ACTIVEMODELS LIBRARY OF PROTEINS AND NUCLEIC ACIDS ActiveModels sents an online library of macr olecular nuclic acids mentioned in the book and listed below.The hyperlinked text contrls the graphic display and presents a variety of perspectives and features End-of-chapter prob- lems written specifically to utilize this resource appear in most chapters Abl Kinase Cystic Fibrosis Transmer brane Conductance Regulator A nthetase e Domain) ne b Reductase AcrB Channel Actin Acyl-CoA Dehydrogenase Cytochrome c Oxidase (Rhodobacter sphaeroides Acvl-CoA Oxidase D2 Domain of NSf Adenylosuccinate lyase Dicer I B-Adrenergic Receptor Di-Heme Cytochrome c Alcohol Dehydrogenase 3,4-Dihydroxyphenylalanine Decarboxylase Aldose Reductase DNA Polymerase n a-Amylase (salivary DrrA Guanine Nucleotide Exchange Factor Amyloid beta-Peptide(AB) Dual Specificity Phosphatase 6 Androgen Recepto E1 Helicase Angiotension-1 Converting Enzyme(ACE) E1 Ubiquitin-like Protein Comple Anthrax Lethal Facto EGFR Kinase Domain Apoptosis-Inducing Factor rChannel) A2 reti Peptide Recepto te nd Bacterio i山Chain Bone etic Protein 2 Fetrochelatase (human) Moi Protein Domain Fibrin (human) BRCA2 FKBP12-Rapamycin Complex BtuB (Cobalamin transporter) Flavodoxin Calmodulin FliG (Flagellar Rotor Protein) Caspase-6 Fructose-1-6-Bisphosphatase Cat Allergen GABA Receptor Associated Protein Choline Acetyltranferase Galectin 1 (human) Chorismate Mutase Glucose-6-Phosphate Dehydrogenase Complex 1 (Electron Transport) Glutamine Synthetase Complex 2 (Electron Transport) Concanavalin ac ive Protein (human) Grb2 Growth Factor Bound Protein 2 Signal Transduction Adaptor GRD19p Cyclin-Dependent Kinase-2(human) Complex Cyclooxygenase Hemoglobin S
xxviii ActiveModels presents an online library of macromolecular structures with accompanying scripts detailing descriptions of structure-function relationships for the key proteins and nucleic acids mentioned in the book and listed below. The hyperlinked text controls the graphic display and presents a variety of perspectives and features. End-of-chapter problems written specifically to utilize this resource appear in most chapters. Abl Kinase Acetylcholinesterase (Recombinant Human) Acetyl-CoA Carboxylase (Carboxyltransferase Domain) AcrB Channel Actin Acyl-CoA Dehydrogenase Acyl-CoA Oxidase Adenylosuccinate Lyase b-Adrenergic Receptor Alcohol Dehydrogenase Aldose Reductase a-Amylase (salivary) Amyloid beta-Peptide (Ab) Androgen Receptor Angiotension-1 Converting Enzyme (ACE) Anthrax Lethal Factor Apoptosis-Inducing Factor Aprotinin Aqp1 Aquaporin (Water Channel) ASAP3 (ARF GTPase) ATP/ADP Translocase-1 Atrial Natriuretic Peptide Receptor Autotransporter (bacterial) BiP Chaperone Bone Morphogenetic Protein 2 Bone Morphogenetic Protein Domain BRCA 2 BtuB (Cobalamin transporter) Calmodulin Caspase-6 Cat Allergen Choline Acetyltranferase Chorismate Mutase Complex 1 (Electron Transport) Complex 2 (Electron Transport) Concanavalin C-Reactive Protein (human) Cu,Zn Superoxide Dismutase (human) Cyclin-Dependent Kinase-2 (human) Cyclooxygenase Cystic Fibrosis Transmembrane Conductance Regulator Cytidine Triphosphate Synthetase Cytochrome b Reductase Cytochrome c Cytochrome c Oxidase (Bos taurus) Cytochrome c Oxidase (Rhodobacter sphaeroides) D2 Domain of NSf Dicer I Di-Heme Cytochrome c 3,4-Dihydroxyphenylalanine Decarboxylase DNA Polymerase h DrrA Guanine Nucleotide Exchange Factor Dual Specificity Phosphatase 6 E1 Helicase E1 Ubiquitin-like Protein Complex EGFR Kinase Domain Elastase Enolase Enoyl-CoA Hydratase Estrogen Receptor Farnesyl Transferase Fatty Acid Transporter Ferritin (human) and Bacterioferritin Ferritin H Chain (human) Ferrochelatase (human) Fibrin (human) FKBP12-Rapamycin Complex Flavodoxin FliG (Flagellar Rotor Protein) Fructose-1-6-Bisphosphatase GABA Receptor Associated Protein Galectin 1 (human) Glucose-6-Phosphate Dehydrogenase Glutamine Synthetase Glycogen Phosphorylase GMP Synthetase Grb2 Growth Factor Bound Protein 2 Signal Transduction Adaptor GRD19p GroEL-GroES Complex Hemoglobin S ActiveModels Library of Proteins and Nucleic Acids Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
ActiveModels Library of Proteins and Nucleic Acids xxix Hepatocyte Nuclear Factor 1b Bound to DNA MDM2(Ubiquitin-Protein Ligase E3) Hexokinase(human) Metalloprotease HIV-1 Protease Methemoglobin (horse) HIV Reverse Transcriptase with a Rival Purine Inhibitor Monoamine Oxidase B(human) HIV Reverse Transcriptase with Inhibitor 7 Myoglobin HLA A2 Class I MH Myosin 2.heavy and light chain HMG CoA Reductase Myosin 2.heavy chain Hsp90 za Virus Hemagglutinin Nc6.& onoclonal Ab)Fab In Complex With Sweetene nte ept Ne se) ine/Threonine Kinase) coline Rece Dehyd Pick C:Chol TK-Sh2 Do nd to Pho tide ase red KIF1A(monomeric kin sin)-M N.Mi With Bound Myristovl-CoA NSE/NS4A Protease Apostructure(Hepatitis CVirus) Kinesin (rat) 23.-Oxidosa lene Cyclase with l anosterol Lactate Dehydrogenase(Malarial) p53-DNA Complex(p53 DNA-Binding Domain) LDL Receptor Pepsin DMSO Lipocalin (human) P-Glycoprotein (MDR) Luciferase Inhibitor Complex(firefly) Phosphofructokinase(Trypanosoma) Lysine Gingipain (Kgp)protein Phosphoglucoisomerase(Bacillus) Malonyl-CoA-ACP Transferase
ActiveModels Library of Proteins and Nucleic Acids xxix Hepatocyte Nuclear Factor 1b Bound to DNA Hexokinase (human) HIV-1 Protease HIV Reverse Transcriptase with a Rival Purine Inhibitor HIV Reverse Transcriptase with Inhibitor 7 HLA A2 Class I MHC HMG-CoA Reductase Hsp90 Influenza Virus Hemagglutinin Interleukin 17 Receptor Complex Interleukin -4 and its Receptor Ire1 (Transmembrane Serine/Threonine Kinase) Isocitrate Dehydrogenase ITK-Sh2 Domain Bound to Phosphopeptide KIF1A (monomeric kinesin)-Microtubule Complex) Kinesin Kinesin (rat) b-Lactamase Lactate Dehydrogenase (Malarial) LDL Receptor Lipocalin (human) Luciferase Inhibitor Complex (firefly) Lysine Gingipain (Kgp) protein Malonyl-CoA-ACP Transferase MDM2 (Ubiquitin-Protein Ligase E3) Metalloprotease Methemoglobin (horse) Monoamine Oxidase B (human) Myoglobin Myosin 2 - heavy and light chain Myosin 2 - heavy chain Myosin 5 Nc6.8 (monoclonal Ab) Fab In Complex With Sweetener Sc45647 Neuropsin (a Serine Protease) Nicotinic Acetylcholine Receptor Niemann-Pick C1: Cholesterol Nitrogenase Reductase N-Myristoyltransferase With Bound Myristoyl-CoA NSE/NS4A Protease Apostructure (Hepatitis C Virus) Nuclear Receptor X Heterodimers 2,3-Oxidosqualene Cyclase with Lanosterol p53-DNA Complex (p53 DNA-Binding Domain) Pepsin 1 DMSO P-Glycoprotein (MDR) Phosphofructokinase (Trypanosoma) Phosphoglucoisomerase (Bacillus) Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
LABORATORY TECHNIQUES IN BIOCHEMISTRY All of our knowledge of biochemistry is the outcome of exneriments for th this text presents biochemical knowle sight of the obligatory connection between scientific knowledge and its validation by obser vation and analysis The path of discovery by experimental research is often ind ct,tortu ous,ar con e trutn is oratory tech the heart o foster a dec understanding of the biochemical prir Recombinant DNA Techniques Fluxomics Section 17.5 Tumor diagnosis with positron emission tomography(PET) Sertion 18 7 riction mapping S 110.e Glucose monitoring devices Section 22 1 Nu otide seque cing Section 11. acid hybrid Section 11. Fluoro-substituted analogs as therapeutic agents Section26.8 nucleotides Section 11.6 "Knockout"mice Section 28.7 ant Dh Isolation/Purification of Macromolecules etic ol Section 122 Screening DNA libraries b dization Section 12.2b Protein nurifcation NA isolation Section 12.2e tion Section 52 onstruction of cDNA libraries Section 12.2e raphy Section5.2 sis Section 5.2 sed sen sDs.. e tags section 12.2e Southern blotting Section 12 2e Two-dimensional gel electronhoresis Section 5 2 Gene chips (DNA microarrays)Section 12.2f Protein expression from cDNA inserts Section 12.3 Hydrophobic interaction chromatography Section 5.2 Screening protein expression libraries with antibodies Section 12.3a High-performance liquid chromatography Section 5.2 Two-hybrid systems to identify protein:protein interactions Section 12.3c Affinity chromatography Section 5.2 Ultracentrifugation Section 5.2 Reporter gene constructs Section 12.3b Polymerase chain reaction(PCR)Section 11.1b Fractionation of cell extracts by centrifugation Section5.2 RT-qPCR(real-time quantitative PCR)Section 12.3a Proteomic analysis by MudPIT(Multidimensional Protein dentification Technology)Section 5.9b In vitro mutagenesis Section 12.3d ChlP-Seq(chromatin immunoprecipitation-DNA sequencing) Analyzing the Physical and Chemical Properties Section 12.3c of Biomolecules RNAi Section 12. Titration of weak acids Section 2.2 ser printing Section 12.5b ation of buffers Section 2.3 Edman degradation Section 4 3 Probing the Function of Biomolecules Nuclear magnetic resonance(NMR)Section 4.5 escent protein Section4.3 Estimation of protein concentration Section 5.2 ection 13.3 Amino acid analysis of proteins Section 4.6 Amino acid sequence determination Section 5.4 Mass spectrometry of proteins Section 5.4i Peptide mass fingerprinting Section 5.4i RNAi Section 12.4 Solid-phase peptide synthesis Section 5.6 NMR spe Membrane lipid phase transitions Section 9.4t imals sec tion 28 8 DNA nanotechnology Section 10.5 Section 28.1 Techniques Relevant to Clinical Biochemistry Single-mo e DNA sequencing Section 11. Gene therapy Section 12.6a Density gradient (isopycnic)centrifugation Section 11.3 analysis Section 175
xxx Recombinant DNA Techniques Restriction endonuclease digestion of DNA Section 10.6d Restriction mapping Section 10.6e–f Nucleotide sequencing Section 11.1 Nucleic acid hybridization Section 11.3 Chemical synthesis of oligonucleotides Section 11.6 Cloning; recombinant DNA constructions Section 12.1 Construction of genomic DNA libraries Section 12.2 Combinatorial libraries of synthetic oligomers Section 12.2 Screening DNA libraries by colony hybridization Section 12.2b mRNA isolation Section 12.2e Construction of cDNA libraries Section 12.2e Expressed sequence tags Section 12.2e Southern blotting Section 12.2e Gene chips (DNA microarrays) Section 12.2f Protein expression from cDNA inserts Section 12.3 Screening protein expression libraries with antibodies Section 12.3a Two-hybrid systems to identify protein:protein interactions Section 12.3c Reporter gene constructs Section 12.3b Polymerase chain reaction (PCR) Section 11.1b RT-qPCR (real-time quantitative PCR) Section 12.3a In vitro mutagenesis Section 12.3d ChIP-Seq (chromatin immunoprecipitation-DNA sequencing) Section 12.3c RNAi Section 12.4 DNA laser printing Section 12.5b BioBricks Section 12.7b CRISPR/Cas9 Section 12.7e Probing the Function of Biomolecules Green fluorescent protein Section 4.3 Plotting enzyme kinetic data Section 13.3j Enzyme inhibition Section 13.4 Optical trapping to measure molecular forces Section 16.2c Isotopic tracers as molecular probes Section 17.4b RNAi Section 12.4 NMR spectroscopy Section 17.4c Transgenic animals Section 28.8 DNA footprinting Section 28.1 Techniques Relevant to Clinical Biochemistry Gene therapy Section 12.6a Metabolomic analysis Section 17.5 Fluxomics Section 17.5 Tumor diagnosis with positron emission tomography (PET) Section 18.7 Glucose monitoring devices Section 22.1 Fluoro-substituted analogs as therapeutic agents Section 26.8 “Knockout” mice Section 28.7 Isolation/Purification of Macromolecules Ion exchange chromatography Section 5.2 Protein purification protocols Section 5.2 Dialysis and ultrafiltration Section 5.2 Size exclusion chromatography Section 5.2 SDS-polyacrylamide gel electrophoresis Section 5.2 Isoelectric focusing Section 5.2 Two-dimensional gel electrophoresis Section 5.2 Hydrophobic interaction chromatography Section 5.2 High-performance liquid chromatography Section 5.2 Affinity chromatography Section 5.2 Ultracentrifugation Section 5.2 Fractionation of cell extracts by centrifugation Section 5.2 Proteomic analysis by MudPIT (Multidimensional Protein Identification Technology) Section 5.9b Analyzing the Physical and Chemical Properties of Biomolecules Titration of weak acids Section 2.2a Preparation of buffers Section 2.3 Measurement of standard reduction potentials Section 3.9 Edman degradation Section 4.3 Nuclear magnetic resonance (NMR) Section 4.5 Estimation of protein concentration Section 5.2 Amino acid analysis of proteins Section 4.6 Amino acid sequence determination Section 5.4 Mass spectrometry of proteins Section 5.4i Peptide mass fingerprinting Section 5.4i Solid-phase peptide synthesis Section 5.6 Membrane lipid phase transitions Section 9.4b DNA nanotechnology Section 10.5a Nucleic acid hydrolysis Section 10.6 DNA sequencing Section 11.1 Single-molecule DNA sequencing Section 11.1 Density gradient (isopycnic) centrifugation Section 11.3 All of our knowledge of biochemistry is the outcome of experiments. For the most part, this text presents biochemical knowledge as established fact, but students should never lose sight of the obligatory connection between scientific knowledge and its validation by observation and analysis. The path of discovery by experimental research is often indirect, tortuous, and confounding before the truth is realized. Laboratory techniques lie at the heart of scientific inquiry, and many techniques of biochemistry are presented within these pages to foster a deeper understanding of the biochemical principles and concepts that they reveal. Laboratory Techniques in Biochemistry Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
PREFACE The Sixth Edition fenderstanding of the molr of g.Cures fo of cheaper and safer natural products are just a few practical benefits of this knowledge In addition.this expansion of information fuels,in the words of Thomas Jefferson theilimitab cientists can use the tools of b chemistry ore l aspects of a differentiation and develonment to analysis of its evolution and even its behavior Neu procedures based on the results of these explorations lie at the heart of the many modern che mistry is a science whose boun ries no en ompass all gy.an asp and to push the boundaries of their curiosity about science. Making Connections As the explication of natural phenomena rests more and more on biochemistry,its inclu sion in luate and th the ial featu in a scientists to make generalizations connecting the biochemical properties of living systems with the character of their constituent mole ules.As a cons ese general zati he functions and in predicting the mechanisms underlying newly discovered biomolecular processes Nevertheless,it is increasingly apparent that students must develop skills in inquiry-based learning,so that,beyond this nrst encounter with bio are equpped We are both biochemists but on of us is in a biology department,and the other is in a chemistry department.Undoubtedly,we each view biochemistry through the lens of menof our perspectives that will provide new dimensions of apprecia our respective Our Audience This biochemistry textbook is designed to communicate the fundamental principles governing the structure,function,and interactions of biological molecules to students encountering biochemistry for the first time.We aim to bring an appreciation of n eecu
xxxi The Sixth Edition Scientific understanding of the molecular nature of life is growing at an astounding rate. Significantly, society is the prime beneficiary of this increased understanding. Cures for diseases, better public health, remedies for environmental pollution, and the development of cheaper and safer natural products are just a few practical benefits of this knowledge. In addition, this expansion of information fuels, in the words of Thomas Jefferson, “the illimitable freedom of the human mind.” Scientists can use the tools of biochemistry and molecular biology to explore all aspects of an organism—from basic questions about its chemical composition, through inquiries into the complexities of its metabolism, its differentiation and development, to analysis of its evolution and even its behavior. New procedures based on the results of these explorations lie at the heart of the many modern medical miracles. Biochemistry is a science whose boundaries now encompass all aspects of biology, from molecules to cells, to organisms, to ecology, and to all aspects of health care. This sixth edition of Biochemistry embodies and reflects the expanse of this knowledge. We hope that this new edition will encourage students to ask questions of their own and to push the boundaries of their curiosity about science. Making Connections As the explication of natural phenomena rests more and more on biochemistry, its inclusion in undergraduate and graduate curricula in biology, chemistry, and the health sciences becomes imperative. The challenge to authors and instructors is a formidable one: how to familiarize students with the essential features of modern biochemistry in an introductory course or textbook. Fortunately, the increased scope of knowledge allows scientists to make generalizations connecting the biochemical properties of living systems with the character of their constituent molecules. As a consequence, these generalizations, validated by repetitive examples, emerge in time as principles of biochemistry, principles that are useful in discerning and describing new relationships between diverse biomolecular functions and in predicting the mechanisms underlying newly discovered biomolecular processes. Nevertheless, it is increasingly apparent that students must develop skills in inquiry-based learning, so that, beyond this first encounter with biochemical principles and concepts, students are equipped to explore science on their own. Much of the design of this new edition is meant to foster the development of such skills. We are both biochemists, but one of us is in a biology department, and the other is in a chemistry department. Undoubtedly, we each view biochemistry through the lens of our respective disciplines. We believe, however, that our collaboration on this textbook represents a melding of our perspectives that will provide new dimensions of appreciation and understanding for all students. Our Audience This biochemistry textbook is designed to communicate the fundamental principles governing the structure, function, and interactions of biological molecules to students encountering biochemistry for the first time. We aim to bring an appreciation of Preface Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it
xxxii Preface as m is an im understanding human physiology.To make this subject matter more relevant and inter esting to all readers,we emphasize.where appropriate.the biochemistry of humans. Objectives and Building on Previous Editions We carry forward the clarity of purpose found in previouseditions:namely.to illuminate 0 me time,th ew ed een revis to interrelationships of ideas so that students can begin to appreciate the overarching questions of biochemistry. Features Clarity of Instruction This edition was re-organized for increased clarity and read- ability.Many of the lengthier figure legends were shortened and more information was included directly within illustrations.These changes will help the more visual Visual Instruction The richness of the Protein Data Bank (www.pdb.org)and avail ular grap enlven t ate and inform the nd this book. Essential ouestio ter in this book is framed around an Essential Ouestion that invites students to beo ome actively engaged in their learnins and encou rages curiosity and imagination about the subject matter.For example,the Essential Q uestion of Cha ter 3 ask What are the lav s and principles of therm e n in hi n and as ors nizing princ iples for a lecture such as "What is the daily human requirement for ATP?"The subhe adings are designed to be concept statements that respond to the section headings.Th e end-of-chapter Summary then brings each question togethe 50 morant concepts and facts to At the end o each chap oter,a new Founda onal B cipal facts and conce nts that a student should understand after reading each cha Presented as short statements or descriptive phrases,the items of the Foundationa lists the students can review in assessing their learing End-of-Chapter Problems More than 600 end-of-chapter problems are provided.The elp stude nts develop pro olving skills tions to ind mathematical or fur Other questions address conceptual problems whose answers require application and integration of ideas and concepts introduced in the chapter.Each set of problems MCAI pra lents in their preparation for standard Further Readings sections at the end of each chapter make it easy for students to find up-to-date additional information about each topic
xxxii Preface biochemistry to a broad audience that includes undergraduates majoring in the life sciences, physical sciences, or premedical programs, as well as medical students and graduate students in the various health sciences for whom biochemistry is an important route to understanding human physiology. To make this subject matter more relevant and interesting to all readers, we emphasize, where appropriate, the biochemistry of humans. Objectives and Building on Previous Editions We carry forward the clarity of purpose found in previous editions; namely, to illuminate for students the principles governing the structure, function, and interactions of biological molecules. At the same time, this new edition has been revised to reflect tremendous developments in biochemistry. Significantly, emphasis is placed on the interrelationships of ideas so that students can begin to appreciate the overarching questions of biochemistry. Features ●● Clarity of Instruction This edition was re-organized for increased clarity and readability. Many of the lengthier figure legends were shortened and more information was included directly within illustrations. These changes will help the more visual reader. ●● Visual Instruction The richness of the Protein Data Bank (www.pdb.org) and availability of molecular graphics software has been exploited to enliven this text. Over 440 images of prominent proteins and nucleic acids involved with essential biological functions illustrate and inform the subject matter and were prepared especially for this book. ●● Essential Questions organization Each chapter in this book is framed around an Essential Question that invites students to become actively engaged in their learning and encourages curiosity and imagination about the subject matter. For example, the Essential Question of Chapter 3 asks, “What are the laws and principles of thermodynamics that allow us to describe the flows and interchanges of heat, energy, and matter in biochemical systems?” The section heads then pose Key Questions that serve as organizing principles for a lecture such as, “What is the daily human requirement for ATP?” The subheadings are designed to be concept statements that respond to the section headings. The end-of-chapter Summary then brings each question together with a synopsis of the answer that summarizes the important concepts and facts to aid students in organizing and understanding the material. ● Foundational Biochemistry At the end of each chapter, a new Foundational Biochemistry feature has been added. These sections provide a comprehensive list of the principal facts and concepts that a student should understand after reading each chapter. Presented as short statements or descriptive phrases, the items of the Foundational Biochemistry list serve as guides to students of the knowledge they have acquired from the chapter and as checklists the students can review in assessing their learning. ●● End-of-Chapter Problems More than 600 end-of-chapter problems are provided. They serve as meaningful exercises that help students develop problem-solving skills useful in achieving their learning goals. Some problems require students to employ calculations to find mathematical answers to relevant structural or functional questions. Other questions address conceptual problems whose answers require application and integration of ideas and concepts introduced in the chapter. Each set of problems includes MCAT practice questions to aid students in their preparation for standardized examinations such as the MCAT or GRE. ●● End-of-chapter problem headings allow students to place the problem within the context of the subject matter they have learned. ●● Further Readings sections at the end of each chapter make it easy for students to find up-to-date additional information about each topic. Copyright 2017 Cengage Learning. All Rights Reserved. May not be copied, scanned, or duplicated, in whole or in part. Due to electronic rights, some third party content may be suppressed from the eBook and/or eChapter(s). Editorial review has deemed that any suppressed content does not materially affect the overall learning experience. Cengage Learning reserves the right to remove additional content at any time if subsequent rights restrictions require it