STUDENT COMPANION to accompany Biochemistry, Fifth Edition Richard I. Gumport College of Medicine at Urbana-Champaign, University of Illinois Frank H. Deis Rutgers University Nancy Counts Gerber San Francisco State University Expanded Solutions to Text Problems contributed by Roger E. Koeppe, II University of Arkansas at Fayetteville W. H. Freeman and Company New York eISBN: 0-7167-9758-5 © 2002 by W. H. Freeman and Company No part of this book may be reproduced by any mechanical, photo- graphic, or electronic process, or in the form of a phonographic record- ing, nor may it be stored in a retrieval system, transmitted, or otherwise copied for public or private use, without written permission from the publisher. C O Preface, v N Acknowledgments, vii T E N PART I: THE MOLECULAR DESIGN OF LIFE T Chapter 1:Prelude 1 S Chapter 2:Biochemical Evolution 9 Chapter 3:Protein Structure and Function 17 Chapter 4:Exploring Proteins 33 Chapter 5:DNA, RNA, and the Flow of Genetic Information 51 Chapter 6:Exploring Genes 83 Chapter 7: Exploring Evolution 105 Chapter 8: Enzymes: Basic Concepts and Kinetics 115 Chapter 9: Catalytic Strategies 145 Chapter 10:Regulatory Strategies: Enzymes and Hemoglobin 159 Chapter 11:Carbohydrates 177 Chapter 12:Lipids and Cell Membranes 195 Chapter 13:Membrane Channels and Pumps 211 PART II: TRANSDUCING AND STORING ENERGY Chapter 14:Metabolism: Basic Concepts and Design 229 Chapter 15:Signal-Transduction Pathways: An Introduction to Information Metabolism 247 Chapter 16: Glycolysis and Gluconeogenesis 267 Chapter 17:The Citric Acid Cycle 287 Chapter 18:Oxidative Phosphorylation 305 Chapter 19:The Light Reactions of Photosynthesis 331 Chapter 20:The Calvin Cycle and the Pentose Phosphate Pathway 345 Chapter 21:Glycogen Metabolism 361 Chapter 22:Fatty Acid Metabolism 383 Chapter 23:Protein Turnover and Amino Acid Catabolism 407 PART III: SYNTHESIZING THE MOLECULES OF LIFE Chapter 24:The Biosynthesis of Amino Acids 425 Chapter 25:Nucleotide Biosynthesis 443 III IV CONTENTS Chapter 26:The Biosynthesis of Membrane Lipids and Steroids 461 Chapter 27:DNA Replication, Recombination, and Repair 481 Chapter 28:RNA Synthesis and Splicing 501 Chapter 29:Protein Synthesis 517 Chapter 30:The Integration of Metabolism 533 Chapter 31:The Control of Gene Expression 551 PART IV: RESPONDING TO ENVIRONMENTAL CHANGES Chapter 32:Sensory Systems 573 Chapter 33:The Immune System 585 Chapter 34:Molecular Motors 599 P R E F A C E Opening a comprehensive biochemistry text for the first time can be a daunt- ing experience for a neophyte. So much detailed material is presented that it is natural to wonder if you can possibly master it in one or two semesters of study. Of course, you can’t learn everything, but experience indicates that you can, indeed, learn the fundamental concepts in an introductory biochemistry course. We have written this Student Companion for Biochemistryto ease your entry into the exciting world of biochemistry. Your goal is to “know” and “understand” biochemistry. Unfortunately, awareness of these grand goals offers no practical help in reaching them, be- cause they are such high-level and complex intellectual processes. In addition, it is difficult for you to know to what extent you have attained them. We have found that, by subdividing these goals into simpler ones and expressing them in terms of demonstrable behaviors, you can begin to approach them and, in addition, can readily assay your progress toward reaching them. Thus, a part of each chapter consists of Learning Objectives that ask you to do things that will help you to begin to understand biochemistry. When you can master the objectives, you are well on your way to learning the material in the chapter. It is important to add a cautionary note here. Being able to respond to all the objectives adequately does not mean that you know biochemistry, for they are a limited sampling of all the possible objectives; more to the point, they do not explicitly require such higher-level activities as creation, analysis, integra- tion, synthesis, problem-solving, evaluation, application, and appreciation. These more advanced skills will develop to varying levels as you continue your studies of biochemistry beyond the introductory stage. Each chapter in the Companion consists of an introduction, Learning Objectives, a Self-Test, Answers to Self-Test, Problems, Answers to Problems, and Expanded Solutions to Text Problems. The introduction sets the scene, places the chapter material in the context of what you have already learned, and reminds you of material you may need to review in order to understand what follows. The Learning Objectives are presented in the order that the in- formation they encompass appears in Biochemistry. Key Words—important concepts or vocabulary—are italicized in the objectives. Self-Test questions, requiring primarily information recall, are followed by the answers to the questions. A Problems section, in which more complex skills are tested, is followed by answers to the problems. Finally, Expanded Solutions to end-of- chapter problems in the text are presented. The Companion may be used in many ways, and as you begin your studies you will develop the “system” that is best for you. Over 30 years of experience teaching introductory biochemistry to first-year medical students has suggested one pathway that you should consider. Start by reviewing the prerequisite chapters mentioned in the introduction and skim the Learning V VI PREFACE Objectives to obtain an overview of what you are to learn. Some students like also to skim the Self-Test questions at this time to form an impression of the levels of difficulty and the kinds of questions that will be asked. Next, read the chapter in Biochemistry, using the Learning Objectives to help direct you to the essential concepts. Note the Key Words and look up those you don’t know. Then attempt to meet the objectives. When you cannot satisfy an objective, reread the relevant section of the text. You should now take the Self-Test to check your ability to recall and apply what you have learned. Finally, solve the Problems, which have been designed to further test your ability to apply the knowledge you have gained. It is not sufficient simply to read the problems and look at the answers to see if you would have done them the same way. You must struggle through the solutions yourself to benefit from the problems. As you are using the Companion, you will, of course, be integrating what you have learned from your studies and your lectures or laboratory exercises. Besides helping you to learn biochemistry, you will find the Companion useful in study- ing for examinations. Go over each of the Learning Objectives in the chapters covered by an exam to ensure that you can respond to it knowledgeably. Similarly, review the Key Words. Decide which chapter topics you feel uncertain about and reread them. This protocol, cou- pled with a review of your lecture and reading notes, will prepare you well for examinations. It is important to talk about biochemistry with others in order to learn the pronuncia- tion of scientific terms and names and to help crystallize your thinking. Also, realize that al- though biochemistry has a sound foundation and we understand much about the chemistry of life, many of our concepts are hypotheses that will require modification or refinement as more experimental evidence accrues. Alternative and sometimes contradictory explanations exist for many biochemical observations. You should not regard the material in Biochemistry or the Companion as dogma, and you should, wherever possible, attempt to read about any given topic in at least two sources. Try to follow up topics that particularly interest you by reading about them in the scientific literature. References are given in Biochemistry, and your instructor can help you locate research and review articles. In this way, you can begin to ap- preciate the diversity of opinion and emphasis that exists in the field of biochemistry. The authors welcome readers’ comments, especially those drawing our attention to er- rors in the text. Comments should be sent to: Professor Richard I. Gumport Department of Biochemistry University of Illinois 600 S. Mathews Avenue Urbana, Illinois 61801-3792 e-mail [email protected] A C K N O W The Student Companion has its origins in a curriculum guide that was initi- L ated over 30 years ago for first-year medical students studying biochemistry E at the College of Medicine of the University of Illinois at Urbana-Champaign. D A number of colleagues have contributed to the Companion over the years. We especially wish to thank Ana Jonas, Richard Mintel, and Carl Rhodes, who G were authors on previous editions, for their contributions of concept and con- tent, which we continue to use. We also thank our colleagues Fumio M Matsumura, Gaetano Montelione, and Robert Niederman in the Department of Molecular Biology and Biochemistry at Rutgers University. We also thank E John Clark, Lowell Hager, Walter Mangel, William McClure, and Robert N Switzer for their efforts in helping to develop the initial curriculum guide. T Special thanks go to George Ordal and James Kaput, our fellow teachers of S biochemistry at the College of Medicine. We thank Gordon Lindberg and Chad Thomas for their careful reading and insightful contributions to the book. We also thank William Sorlie for educating us to the value of learning objectives. Thanks are also due to the many students who took the time to criticize the Companion. Finally, RIG appreciates the sustained support pro- vided our teaching efforts by the Department of Biochemistry and the College of Medicine at the University of Illinois. Richard I. Gumport Frank H. Deis Nancy C. Gerber VII The woods are lovely, dark, and deep, But I have promises to keep, And miles to go before I sleep, And miles to go before I sleep. ROBERT FROST C H Prelude: Biochemistry A P and the Genomic Revolution T E R 1 he introductory chapter of Biochemistrybegins by describing recent advances in T this exciting branch of science. We now know the complete genome sequences for several species, and have a nearly complete sequence for human DNA. The implications for biology and medicine are enormous, and they are touched on in this chapter. The authors begin with a brief explanation of the structures of DNA, RNA, and proteins. The unity of biochemistry is an important concept. It means that we can learn about human biochemistry by studying mice, yeast, bacteria, or any liv- ing organism. Many biochemical interactions depend on weak noncovalent interac- tions. Because the great majority of biochemical processes occur in water, the properties of water and their effects on biomolecules are also described. Then fol- lows a discussion of entropy, energy, and the laws of thermodynamics. This provides a basis for understanding hydrophobic interactions and protein folding. Then the authors highlight the impact of biochemistry on modern biology and medicine. Finally, an appendix presents the most popular molecular models and other repre- sentations used by biochemists. 11