism and illustrate patterns that make learning pathways easier. Chemical logic figures are provided for each of the central metabolic pathways: glycolysis (Fig 14-3), citric acid cycle (Fig. 16-7), and fatty acid oxidation (Fig 17-9).
- Mechanism figures feature step-by-step descriptions to help students understand the reaction process. These figures use a consistent set of conventions introduced and explained in detail with the first enzyme mechanism encountered.
Problem-Solving Tools
- In-text Worked Examples take students through some of the most difficult equations step by step. New worked examples appear in Chapters 1, 2, and 19.
- More than 600 end-of-chapter problems (over 75 of them new) give students further opportunity to practice what they have learned.
- Data Analysis Problems (one at the end of each chapter), contributed by Brian White of the University of Massachusetts–Boston, encourage students interpret data from the literature.
Key Conventions
The text highlights clear statements of many assumptions and conventions that students are often expected to assimilate without being told (for example, peptide sequences are written from amino-to carboxyl-terminal end, left to right; nucleotide sequences are written from 5 to 3 end, left to right).