Table Of Content

Biochemistry, Molecular Biology, and Genetics Biochemistry, Molecular Biology, and Genetics Michael A. Lieberman, PhD Distinguished Teaching Professor Department of Molecular Genetics, Biochemistry, and Microbiology University of Cincinnati College of Medicine Cincinnati, Ohio Rick Ricer, MD Professor Emeritus Department of Family Medicine University of Cincinnati College of Medicine Cincinnati, Ohio Publisher: Michael Tully Acquisitions Editor: Susan Rhyner Product Manager: Stacey Sebring Marketing Manager: Joy Fisher-Williams Vendor Manager: Bridgett Dougherty Designer: Holly Reid McLaughlin Manufacturing Coordinator: Margie Orzech Compositor: S4 Carlisle 6th Edition Copyright © 2014, 2010, 2007, 1999, 1995 Lippincott Williams & Wilkins, a Wolters Kluwer business. 351 West Camden Street Two Commerce Square Baltimore, MD 21201 2001 Market Street Philadelphia, PA 19103 Printed in China All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written permission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. government employees are not covered by the above-mentioned copyright. To request permission, please contact Lippincott Williams & Wilkins at 2001 Market Street, Philadelphia, PA 19103, via email at [email protected], or via website at lww.com (products and services). Library of Congress Cataloging-in-Publication Data Lieberman, Michael, 1950- Biochemistry, molecular biology, and genetics. — 6th ed. / Michael A. Lieberman. p. ; cm. — (Board review series) Includes index. Rev. ed. of: Biochemistry, molecular biology, and genetics / Todd A. Swanson, Sandra I. Kim, Marc J. Glucksman. 5th ed. c2010. ISBN 978-1-4511-7536-3 I. Swanson, Todd A. Biochemistry, molecular biology, and genetics. II. Title. III. Series: Board review series. [DNLM: 1. Biochemical Phenomena—Examination Questions. 2. Biochemical Phenomena—Outlines. 3. Genetic Processes—Examination Questions. 4. Genetic Processes—Outlines. QU 18.2] QP518.3 572.8076—dc23 2013007054 DISCLAIMER Care has been taken to confirm the accuracy of the information present and to describe generally accepted practices. However, the authors, editors, and publisher are not responsible for errors or omissions or for any consequences from application of the information in this book and make no warranty, expressed or implied, with respect to the currency, completeness, or accuracy of the contents of the publication. Application of this information in a particular situation remains the professional responsibility of the practitioner; the clinical treatments described and recommended may not be considered absolute and universal recommendations. The authors, editors, and publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accordance with the current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any change in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new or infrequently employed drug. Some drugs and medical devices presented in this publication have Food and Drug Administration (FDA) clearance for limited use in restricted research settings. It is the responsibility of the health care provider to ascertain the FDA sta- tus of each drug or device planned for use in their clinical practice. To purchase additional copies of this book, call our customer service department at (800) 638-3030 or fax orders to (301) 223-2320. International customers should call (301) 223-2300. Visit Lippincott Williams & Wilkins on the Internet: http://www.lww.com. Lippincott Williams & Wilkins customer service representatives are available from 8:30 am to 6:00 pm, EST. 9 8 7 6 5 4 3 2 1 Preface and Acknowledgements This revision of BRS Biochemistry, Molecular Biology, and Genetics is intended to help students prepare for the United States Medical Licensing Examination (USMLE) Step 1, as well as other board examinations for students in health-related professions. The basic material of biochemistry is presented in an integrative fashion on the basis of the conviction that details are easier to remember if they are presented within the context of the physiologic functioning of the human body. It presents the essentials of biochemistry in the form of condensed descriptions and simple illustrations. Test questions at the end of the chapter emphasize important information and lead to a better understanding of the material. A comprehensive examination at the end of the book serves as a self-evaluation to help the student uncover areas of strength and weakness. We hope that this edition will aid students not only with the immediate task of passing a set of examinations, but also with the more long-term objective of fitting the subject of biochemistry into the framework of basic and clinical sciences, so essential to understanding their future patients’ problems. In a book of this nature it is possible that certain questions will have mixed interpreta- tions. Any errors in the book are the sole responsibility of the authors, and we would like to be informed of such errors, or alternative explanations. Through this feedback future print- ings of the book will reflect the correction of these errors. The authors would like to thank Dr. Anil Menon for his careful review of Chapter 10 (Human Genetics), and Stacey Sebring, our managing editor, for her patience with us as we worked on this revision of BRS Biochemistry, Molecular Biology, and Genetics. v How to Use this Book Anyone who has been teaching for a number of years knows that students, particularly those in medical school or in other programs within the health sciences, do not have an infinite amount of time to study or to review any given course. Therefore, this book was designed to make it easier for you to review biochemistry only at the depth you require, depending on the purpose for your review and the amount of time you have available. Each chapter begins with an overview in a shaded box. This overview serves as a sum- mation of the topics that will be covered in the chapter. In addition, these overviews help you review essential information quickly and reinforce key concepts. Clinical Correlates in each chapter provide additional clinical insight and relate basic biochemistry to actual medical practice. They are designed to challenge you and encourage assimilation of information. After you finish a chapter, try the questions and compare your answers to those in the explanations. As biochemistry is being integrated with other disciplines on NBME exams, a number of clinical questions require knowledge that would have been learned outside of a biochemistry class, and has not been reviewed in this text. If you have difficulty with the questions, review the chapter again and also look up relevant material from other courses in your curriculum for those questions which integrate biochemistry with another disci- pline. In addition to the questions in the print book, there are bonus questions available on the Point for further self-assessment and exam practice. By following the process outlined above, you can save time by reviewing only the topics you need to review and by concentrating only on the details you have forgotten. Michael A. Lieberman, PhD Rick Ricer, MD vi Contents Preface and Acknowledgements v How to Use this Book vi 1. FueL MetAboLisM AnD nutRition: bAsic PRinciPLes 1 i. Metabolic Fuels and Dietary Components 1 ii. The Fed or Absorptive State 5 iii. Fasting 7 iV. Prolonged Fasting (Starvation) 9 Review test 11 2. bAsic AsPects oF biocheMistRy: oRgAnic cheMistRy, AciD–bAse cheMistRy, AMino AciDs, PRotein stRuctuRe AnD Function, AnD enzyMe Kinetics 19 i. A Brief Review of Organic Chemistry 19 ii. Acids, Bases, and Buffers 20 iii. Amino Acids and Peptide Bonds 22 iV. Protein Structure 25 V. Enzymes 34 Review test 39 3. gene exPRession (tRAnscRiPtion), synthesis oF PRoteins (tRAnsLAtion), AnD ReguLAtion oF gene exPRession 51 i. Nucleic Acid Structure 52 ii. Synthesis of DNA (Replication) 58 iii. Synthesis of RNA (Transcription) 66 iV. Protein Synthesis (Translation of mRNA) 70 V. Regulation of Protein Synthesis 77 Vi. Recombinant DNA and Medicine 86 Review test 95 vii viii Contents 4. c eLL bioLogy, signAL tRAnsDuction, AnD the MoLecuLAR bioLogy oF cAnceR 109 i. Compartmentation in Cells; Cell Biology and Biochemistry 110 ii. Cell Signaling by Chemical Messengers 116 iii. The Molecular Biology of Cancer 125 iV. Cancer and Apoptosis 131 V. Cancer Requires Multiple Mutations 133 Vi. Viruses and Human Cancer 133 Review test 134 5. g eneRAtion oF AtP FRoM MetAboLic FueLs AnD oxygen toxicity 145 i. Bioenergetics 145 ii. Properties of Adenosine Triphosphate 147 iii. Electron Carriers and Vitamins 148 iV. TCA Cycle 154 V. Electron Transport Chain and Oxidative Phosphorylation 159 Vi. Oxygen Toxicity and Free-Radical Injury 164 Review test 170 6. cARbohyDRAte MetAboLisM 181 i. Carbohydrate Structure 181 ii. Proteoglycans, Glycoproteins, and Glycolipids 185 iii. Digestion of Carbohydrates 188 iV. Glycogen Structure and Metabolism 190 V. Glycolysis 197 Vi. Gluconeogenesis 204 Vii. Fructose and Galactose Metabolism 209 Viii. Pentose Phosphate Pathway 212 ix. Maintenance of Blood Glucose Levels 215 Review test 220 7. LiPiD AnD ethAnoL MetAboLisM 230 i. Lipid Structure 232 ii. Membranes 234 iii. Digestion of Dietary Triacylglycerol 235 iV. Fatty Acid and Triacylglycerol Synthesis 237 V. Formation of Triacylglycerol Stores in Adipose Tissue 242 Vi. Cholesterol and Bile Salt Metabolism 243 Vii. Blood Lipoproteins 246 Viii. Fate of Adipose Triacylglycerols 251 ix. Fatty Acid Oxidation 252 x. Ketone Body Synthesis and Utilization 257