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    148 visualizzazioni357 pagine

    Biochemestry

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    KAPLAN, .. c \ = (see \ medical 2 L/ O) oot ‘ee USMLE —~ $tep1 Lecture Notes TCA Author and Executive Editor Barbara Hansen, Ph.D. Chair of Biochemistry Deparment ‘Kaplan Medical igo AL Author Lynne B. Jorde, Ph.D. Profesor and Associate Charman Department of Human Genetics Univer of Utah Hlth Scenes Center Sal Lake Ci, UT Contributors Roger Lane, Ph.D. ‘Associate Profesor University of South Alabama Cole of Medicine Mobile AL ‘Vernon Reichenbacher, Ph.D. ‘Asocate Profesor Department of Biochemistry and Molecule Biology ‘Marshall Univesity Schoo of Medicine Huntington, WV Executive Director of Curriculum Richard Friedland, M.D. Director of Publishing and Media Michelle Covello ‘Medica Mustrator Christine Schaar ‘Managing Editor Kathlyn MeGreevy Production Editor Wiliam Ng Production Artist Michae! Wolf Cover Design Joanna Mylo Cover Art (Christine Schaar Rich LaRocco Contents Preface Section I: Molecular Biology and Biochemistry ‘Chapter 1: Nucleic Acid Structure and Organization ‘Chapter 2: DNA Replication and Repair we 6 Chapter 3: Transcription and RNA Processing Chapter 4: The Genetic Code, Mutation, and Translation coe Chapter 5: Genetic Regulation . . 7 Chapter 6: Recombinant DNA 8 Chapter 7: Genetic Testing ........- Chapter 8: Amino Acids, Proteins, and Enzymes... w Chapter 9: Hormones... rr Chapter 10: Vitamins us Chapter 11: Overview of Energy Metabolism... 155 Chapter 12: Glycoyss and Pyruvate Dehydrogenase... 6 (Chapter 15: irc Acid Cycle and Ondatve Phosphorylation ..........+. 179 Chapter 14: Giycogen, Gluconeogenesis, and the Hexose Monophosphate Sunt .......2-scecssesssesesseessees I (Chapter 15: Lipid Synthesis and Storage... ess. seeseeeseeeeee 207 thédical v indica Chapter 16: Lipid Mobilzaion and Catabolism... Chapter 17: Amino Add Metabolism ‘Chapter 18: Purine and Pyrimidine Metabolism Section II. Medical Genetics (Chapter 1: Single-Gene Disorders ‘Chapter 2: Population Genetics ...... Chapter 3: Cytogenetics ‘Chapter 4: Gene Mapping and Cloning Chapter 5: Genetics of Common Diseases (Chapter 6: Genetic Diagnosis and Gene Therapy ........ 25 24 265 35 335 345 Molecular Biology and Biochemistry Nucleic Acid Structure and Organization OVERVIEW: THE CENTRAL DOGMA OF MOLECULAR BIOLOGY ‘An organism must beable ta store and preserve its genetic information, pass that information long to future generations, and express that information asi carries out all the processes of Iie. The major steps involved in handing genetic information are illustrated by the central dogma of molecular biology (Figure I-1-1). Genetic information is stored inthe base sequence ‘of DNA molecules. imately, during th proces of gene expression this information is used to synthesize al the proteins made by an organism, Classically, a gene ia unit ofthe DNA that encodes a particalar protein or RNA molecule, Although this definition is now complicated by four increased appreciation ofthe ways in which genes may be expressed, ii til useful as general, working definition. Replication Transcription “Tansaton ‘NX ———+ va ——+ atte \N_/ Revise Transeption Figure A.The Central Dogme of Molecular Biology Gene Expression and DNA Replication (Gene expression and DNA replication are compared in Table I-1-1 Transcription, the frst stage in gene expression, involves trastr of information found in a double-stranded DNA molecule to the bse sequence ofa single-stranded RNA molecule, Ifthe RNA molecule isa messenger RNA. then the process known a translation converts the information in the RNA hase sequence to the amino acd sequence of a protein. ‘When cells divide, ech daughter cel must resive an eecurate copy ofthe genetic information. [DNA replication isthe process in which each chromosome is duplicated before cell division. 1. Comparison of Gene Expression and DNA. DNA Replication — | PsARentenion | Producealltheprotcns an organism | Dupliatesthe chvomovomes before cl _| | ies sion | “eanscrption of DNA: RNA copy DNA copy of entire chromosome cofsamallscion ofachromonome | (averages of human chromo- (avenge sz of buman gene, some, 1" nocetde pun) 10610 mci pas) | tandation of RA: protein yhese | Occurs throughout interphase ‘Occurs during $ phase 1 | Transition in aulus Replication in muceus | |) Translation in cytoplasm | “The concept ofthe cel eye (Figure T-1-2) canbe ued to describe the timing of some ofthese events in a cakaryotic eel The M phase (mitosis isthe time in which the cell vides to form two daughter cells. Interphase is the term used to describe the ime beoween two cel divisions ‘or mitoscs. Gene expression occurs throughout all stages of interphase. Interphase is subdivide eds follows + G, phase (gap 1) isa period of ellular growth preceding DNA synthesis. Call that Ihave stopped eclng, suchas muscle and nerve cells, are said tobe in a special state called Gy +S phase (DNA synthesis) isthe period of time during which DNA replication occurs, ‘Atthe end of S phase, each chromosome has doubled its DNA content and is com- posed of two identical sister chromatids inked atthe centromere. + G, phase (gap 2) is a period of cellular growth afer DNA synthesis but preceding Figure M12. mitosis Replicated DNA is checked for any errors before cll division, ‘Tho Eukaryot Col Cycle Reverse transcription, which produces DNA copies of an RNA, is more commonly associated with life cycles of retroviruses, which replicate and express their genome through a DNA inter- mediate (an integrated provirus). Reverse transcription also occurs to limited extent in human eel where it plays a role in amplifying certain highly epetive sequences in the DNA (Chapter 7) NUCLEOTIDE STRUCTURE AND NOMENCLATURE [Nuclei acids (DNA and RNA) are assembled from nucleotides, which consist of three compo: nents: nitrogenous bas, 2 fve-

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