Preface A,ometeronth施sixth oition of to the molecular mechanisms of disease.highlighting the cing huma sand the f volume of new information from high-throughput DNA This theme is interwoven through many chapters and sequencing.,and the manipulatio serves to integrate the discussion of metabo sm.We alsc bioche stry student.Our goal here is to strike a balance toinclude and exciting ings withou ole in our ais in bic chemistry runs in parallel with the development o pet trate an important principle of bioche ter tools and techniques.We have therefore highlighte in a eoea Based tnfo richness of factual material now available about bio significantly revised to include the latest advances in mation no longe meta genomics and next-generation sequencing single metabolite ay he ,1 art of ma g the text and the art pathways in a thre lim onal network of metaboli dents learing biochemistry for the first time.To thos the book, e of these changes will be With everyre on of this texthook we have striver the effe of regulation upon the activities that made to on the new material that we have added reflects our incre of the ways in which biochemistry is understood and tory mecha today.The authors have ng the ritten together for and their degr dati ble fo ether w300 sands of students at the the control and timing of DNA synthesis and the cell University of Wisconsin-Madison over those years have se tha integrate the meta lism of car peen an endless sou of ideas about to prese changes in the environment and in different cell types inspired us.We hope that this sixth edition ofe majo will in turn enlighten and inspire current students of bio perhaps lea d some of them to New Art The most obvious change to the book is the mped art program. drawing on modemn graphic resources to our subject as clear as humanly possible.Many od in style.Defining features of the new art program include: Smarter renditions of classic figures are easier to interpret and learn from; vi 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 biochem￾istry 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 illus￾trate an important principle of biochemistry. The image on our cover, a map of the known meta￾bolic transformations in a mitochondrion, illustrates the richness of factual material now available about bio￾chemical transformations. We can no longer treat meta￾bolic “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 increas￾ingly sophisticated understanding of regulatory mecha￾nisms, 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 car￾bohydrates, 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 biologi￾cal sciences rest, and we have not wasted opportunities to highlight its important role in our discipline. To a significant degree, research progress in bio￾chemistry runs in parallel with the development of bet￾ter tools and techniques. We have therefore highlighted some of these crucial developments. Chapter 9, DNA￾Based 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 stu￾dents 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 diffi￾cult 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 bio￾chemistry everywhere, and perhaps lead some of them to love biochemistry as we do. Preface 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: u Smarter renditions of classic figures are easier to interpret and learn from; Chaperonins in protein folding FMTOC.indd Page vi 10/10/12 7:30 AM user-F408 /Users/user-F408/Desktop ADP ADP ADP ADP ADP ADP GroES GroEL ADP ADP ADP ADP ADP ADP 7Pi 7Pi 7 7 ATP 7 7 (a) (b) Native protein Slow-folding intermediate or Folding intermediate delivered by Hsp70-ADP Folding intermediate delivered by Hsp70-ADP ATP ATP ATP ATP ATP ATP ATP hydrolysis ATP hydrolysis ATP ATP ADP ADP ADP ADP ADP ADP ADP ADP ADP ADP ADP ADP ATP ATP ATP ATP ATP ATP ATP GroES