Principles of biochemistry (David L. Nelson & Michael M. Cox.)
As we complete our work on this sixth edition of Lehninger Principles of Biochemistry, we are again struck by the remarkable changes in the field of biochemistry that have occurred between editions. The sheer volume of new information from high-throughput DNA sequencing, x-ray crystallography, and the manipulation of genes and gene expression, to cite only three examples, challenges both the seasoned researcher and the first-time biochemistry student. Our goal here is to strike a balance: to include new and exciting research findings without making the book overwhelming for students. The primary criterion for inclusion is that the new finding helps to illustrate an important principle of biochemistry.
The image on our cover, a map of the known metabolic transformations in a mitochondrion, illustrates the richness of factual material now available about biochemical transformations. We can no longer treat metabolic “pathways” as though they occurred in isolation; a single metabolite may be simultaneously part of many pathways in a three-dimensional network of metabolic transformations. Biochemical research focuses more and more upon the interactions among these pathways, the regulation of their interactions at the level of gene and protein, and the effects of regulation upon the activities of a whole cell or organism.
This edition of LPOB reflects these realities. Much of the new material that we have added reflects our increasingly sophisticated understanding of regulatory mechanisms, including those involved in altering the synthesis of enzymes and their degradation, those responsible for the control and timing of DNA synthesis and the cell cycle, and those that integrate the metabolism of carbohydrates, fats, and proteins over time in response to changes in the environment and in different cell types. Even as we strive to incorporate the latest major advances, certain hallmarks of the book remain unchanged.
We continue to emphasize the relevance of biochemistry to the molecular mechanisms of disease, highlighting the special role that biochemistry plays in advancing human health and welfare. A special theme is the metabolic basis of diabetes and the factors that predispose to the disease. This theme is interwoven through many chapters and serves to integrate the discussion of metabolism. We also underscore the importance of evolution to biochemistry. Evolutionary theory is the bedrock upon which all biological sciences rest, and we have not wasted opportunities to highlight its important role in our discipline.
To a significant degree, research progress in biochemistry runs in parallel with the development of better tools and techniques. We have therefore highlighted some of these crucial developments. Chapter 9, DNABased Information Technologies, in particular, has been significantly revised to include the latest advances in genomics and next-generation sequencing.
Finally, we have devoted considerable attention to making the text and the art even more useful to students learning biochemistry for the first time. To those familiar with the book, some of these changes will be obvious as soon as you crack the cover. With every revision of this textbook, we have striven to maintain the qualities that made the original Lehninger text a classic—clear writing, careful explanations of difficult concepts, and insightful communication to students of the ways in which biochemistry is understood and practiced today. The authors have written together for almost 25 years and taught introductory biochemistry together for nearly 30. Our thousands of students at the University of Wisconsin–Madison over those years have been an endless source of ideas about how to present biochemistry more clearly; they have enlightened and inspired us. We hope that this sixth edition of Lehninger will in turn enlighten and inspire current students of biochemistry everywhere, and perhaps lead some of them to love biochemistry as we do.
New Art
The most obvious change to the book is the completely revamped art program. Our goal throughout has been to improve pedagogy, drawing on modern graphic resources to make our subject as clear as humanly possible. Many figures illustrate new topics, and much of the art has been reconceived and modernized in style. Defining features of the new art program include:
Smarter renditions of classic figures are easier to interpret and learn from;
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)
Updated Genomics
Modern genomic techniques have transformed our understanding of biochemistry. In this edition, we have dramatically updated our coverage of genomic methods and their applications. Chapter 9, DNA-Based Information Technologies, has been completely revised to incorporate the latest genomic methods. Many other chapters have been updated to reflect advances gained from these methods. Among the new genomic methods discussed in this edition are: u 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 diseases (Chapter 9)
Forensic genotyping and the use of personalized genomics in medicine (Chapter 9)
New Biochemical Methods
An appreciation of biochemistry often requires an understanding of how biochemical information is obtained. Some of the new methods or updates described in this edition are:
u Modern Sanger protein sequencing and mass spectrometry (Chapter 3)
u Mass spectrometry applied to proteomics, glycomics, lipidomics, and metabolomics (Chapters 3, 7, 10)
u Oligosaccharide microarrays to explore proteinoligosaccharide interactions and the “carbohydrate code” (Chapter 7)
Special Theme: Understanding Metabolism through Obesity and Diabetes Obesity and its medical consequences—cardiovascular disease and diabetes—are fast becoming epidemic in the industrialized world, and we include new material on the biochemical connections between obesity and health throughout this edition. Our focus on diabetes provides an integrating theme throughout the chapters on metabolism and its control, and this will, we hope, inspire some students to find solutions for this disease. Some of the sections and boxes that highlight the interplay of metabolism, obesity, and diabetes are:
Special Theme: Evolution Every time a biochemist studies a developmental pathway in nematodes, identifies key parts of an enzyme active site by determining what parts are conserved between species, or searches for the gene underlying a human genetic disease, he or she is relying on evolutionary theory. Funding agencies support the work in nematodes knowing that the insights will be relevant to humans. The conservation of functional residues in an enzyme active site telegraphs the shared history of every organism on the planet. More often than not, the search for a disease gene is a sophisticated exercise in phylogenetics. Evolution is thus a foundational concept to our discipline. Some of the many sections and boxes that deal with evolution include:
Section 1.5, Evolutionary Foundations, discusses how life may have evolved and recounts some of the early milestones in the evolution of eukaryotic cells
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)
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 what they learned in organic chemistry to help them understand biochemistry. Those same students must also learn a complex language, with conventions that are often unstated. To help students cope with these challenges, we provide the following study aids: 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 students 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, including glycolysis.
