(BQ) Part 1 book “Harper’s illustrated biochemistry” has contents: Structures & functions of proteins & enzymes; enzymes - kinetics, mechanism; regulation, & role of transition metals, bioenergetics, metabolism of carbohydrates, metabolism of lipids, metabolism of proteins & amino acids,… and other contents.
Copyright © 2018 by McGraw-Hill Education All rights reserved Except as permitted under the United States Copyright Act of 1976, no part of this publication may be reproduced or distributed in any form or by any means, or stored in a database or retrieval system, without the prior written permission of the publisher ISBN: 978-1-25-983794-4 MHID: 1-25-983794-7 The material in this eBook also appears in the print version of this title: ISBN: 978-1-25-983793-7, MHID: 1-25-983793-9 eBook conversion by codeMantra Version 1.0 All trademarks are trademarks of their respective owners Rather than put a trademark symbol after every occurrence of a trademarked name, we use names in an editorial fashion only, and to the benefit of the trademark owner, with no intention of infringement of the trademark Where such designations appear in this book, they have been printed with initial caps McGraw-Hill Education eBooks are available at special quantity discounts to use as premiums and sales promotions or for use in corporate training programs To contact a representative, please visit the Contact Us page at www.mhprofessional.com Notice Medicine is an ever-changing science As new research and clinical experience broaden our knowledge, changes in treatment and drug therapy are required The authors and the publisher of this work have checked with sources believed to be reliable in their efforts to provide information that is complete and generally in accord with the standards accepted at the time of publication However, in view of the possibility of human error or changes in medical sciences, neither the authors nor the publisher nor any other party who has been involved in the preparation or publication of this work warrants that the information contained herein is in every respect accurate or complete, and they disclaim all responsibility for any errors or omissions or for the results obtained from use of the information contained in this work Readers are encouraged to confirm the information contained herein with other sources For example and in particular, readers are advised to check the product information sheet included in the package of each drug they plan to administer to be certain that the information contained in this work is accurate and that changes have not been made in the recommended dose or in the contraindications for administration This recommendation is of particular importance in connection with new or infrequently used drugs TERMS OF USE This is a copyrighted work and McGraw-Hill Education and its licensors reserve all rights in and to the work Use of this work is subject to these terms Except as permitted under the Copyright Act of 1976 and the right to store and retrieve one copy of the work, you may not decompile, disassemble, reverse engineer, reproduce, modify, create derivative works based upon, transmit, distribute, disseminate, sell, publish or sublicense the work or any part of it without McGraw-Hill Education’s prior consent You may use the work for your own noncommercial and personal use; any other use of the work is strictly prohibited Your right to use the work may be terminated if you fail to comply with these terms THE WORK IS PROVIDED “AS IS.” McGRAW-HILL EDUCATION AND ITS LICENSORS MAKE NO GUARANTEES OR WARRANTIES AS TO THE ACCURACY, ADEQUACY OR COMPLETENESS OF OR RESULTS TO BE OBTAINED FROM USING THE WORK, INCLUDING ANY INFORMATION THAT CAN BE ACCESSED THROUGH THE WORK VIA HYPERLINK OR OTHERWISE, AND EXPRESSLY DISCLAIM ANY WARRANTY, EXPRESS OR IMPLIED, INCLUDING BUT NOT LIMITED TO IMPLIED WARRANTIES OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE McGraw-Hill Education and its licensors not warrant or guarantee that the functions contained in the work will meet your requirements or that its operation will be uninterrupted or error free Neither McGraw-Hill Education nor its licensors shall be liable to you or anyone else for any inaccuracy, error or omission, regardless of cause, in the work or for any damages resulting therefrom McGraw-Hill Education has no responsibility for the content of any information accessed through the work Under no circumstances shall McGraw-Hill Education and/or its licensors be liable for any indirect, incidental, special, punitive, consequential or similar damages that result from the use of or inability to use the work, even if any of them has been advised of the possibility of such damages This limitation of liability shall apply to any claim or cause whatsoever whether such claim or cause arises in contract, tort or otherwise Coauthors Peter L Gross, MD, MSc, FRCP(C) Associate Professor Department of Medicine McMaster University Hamilton, Ontario, Canada Molly Jacob MD, PhD Professor and Head Department of Biochemistry Christian Medical College Bagayam, Vellore, Tamil Nadu, India Peter A Mayes, PhD, DSc Professor (Emeritus) of Veterinary Biochemistry Royal Veterinary College University of London London, United Kingdom Robert K Murray, MD, PhD Professor (Emeritus) of Biochemistry University of Toronto Toronto, Ontario, Canada Margaret L Rand, PhD Senior Associate Scientist Division of Haematology/Oncology Hospital for Sick Children, Toronto, and Professor Department of Biochemistry University of Toronto, Toronto, Canada Joe Varghese, PhD Professor Department of Biochemistry Christian Medical College Bagayam, Vellore, Tamil Nadu, India Contents Preface SECTION I Structures & Functions of Proteins & Enzymes Biochemistry & Medicine Victor W Rodwell, PhD, & Robert K Murray, MD, PhD Water & pH Peter J Kennelly, PhD & Victor W Rodwell, PhD Amino Acids & Peptides Peter J Kennelly, PhD & Victor W Rodwell, PhD Proteins: Determination of Primary Structure Peter J Kennelly, PhD & Victor W Rodwell, PhD Proteins: Higher Orders of Structure Peter J Kennelly, PhD & Victor W Rodwell, PhD SECTION Enzymes: Kinetics, Mechanism, Regulation, & Role of Transition Metals II Proteins: Myoglobin & Hemoglobin Peter J Kennelly, PhD & Victor W Rodwell, PhD Enzymes: Mechanism of Action Peter J Kennelly, PhD & Victor W Rodwell, PhD Enzymes: Kinetics Victor W Rodwell, PhD Enzymes: Regulation of Activities Peter J Kennelly, PhD & Victor W Rodwell, PhD 10 The Biochemical Roles of Transition Metals Peter J Kennelly, PhD SECTION III Bioenergetics 11 Bioenergetics: The Role of ATP Kathleen M Botham, PhD, DSc & Peter A Mayes, PhD, DSc 12 Biologic Oxidation Kathleen M Botham, PhD, DSc & Peter A Mayes, PhD, DSc 13 The Respiratory Chain & Oxidative Phosphorylation Kathleen M Botham, PhD, DSc & Peter A Mayes, PhD, DSc SECTION 10 Which molecular feature listed causes duplex DNA to exhibit a nearconstant width along its long axis? A A purine nitrogenous base always pairs with another purine nitrogenous base B A pyrimidine nitrogenous base always pairs with another pyrimidine nitrogenous base C A pyrimidine nitrogenous base always pairs with a purine nitrogenous base D Repulsion between phosphate groups keeps the strands a uniform distance apart E Attraction between phosphate groups keeps the strands a uniform distance apart 10 The model for DNA replication first proposed by Watson and Crick posited that every newly replicated double-stranded daughter duplex DNA molecule A Was composed of the two strands from the parent DNA molecule B Contained solely the two newly synthesized strands of DNA C Contained two strands that are random mixtures of new and old DNA within each strand D Was composed of one strand derived from the original parental DNA duplex and one strand that was newly synthesized E Was composed of nucleotide sequences completely distinct from either parental DNA strand 11 Name the mechanism through which RNAs are synthesized from DNA A Replicational duplication B Translation C Translesion repair D Transesterification E Transcription 12 Which of the forces or interactions listed below play the predominant role in driving RNA secondary and tertiary structure formation? A Hydrophilic repulsion B Formation of complementary base pair regions 1105 C Hydrophobic interaction D van der Waals interactions E Salt bridge formation 13 Name the enzyme that synthesizes RNA from a double-stranded DNA template A RNA-dependent RNA polymerase B DNA-dependent RNA convertase C RNA-dependent replicase D DNA-dependent RNA polymerase E Reverse transcriptase 14 Define the most notable characteristic difference with regard to gene expression between eukaryotes and prokaryotes A Ribosomal RNA nucleotide lengths B Mitochondria C Lysosomes and peroxisomes D Sequestration of the genomic material in the nucleus E Chlorophyll 15 Which entry below correctly describes the approximate number of bp of DNA , which is separated into _chromosomes in atypical diploid human cell in a nonreplicating state? A 64 billion, 23 B 6.4 trillion, 46 C 23 billion, 64 D 64 billion, 46 E 6.4 billion, 46 16 What is the approximate number of base pairs associated with a single nucleosome? A 146 B 292 C 73 D 1460 E 900 1106 17 All but one of the following histones are found located within the superhelix formed between DNA and the histone octamer; which of the following is this histone? A Histone H2B B Histone H3 C Histone H1 D Histone H3 E Hisone H4 18 Chromatin can be broadly defined as active and repressed Which of the following is termed as a subclass of chromatin that is specifically inactivated at certain times within an organism’s life and/or in particular sets of differentiated cells? A Constitutive euchromatin B Facultative heterochromatin C Euchromatin D Constitutive heterochromatin 19 Which of the following hypothesizes that the physical and functional status of a certain region of genomic chromatin is dependent on the patterns of specific histone posttranslational modifications (PTMs), and/or DNA methylation status? A Morse code B PTM hypothesis C Nuclear body hypothesis D Epigenetic code E Genetic code 20 What is the name of the unusual repeated stretch of DNA localized at the tips of all eukaryotic chromosomes? A Kinetochore B Telomere C Centriole D Chromomere E Micromere 21 Given that DNA polymerases are unable to synthesize DNA without a 1107 primer, what molecule serves as the primer for these enzymes during DNA replication? A Five carbon sugars B Deoxyribose alone C A short RNA molecule D Proteins with free hydroxyl groups E Phosphomonoester 22 Which of the following terms is used for the discontinuous DNA replication that occurs during replication is catalyzed via the production of small DNA segments? A Okazaki fragments B Toshihiro pieces C Onishi oligonucleotides D Crick strands E Watson fragments 23 What molecule or force supplies the energy that drives the relief of mechanical strain by DNA gyrase? A Pyrimidine to purine conversion B Hydrolysis of GTP C Hydrolysis of ATP D Glycolysis E A proton gradient molecule or force 24 What is the name of the phase of the cell cycle between the conclusion of cell division and the beginning of DNA synthesis? A G1 B S C G2 D M E G0 25 At what stage of the cell cycle are key protein kinases, like cyclindependent kinase, activated? A Right before mitosis 1108 B At the beginning of S phase C Near the end of G1 phase D At the end of the G2 phase E All of the above 26 What disease is often associated with a breakdown of a cell’s ability to regulate/control its own division? A Kidney disease B Cancer C Emphysema D Diabetes E Heart disease 27 What is the molecular mechanism that is responsible for the quick decrease in the Cdk activity that leads to exit from the M phase and the entry into G1? A Drop in mitotic cyclin concentration B Decreased G1 cyclin concentration C Rise in G2 cyclin concentration D Rise in mitotic cyclin concentration E Rise in G1 cyclin concentration 28 Which of the following is the site to which RNA polymerase binds on the DNA template prior to the initiation of transcription? A Intron/exon junction B Open reading frame DNA C Terminator D Initiator methionine codon E Promoter 29 The large eukaryotic rRNA genes, such as 18S and 28S RNAencoding genes, are transcribed by which of the following RNA polymerases? A RNA polymerase III B RNA-dependent RNA polymerase δ C RNA polymerase I 1109 D RNA polymerase II E Mitochondrial RNA polymerase 30 Eukaryotic RNA polymerases all have a requirement for a large variety of accessory proteins to enable them to bind promoters and form physiologically relevant transcription complexes What are these proteins termed as? A Basal or general transcription factors B Activators C Accessory factors D Elongation factors E Facilitator polypeptides 31 The DNA segment from which the primary transcript is copied or transcribed is called which of the following? A Coding strand B Initiator methionine domain C Translation unit D Transcriptome E Initial codon 32 What class of DNA sequences are the eukaryotic genes that encode rRNAs? A Single-copy DNA B Highly repetitive DNA C Moderately repetitive DNA D Mixed sequence DNA 33 How the modifications to the nucleotides of the pre-tRNAs, prerRNAs, and pre-mRNAs occur? A Postprandially B Postmitotically C Pretranscriptionally D Posttranscriptionally E Prematurely 34 RNA polymerase II promoters are located on which side of the 1110 transcription unit? A Internal B 3′ downstream C Nearest to the C-terminus D Nearest to the N-terminus E 5′ upstream 35 With regard to eukaryotic mRNAs, which one of the following is not a normal property of mRNAs? A Eukaryotic mRNAs have special modifications at their 5′ (cap) and 3′ (poly(A) tail) termini B Are attached to ribosomes when they are translated C They are found in the cytoplasm within peroxisomes D Most have a significant noncoding segment that does not direct assembly of amino acids E Contain continuous nucleotide sequences that encode a particular polypeptide 36 Which of the following is the bond connecting the initiation nucleotide of the mRNA with the 5me-G Cap structure? A 3′-5′ phosphodiester bridge B 5′-5′ triphosphate bridge C 3′-3′ triphosphate bridge D 3′-5′ triphosphate bridge E 5′-3′ triphosphate bridge 37 What sequence feature of mature mRNAs listed below is thought to protect mRNAs from degradation? A Special posttranslational modifications B 3′ Poly(C)n tail C D E 5me-G Cap Introns Lariat structures 38 What could the consequences of inaccurate mRNA splicing be for the RNA? 1111 A B C D E A single base error at a splice junction will cause a large deletion A single base error at a splice junction will cause a large insertion A single base error at a splice junction will cause a large inversion C and E A single base error at a splice junction will change the reading frame and result in mRNA mistranslation 39 What is the macromolecular complex that associates with introns during mRNA splicing? A Splicer B Dicer C Nuclear body D Spliceosome E Slicer 40 What reaction does reverse transcriptase catalyze? A Translation of RNA to DNA B Transcription of DNA to RNA C Conversion of ribonucleotides into deoxyribonucleotides D Transcription of RNA to DNA E Conversion of a ribonucleotide to deoxynucleotides in the DNA double helix 41 RNAi or dsRNA-mediated RNA interference mediates which of the following? A RNA ligation B RNA silencing C RNA inversion D RNA restoration E RNA quelling 42 While the genetic code has 64 codons, there are only 20 naturally occurring amino acids Consequently, some amino acids are encoded by more than one codon This feature of the genetic code is an illustration of the genetic code being which of the following? A Degenerative B Duplicative 1112 C Nonoverlapping D Overlapping E Redundant 43 The genetic code contains how many termination codons? A B 21 C 61 D 64 E 20 44 If a tRNA has the sequence 5′-CAU-3′, what codon would it recognize (ignore wobble base pairing) A 3′-UAC-5′ B 3′-AUG-5′ C 5′-ATG-3′ D 5′-AUC-3′ E 5′-AUG-3′ 45 What is on the 3′ end of all functional, mature tRNAs? A The cloverleaf loop B The anticodon C The sequence CCA D The codon 46 Most aminoacyl-tRNA synthetases possess an activity that is shared with DNA polymerases This activity is a function A Proofreading B Hydrogenase C Proteolytic D Helicase E Endonucleolytic 47 Which of the following is the CORRECT order for the three distinct phases of protein synthesis? A Initiation, termination, elongation B Termination, initiation, elongation 1113 C Initiation, elongation, termination D Elongation, initiation, termination E Elongation, termination, initiation 48 Which amino acid is the initiating amino acid for essentially all proteins? A Cysteine B Threonine C Tryptophan D Methionine E Glutamic acid 49 The initiator tRNA is placed within the active 80S complex at which of the three-canonical ribosomal “sites” during protein synthesis? A E site B I site C P site D A site E Releasing factor binding site 50 Name the enzyme that forms the peptide bond during protein synthesis and define its chemical composition A Pepsynthase, protein B Peptidyl transferase, RNA C Peptidase, glycolipid D Peptidyl transferase, protein E GTPase, glycopeptide 51 What is the term used for mutations in the middle of an open reading frame that create a stop codon? A Frameshift mutation B Missense mutation C No-nonsense mutation D Point mutation E Nonsense mutation 52 What is the directionality of polypeptide synthesis? 1114 A B C D E C-terminal to N-terminal direction N-terminal to 3′ direction N-terminal to C-terminal direction 3′ to 5′ direction 5′ to 3′ direction 53 Which of the following cis-acting elements typically resides adjacent to or overlaps with many prokaryotic promoters? A Regulatory gene B Structural gene(s) C Repressor D Operator E Terminator 54 What is the term applied to a segment of a bacterial chromosome where genes for the enzymes of a particular metabolic pathway are clustered and subject to coordinate control? A Operon B Operator C Promoter D Terminal controller E Origin 55 What is the term applied to the complete collection of proteins present in a particular cell type? A Genome B Peptide collection C Transcriptome D Translatome E Proteome 56 How does nucleosome formation on genomic DNA affect the initiation and/or elongation phases of transcription? A Nucleosomes inhibit access of enzymes involved in all phases of transcription B Nucleosomes recruit histone and DNA-modifying enzymes, and the actions of these recruited enzymes affect the access of 1115 transcription proteins to DNA C Nucleosomes induce DNA degradation where the DNA contacts the histones D Nucleosomes have no significant effect on transcription 57 Which types of molecules interact with eukaryotic mRNA gene core promoter sites to facilitate the association of RNA polymerase II? A Termination factors B Sequence-specific transcription factors (transactivators) C Elongation factors D GTPases E General, or basal transcription factors (ie, the GTFs) 58 Most eukaryotic transcription factors contain at least two domains, each of which mediate different aspects of transcription factor function Which of the following are these domains? A RNA-binding domain and repression domain B Activation domain and repression domain C DNA-binding domain and activation domain D DNA-binding domain and ligand-binding domain E RNA-binding domain and the activation domain 59 Transcription factors bound at enhancers stimulate the initiation of transcription at the cis-linked core promoter through the action of intermediaries are termed as which of the following? A Coactivators B Cotranscription proteins C Corepressors D Receptors E Coordinators 60 What reactions among transcription proteins greatly expand the diversity of regulatory factors that can be generated from a small number of polypeptides? A Recombination B Homodimerization C Heterozygosity 1116 D Heterodimerization E Trimerization 61 The gene region containing the TATA box and extending to the transcription start site (TSS) is often termed which of the following? A Polymerase home B Initiator C Start selector D Core promoter E Operator 62 Which of the following possible mechanisms for how enhancers can stimulate transcription from great distances are currently thought to be CORRECT? A Enhancers can reversibly excise the intervening DNA between enhancers and promoters B RNA polymerase II binds avidly to enhancer sequences C Enhancers unwind DNA D Enhancers can search through DNA and bind directly to the associated core promoter E Enhancers and core promoters are brought into close proximity through DNA loop formation mediated by DNA-binding proteins 63 Which of the following histone amino acids are typically acetylated? A Lysine B Arginine C Asparagine D Histidine E Leucine 64 Place the following steps in order; what are the steps that occur sequentially during a transcription activation event following the binding of a transcriptional activator to its cognate activator–binding site on genomic DNA The chromatin remodeling complex binds to the core histones at the target region The combined actions of the various molecular complexes increase 1117 promoter accessibility to the transcriptional machinery The activator recruits a coactivator to a region of chromatin targeted for transcription Transcriptional machinery assembles at the site where transcription will be initiated The coactivator acetylates the core histones of nearby nucleosomes A B C D E 1–2–3–4–5 3–1–5–2–4 3–5–1–2–4 5–3–1–2–4 3–5–1–4–2 65 What strategy in transcription factor research allows for the simultaneous identification of all of the genomic sites bound by a given transcription factor under a given set of physiologic conditions? A Systematic deletion mapping B DNAse I sensitivity C Chromatin immunoprecipitation-sequencing (ChIP-seq) D FISH E Fluorescence lifetime imaging microscopy 66 Which sequences extend between the 5′–methylguanosine cap present on eukaryotic mRNAs to the AUG initiation codon? A Stop codon B Last exon C Last intron D 3′ UTR E 5′ UTR 67 Which of the following features of eukaryotic mRNA contribute importantly to message half-life? A 5′–UTR sequences B The promoter C The operator D 3′ UTR and poly(A) tail 1118 E The first intron *See glossary of terms at the end of this chapter 1119 ... publisher ISBN: 978 -1- 25-983794-4 MHID: 1- 25-983794-7 The material in this eBook also appears in the print version of this title: ISBN: 978 -1- 25-983793-7, MHID: 1- 25-983793-9 eBook conversion by... pleased to present the thirty-first edition of Harper’s Illustrated Biochemistry The first edition, entitled Harper’s Biochemistry, was published in 19 39 under the sole authorship of Dr Harold Harper... human subjects Changes in the Thirty-first Edition 17 As always, Harper’s Illustrated Biochemistry continues to emphasize the close relationship of biochemistry to the understanding of diseases,