USMLE ® USMLE Step Biochem.indb STEP Lecture Notes 2018 Biochemistry and Medical Genetics 9/15/17 11:01 AM USMLE® is a joint program of the Federation of State Medical Boards (FSMB) and the National Board of Medical Examiners (NBME), neither of which sponsors or endorses this product. This publication is designed to provide accurate information in regard to the subject matter covered as of its publication date, with the understanding that knowledge and best practice constantly evolve The publisher is not engaged in rendering medical, legal, accounting, or other professional service If medical or legal advice or other expert assistance is required, the services of a competent professional should be sought This publication is not intended for use in clinical practice or the delivery of medical care To the fullest extent of the law, neither the Publisher nor the Editors assume any liability for any injury and/or damage to persons or property arising out of or related to any use of the material contained in this book © 2018 by Kaplan, Inc. Published by Kaplan Medical, a division of Kaplan, Inc 750 Third Avenue New York, NY 10017 10 Course ISBN-13: 978-1-5062-2827-3 All rights reserved The text of this publication, or any part thereof, may not be reproduced in any manner whatsoever without written permission from the publisher This item comes as a set and should not be broken out and sold separately Retail ISBN-13: 978-1-5062-3954-5 Kaplan Publishing print books are available at special quantity discounts to use for sales promotions, employee premiums, or educational purposes For more information or to purchase books, please call the Simon & Schuster special sales department at 866-506-1949 USMLE Step Biochem.indb 9/15/17 11:01 AM Editor Sam Turco, PhD Professor, Department of Biochemistry University of Kentucky College of Medicine Lexington, KY Contributors Roger Lane, PhD Professor, Department of Biochemistry University of South Alabama College of Medicine Mobile, AL Ryan M Harden, MD, MS Physician, Family Medicine Gateway Family Health Clinic, Ltd Sandstone, MN Assistant Professor, Department of Family Medicine and Community Health University of Minnesota Medical School, Duluth Campus Duluth, MN USMLE Step Biochem.indb 9/15/17 11:01 AM We want to hear what you think What you like or not like about the Notes? Please email us at medfeedback@kaplan.com USMLE Step Biochem.indb 9/15/17 11:01 AM Table of Contents Part I: Biochemistry Chapter 1: Nucleic Acid Structure and Organization�����������������������������������3 Chapter 2: DNA Replication and Repair ����������������������������������������������������� 17 Chapter 3: Transcription and RNA Processing �������������������������������������������33 Chapter 4: The Genetic Code, Mutations, and Translation �����������������������49 Chapter 5: Regulation of Eukaryotic Gene Expression�������������������������������75 Chapter 6: Genetic Strategies in Therapeutics �������������������������������������������87 Chapter 7: Techniques of Genetic Analysis�����������������������������������������������103 Chapter 8: Amino Acids, Proteins, and Enzymes������������������������������������� 119 Chapter 9: Hormones���������������������������������������������������������������������������������135 Chapter 10: Vitamins�����������������������������������������������������������������������������������149 Chapter 11: Energy Metabolism�����������������������������������������������������������������163 Chapter 12: Glycolysis and Pyruvate Dehydrogenase����������������������������� 175 Chapter 13: Citric Acid Cycle and Oxidative Phosphorylation�����������������193 Chapter 14: Glycogen, Gluconeogenesis, and the Hexose Monophosphate Shunt�����������������������������������������������������������205 Chapter 15: Lipid Synthesis and Storage���������������������������������������������������223 Chapter 16: Lipid Mobilization and Catabolism���������������������������������������243 Chapter 17: Amino Acid Metabolism���������������������������������������������������������265 Chapter 18: Purine and Pyrimidine Metabolism���������������������������������������289 v 00_USMLE_FM.indd 9/25/17 4:59 PM Part II: Medical Genetics Chapter 1: Single-Gene Disorders��������������������������������������������������������������� 303 Chapter 2: Population Genetics������������������������������������������������������������������� 333 Chapter 3: Cytogenetics������������������������������������������������������������������������������� 347 Chapter 4: Genetics of Common Diseases��������������������������������������������������371 Chapter 5: Recombination Frequency��������������������������������������������������������� 379 Chapter 6: Genetic Diagnosis����������������������������������������������������������������������� 391 Index 407 Additional resources available at www.kaptest.com/usmlebookresources vi USMLE Step Biochem.indb 9/15/17 11:01 AM PART I Biochemistry USMLE Step Biochem.indb 9/15/17 11:01 AM USMLE Step Biochem.indb 9/15/17 11:01 AM Nucleic Acid Structure and Organization Learning Objectives ❏❏ Explain information related to nucleotide structure and nomenclature ❏❏ Use knowledge of organization of DNA versus RNA ❏❏ Understand general features of a chromosome CENTRAL DOGMA OF MOLECULAR BIOLOGY An organism must be able to store and preserve its genetic information, pass that information along to future generations, and express that information as it carries out all the processes of life The major steps involved in handling genetic information are illustrated by the central dogma of molecular biology. Replication Translation Transcription RNA DNA Protein Reverse transcription FigureI-1-1 I-1-1.Central Central Dogma of Molecular Biology Figure Dogma of Molecular Biology Genetic information is stored in the base sequence of DNA molecules Ultimately, during the process of gene expression, this information is used to synthesize all the proteins made by an organism. HY Classically, a gene is a unit of the DNA that encodes a particular protein MY or RNA molecule Although this definition is now complicated by our increased appreciation LY of the ways in which genes may be expressed, it is still useful as a working definition Gene Expression and DNA Replication High-Yield Gene expression and DNA replication are compared below.MEDIUM Transcription, YIELD the first stage in gene expression, involves transfer of information found in a douLOW YIELD ble-stranded DNA molecule to the base sequence of a single-stranded RNA molecule If the RNA molecule is a messenger RNA, then the process known as translation converts the information in the RNA base sequence to the amino FUNDAMENTALS acid sequence of a protein REINFORCEMENT HY MY LY HIGH YIELD MEDIUM YIELD LOW YIELD FUNDAMENTALS REINFORCEMENT USMLE Step Biochem.indb 9/15/17 11:01 AM ... Renaturation of DNA Double-stranded DNA Denaturation (heat) Medical Genetics Behavioral Science/ Social Sciences Single-stranded DNA Renaturation (cooling) Double-stranded DNA Figure I-1-9 Denaturation... Biochem.indb 9/15/17 11:01 AM Immunology Part I Biochemistry ● Biochemistry 5´- Phosphate 3´- Hydroxyl O O Medical Genetics P O O 5´CH2 5´ Behavioral Science/ Social Sciences H H 3C O T O N N N N H A N H... 11 9/15/17 11:01 AM Immunology Part I ● Biochemistry Biochemistry Less active More active Medical Genetics DNA double helix Behavioral Science/ Social Sciences 10 nm chromatin (nucleosomes) 30