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Essential Biochemistry, 5th Edition is comprised of biology, pre-med and allied health topics and presents a broad, but not overwhelming, base of biochemical coverage that focuses on the chemistry behind the biology. This revised edition relates the chemical concepts that scaffold the biology of biochemistry, providing practical knowledge as well as many problem-solving opportunities to hone skills. Key Concepts and Concept Review features help students to identify and review important takeaways in each section.
Contents
Preface xiv
Part 1 Foundations
1 The Chemical Basis of Life 1
1.1 What Is Biochemistry? 1
1.2 Biological Molecules 3
Cells contain four major types of biomolecules 3
There are three major kinds of biological polymers 6
Box 1.A Units Used in Biochemistry 7
1.3 Energy and Metabolism 10
Enthalpy and entropy are components of free energy 11
ΔG is less than zero for a spontaneous process 12
Life is thermodynamically possible 12
1.4 The Origin of Cells 14
Prebiotic evolution led to cells 15
Box 1.B How Does Evolution Work? 17
Eukaryotes are more complex than prokaryotes 17
The human body includes microorganisms 19
2 Aqueous Chemistry 27
2.1 Water Molecules and Hydrogen Bonds 27
Hydrogen bonds are one type of electrostatic force 29
Water dissolves many compounds 31
Box 2.A Why Do Some Drugs Contain Fluorine? 31
2.2 The Hydrophobic Effect 33
Amphiphilic molecules experience both hydrophilic interactions and the hydrophobic effect 35
The hydrophobic core of a lipid bilayer is a barrier to diffusion 35
Box 2.B Sweat, Exercise, and Sports Drinks 36
2.3 Acid-Base Chemistry 37
[H+] and [OH-] are inversely related 38
The pH of a solution can be altered 39
Box 2.C Atmospheric CO2 and Ocean Acidification 39
A pK value describes an acid's tendency to ionize 40
The pH of a solution of acid is related to the pK 41
2.4 Tools and Techniques: Buffers 44
2.5 Clinical Connection: Acid-Base Balance in Humans 46
Part 2 Molecular Structure and Function
3 Nucleic Acid Structure and Function 57
3.1 Nucleotides 57
Nucleic acids are polymers of nucleotides 58
Some nucleotides have other functions 60
3.2 Nucleic Acid Structure 61
DNA is a double helix 62
RNA is single-stranded 64
Nucleic acids can be denatured and renatured 64
3.3 The Central Dogma 67
Box 3.A Replication, Mitosis, Meiosis, and Mendel's Laws 67
DNA must be decoded 70
A mutated gene can cause disease 71
Genes can be altered 72
Box 3.B Genetically Modified Organisms 73
3.4 Genomics 74
The exact number of human genes is not known 75
Genome size varies 75
Genomics has practical applications 77
Box 3.C Viruses 78
4 Protein Structure 86
4.1 Amino Acids, the Building Blocks of Proteins 86
The 20 amino acids have different chemical properties 88
Box 4.A Does Chirality Matter? 89
Box 4.B Monosodium Glutamate 91
Peptide bonds link amino acids in proteins 91
The amino acid sequence is the first level of protein structure 94
4.2 Secondary Structure: The Conformation of the Peptide Group 95
The α helix exhibits a twisted backbone conformation 96
The β sheet contains multiple polypeptide strands 96
Proteins also contain irregular secondary structure 98
4.3 Tertiary Structure and Protein Stability 99
Proteins can be described in different ways 99
Globular proteins have a hydrophobic core 100
Protein structures are stabilized mainly by the hydrophobic effect 101
Box 4.C Thioester Bonds as Spring-Loaded Traps 103
Protein folding is a dynamic process 103
Box 4.D Baking and Gluten Denaturation 104
Disorder is a feature of many proteins 105
Protein functions may depend on disordered regions 106
4.4 Quaternary Structure 107
4.5 Clinical Connection: Protein Misfolding and Disease 109
4.6 Tools and Techniques: Analyzing Protein Structure 111
Chromatography takes advantage of a polypeptide's unique properties 111
Mass spectrometry reveals amino acid sequences 114
Box 4.E Mass Spectrometry Applications 116
Protein structures are determined by NMR spectroscopy, X-ray crystallography, and cryo-electron microscopy 116
5 Protein Function 125
5.1 Myoglobin and Hemoglobin: Oxygen-Binding Proteins 126
Oxygen binding to myoglobin depends on the oxygen concentration 127
Myoglobin and hemoglobin are related by evolution 128
Oxygen binds cooperatively to hemoglobin 129
A conformational shift explains hemoglobin's cooperative behavior 130
Box 5.A Carbon Monoxide Poisoning 130
H+ ions and bisphosphoglycerate regulate oxygen binding to hemoglobin in vivo 132
5.2 Clinical Connection: Hemoglobin Variants 134
5.3 Structural Proteins 136
Actin filaments are most abundant 137
Actin filaments continuously extend and retract 138
Tubulin forms hollow microtubules 139
Keratin is an intermediate filament 142
Collagen is a triple helix 144
Box 5.B Vitamin C Deficiency Causes Scurvy 144
Collagen molecules are covalently cross-linked 145
Box 5.C Bone and Collagen Defects 147
5.4 Motor Proteins 148
Myosin has two heads and a long tail 148
Myosin operates through a lever mechanism 150
Kinesin is a microtubule-associated motor protein 151
Box 5.D Myosin Mutations and Deafness 151
Kinesin is a processive motor 152
5.5 Antibodies 154
Immunoglobulin G includes two antigen-binding sites 154
B lymphocytes produce diverse antibodies 156
Researchers take advantage of antibodies' affinity and specificity 157
6 How Enzymes Work 167
6.1 What Is an Enzyme? 167
Enzymes are usually named after the reaction they catalyze 170
6.2 Chemical Catalytic Mechanisms 171
A catalyst provides a reaction pathway with a lower activation energy barrier 173
Enzymes use chemical catalytic mechanisms 173
Box 6.A Depicting Reaction Mechanisms 175
The catalytic triad of chymotrypsin promotes peptide bond hydrolysis 177
6.3 Unique Properties of Enzyme Catalysts 180
Enzymes stabilize the transition state 180
Efficient catalysis depends on proximity and orientation effects 181
The active-site microenvironment promotes catalysis 182
6.4 Chymotrypsin in Context 183
Not all serine proteases are related by evolution 183
Enzymes with similar mechanisms exhibit different substrate specificity 184
Chymotrypsin is activated by proteolysis 185
Protease inhibitors limit protease activity 186
6.5 Clinical Connection: Blood Coagulation 187
7 Enzyme Kinetics and Inhibition 198
7.1 Introduction to Enzyme Kinetics 198
7.2 Derivation and Meaning of the Michaelis-Menten Equation 201
Rate equations describe chemical processes 201
The Michaelis-Menten equation is a rate equation for an enzyme-catalyzed reaction 202
KM is the substrate concentration at which velocity is half-maximal 204
The catalytic constant describes how quickly an enzyme can act 204
kcat/KM indicates catalytic efficiency 205
KM and Vmax are experimentally determined 205
Not all enzymes fit the simple Michaelis-Menten model 207
7.3 Enzyme Inhibition 209
Some inhibitors act irreversibly 209
Competitive inhibition is the most common form of reversible enzyme inhibition 210
Transition state analogs inhibit enzymes 212
Other types of inhibitors affect Vmax 213
Box 7.A Inhibitors of HIV Protease 214
Allosteric enzyme regulation includes inhibition and activation 216
Several factors may influence enzyme activity 219
7.4 Clinical Connection: Drug Development 219
8 Lipids and Membranes 234
8.1 Lipids 234
Fatty acids contain long hydrocarbon chains 235
Box 8.A Omega-3 Fatty Acids 236
Some lipids contain polar head groups 237
Lipids perform a variety of physiological functions 239
Box 8.B The Lipid Vitamins A, D, E, and K 240
8.2 The Lipid Bilayer 241
The bilayer is a fluid structure 242
Natural bilayers are asymmetric 243
8.3 Membrane Proteins 244
Integral membrane proteins span the bilayer 245
An α helix can cross the bilayer 245
A transmembrane β sheet forms a barrel 246
Lipid-linked proteins are anchored in the membrane 246
8.4 The Fluid Mosaic Model 248
Membrane proteins have a fixed orientation 249
Lipid asymmetry is maintained by enzymes 250
9 Membrane Transport 258
9.1 The Thermodynamics of Membrane Transport 258
Ion movements alter membrane potential 259
Membrane proteins mediate transmembrane ion movement 260
9.2 Passive Transport 263
Porins are β barrel proteins 263
Ion channels are highly selective 264
Gated channels undergo conformational changes 265
Box 9.A Pores Can Kill 265
Aquaporins are water-specific pores 266
Some transport proteins alternate between conformations 268
9.3 Active Transport 269
The Na,K-ATPase changes conformation as it pumps ions across the membrane 269
ABC transporters mediate drug resistance 271
Secondary active transport exploits existing gradients 271
9.4 Membrane Fusion 272
SNAREs link vesicle and plasma membranes 273
Box 9.B Antidepressants Block Serotonin Transport 275
Endocytosis is the reverse of exocytosis 276
Autophagosomes enclose cell materials for degradation 277
Box 9.C Exosomes 278
10 Signaling 287
10.1 General Features of Signaling Pathways 287
A ligand binds to a receptor with a characteristic affinity 288
Most signaling occurs through two types of receptors 289
The effects of signaling are limited 290
10.2 G Protein Signaling Pathways 291
G protein-coupled receptors include seven transmembrane helices 292
The receptor activates a G protein 293
The second messenger cyclic AMP activates protein kinase A 294
Arrestin competes with G proteins 296
Signaling pathways must be switched off 296
The phosphoinositide signaling pathway generates two second messengers 297
Many sensory receptors are GPCRs 298
Box 10.A Opioids 299
10.3 Receptor Tyrosine Kinases 300
The insulin receptor dimer changes conformation 300
The receptor undergoes autophosphorylation 302
Box 10.B Cell Signaling and Cancer 303
10.4 Lipid Hormone Signaling 303
Eicosanoids are short-range signals 305
Box 10.C Inhibitors of Cyclooxygenase 306
11 Carbohydrates 315
11.1 Monosaccharides 315
Most carbohydrates are chiral compounds 316
Cyclization generates α and β anomers 317
Monosaccharides can be derivatized in many different ways 318
Box 11.A The Maillard Reaction 319
11.2 Polysaccharides 320
Lactose and sucrose are the most common disaccharides 321
Starch and glycogen are fuel-storage molecules 321
Cellulose and chitin provide structural support 322
Box 11.B Cellulosic Biofuel 323
Bacterial polysaccharides form a biofilm 324
11.3 Glycoproteins 325
Oligosaccharides are N-linked or O-linked 325
Oligosaccharide groups are biological markers 326
Box 11.C The ABO Blood Group System 327
Proteoglycans contain long glycosaminoglycan chains 327
Bacterial cell walls are made of peptidoglycan 328
Part 3 Metabolism
12 Metabolism and Bioenergetics 337
12.1 Food and Fuel 337
Cells take up the products of digestion 338
Monomers are stored as polymers 339
Fuels are mobilized as needed 340
12.2 Metabolic Pathways 343
Some major metabolic pathways share a few common intermediates 343
Many metabolic pathways include oxidation-reduction reactions 344
Metabolic pathways are complex 346
Human metabolism depends on vitamins 347
Box 12.A The Transcriptome, the Proteome, and the Metabolome 348
Box 12.B Iron Metabolism 351
12.3 Free Energy Changes in Metabolic Reactions 352
The free energy change depends on reactant concentrations 352
Unfavorable reactions are coupled to favourable reactions 354
Energy can take different forms 356
Regulation occurs at the steps with the largest free energy changes 357
13 Glucose Metabolism 366
13.1 Glycolysis 366
Energy is invested at the start of glycolysis 367
ATP is generated near the end of glycolysis 373
Box 13.A Catabolism of Other Sugars 378
Some cells convert pyruvate to lactate or ethanol 379
Box 13.B Alcohol Metabolism 380
Pyruvate is the precursor of other molecules 381
13.2 Gluconeogenesis 383
Four gluconeogenic enzymes plus some glycolytic enzymes convert pyruvate to glucose 383
Gluconeogenesis is regulated at the fructose bisphosphatase step 385
13.3 Glycogen Synthesis and Degradation 386
Glycogen synthesis consumes the energy of UTP 386
Glycogen phosphorylase catalyzes glycogenolysis 388
13.4 The Pentose Phosphate Pathway 389
The oxidative reactions of the pentose phosphate pathway produce NADPH 389
Isomerization and interconversion reactions generate a variety of monosaccharides 390
A summary of glucose metabolism 392
13.5 Clinical Connection: Disorders of Carbohydrate Metabolism 393
Glycogen storage diseases affect liver and muscle 394
14 The Citric Acid Cycle 403
14.1 The Pyruvate Dehydrogenase Reaction 403
The pyruvate dehydrogenase complex contains multiple copies of three different enzymes 404
Pyruvate dehydrogenase converts pyruvate to acetyl-CoA 404
14.2 The Eight Reactions of the Citric Acid Cycle 406
1. Citrate synthase adds an acetyl group to oxaloacetate 407
2. Aconitase isomerizes citrate to isocitrate 409
3. Isocitrate dehydrogenase releases the first CO2 410
4. α-Ketoglutarate dehydrogenase releases the second CO2 410
5. Succinyl-CoA synthetase catalyzes substrate-level phosphorylation 411
6. Succinate dehydrogenase generates ubiquinol 412
7. Fumarase catalyzes a hydration reaction 412
8. Malate dehydrogenase regenerates oxaloacetate 412
14.3 Thermodynamics of the Citric Acid Cycle 413
The citric acid cycle is an energy-generating catalytic cycle 413
The citric acid cycle is regulated at three steps 414
Box 14.A Mutations in Citric Acid Cycle Enzymes 415
The citric acid cycle probably evolved as a synthetic pathway 415
14.4 Anabolic and Catabolic Functions of the Citric Acid Cycle 416
Citric acid cycle intermediates are precursors of other molecules 416
Anaplerotic reactions replenish citric acid cycle intermediates 418
Box 14.B The Glyoxylate Pathway 419
15 Oxidative Phosphorylation 428
15.1 The Thermodynamics of Oxidation-Reduction Reactions 428
Reduction potential indicates a substance's tendency to accept electrons 429
The free energy change can be calculated from the change in reduction potential 431
15.2 Mitochondrial Electron Transport 432
Mitochondrial membranes define two compartments 433
Complex I transfers electrons from NADH to ubiquinone 434
Other oxidation reactions contribute to the ubiquinol pool 436
Complex III transfers electrons from ubiquinol to cytochrome c 437
Complex IV oxidizes cytochrome c and reduces O2 439
Respiratory complexes associate with each other 441
Box 15.A Reactive Oxygen Species 442
15.3 Chemiosmosis 443
Chemiosmosis links electron transport and oxidative phosphorylation 443
The proton gradient is an electrochemical gradient 443
15.4 ATP Synthase 445
Proton translocation rotates the c ring of ATP synthase 445
The binding change mechanism explains how ATP is made 447
The P:O ratio describes the stoichiometry of oxidative phosphorylation 447
Box 15.B Uncoupling Agents Prevent ATP Synthesis 448
The rate of oxidative phosphorylation reflects the need for ATP 448
Box 15.C Powering Human Muscles 449
16 Photosynthesis 458
16.1 Chloroplasts and Solar Energy 458
Pigments absorb light of different wavelengths 459
Light-harvesting complexes transfer energy to the reaction center 461
16.2 The Light Reactions 463
Photosystem II is a light-activated oxidation-reduction enzyme 463
The oxygen-evolving complex of Photosystem II oxidizes water 464
Cytochrome b6f links Photosystems I and II 466
A second photooxidation occurs at Photosystem I 467
Chemiosmosis provides the free energy for ATP synthesis 469
16.3 Carbon Fixation 471
Rubisco catalyzes CO2 fixation 471
The Calvin cycle rearranges sugar molecules 472
Box 16.A The C4 Pathway 473
The availability of light regulates carbon fixation 475
Calvin cycle products are used to synthesize sucrose and starch 476
17 Lipid Metabolism 483
17.1 Lipid Transport 483
17.2 Fatty Acid Oxidation 486
Fatty acids are activated before they are degraded 487
Each round of β oxidation has four reactions 488
Degradation of unsaturated fatty acids requires isomerization and reduction 491
Oxidation of odd-chain fatty acids yields propionyl-CoA 492
Some fatty acid oxidation occurs in peroxisomes 494
17.3 Fatty Acid Synthesis 495
Acetyl-CoA carboxylase catalyzes the first step of fatty acid synthesis 496
Fatty acid synthase catalyzes seven reactions 497
Other enzymes elongate and desaturate newly synthesized fatty acids 500
Box 17.A Fats, Diet, and Heart Disease 500
Fatty acid synthesis can be activated and inhibited 501
Box 17.B Inhibitors of Fatty Acid Synthesis 502
Acetyl-CoA can be converted to ketone bodies 503
17.4 Synthesis of Other Lipids 505
Triacylglycerols and phospholipids are built from acyl-CoA groups 505
Cholesterol synthesis begins with acetyl-CoA 508
A summary of lipid metabolism 510
18 Nitrogen Metabolism 518
18.1 Nitrogen Fixation and Assimilation 518
Nitrogenase converts N2 to NH3 519
Ammonia is assimilated by glutamine synthetase and glutamate synthase 519
Transamination moves amino groups between compounds 521
Box 18.A Transaminases in the Clinic 523
18.2 Amino Acid Biosynthesis 523
Several amino acids are easily synthesized from common metabolites 524
Amino acids with sulfur, branched chains, or aromatic groups are more difficult to synthesize 526
Box 18.B Homocysteine, Methionine, and One-Carbon Chemistry 527
Box 18.C Glyphosate, the Most Popular Herbicide 528
Amino acids are the precursors of some signaling molecules 530
Box 18.D Nitric Oxide 531
18.3 Amino Acid Catabolism 532
Amino acids are glucogenic, ketogenic, or both 532
Box 18.E Diseases of Amino Acid Metabolism 535
18.4 Nitrogen Disposal: The Urea Cycle 536
Glutamate supplies nitrogen to the urea cycle 537
The urea cycle consists of four reactions 538
18.5 Nucleotide Metabolism 540
Purine nucleotide synthesis yields IMP and then AMP and GMP 541
Pyrimidine nucleotide synthesis yields UTP and CTP 542
Ribonucleotide reductase converts ribonucleotides to deoxyribonucleotides 543
Thymidine nucleotides are produced by methylation 544
Nucleotide degradation produces urate or amino acids 545
19 Regulation of Mammalian Fuel Metabolism 555
19.1 Integration of Fuel Metabolism 555
Organs are specialized for different functions 556
Metabolites travel between organs 557
Box 19.A The Intestinal Microbiota Contribute to Metabolism 558
19.2 Hormonal Control of Fuel Metabolism 560
Insulin is released in response to glucose 560
Insulin promotes fuel use and storage 561
mTOR responds to insulin signaling 563
Glucagon and epinephrine trigger fuel mobilization 564
Additional hormones influence fuel metabolism 565
AMP-dependent protein kinase acts as a fuel sensor 566
Fuel metabolism is also controlled by redox balance and oxygen 566
19.3 Disorders of Fuel Metabolism 568
The body generates glucose and ketone bodies during starvation 568
Box 19.B Marasmus and Kwashiorkor 568
Obesity has multiple causes 569
Diabetes is characterized by hyperglycemia 570
Obesity, diabetes, and cardiovascular disease are linked 572
19.4 Clinical Connection: Cancer Metabolism 573
Aerobic glycolysis supports biosynthesis 573
Cancer cells consume large amounts of glutamine 574
Part 4 Genetic Information
20 DNA Replication and Repair 582
20.1 The DNA Replication Machinery 582
Replication occurs in factories 583
Helicases convert double-stranded DNA to single-stranded DNA 584
DNA polymerase faces two problems 585
DNA polymerases share a common structure and mechanism 587
DNA polymerase proofreads newly synthesized DNA 589
An RNase and a ligase are required to complete the lagging strand 590
20.2 Telomeres 593
Telomerase extends chromosomes 594
Box 20.A HIV Reverse Transcriptase 595
Is telomerase activity linked to cell immortality? 596
20.3 DNA Damage and Repair 596
DNA damage is unavoidable 597
Repair enzymes restore some types of damaged DNA 598
Base excision repair corrects the most frequent DNA lesions 598
Nucleotide excision repair targets the second most common form of DNA damage 599
Double-strand breaks can be repaired by joining the ends 601
Recombination also restores broken DNA molecules 601
Box 20.B Gene Editing with CRISPR 602
20.4 Clinical Connection: Cancer as a Genetic Disease 604
Tumor growth depends on multiple events 605
DNA repair pathways are closely linked to cancer 605
20.5 DNA Packaging 607
DNA is negatively supercoiled 607
Topoisomerases alter DNA supercoiling 608
Eukaryotic DNA is packaged in nucleosomes 610
20.6 Tools and Techniques: Manipulating DNA 611
Cutting and pasting generates recombinant DNA 612
The polymerase chain reaction amplifies DNA 614
DNA sequencing uses DNA polymerase to make a complementary strand 615
21 Transcription and RNA 627
21.1 Initiating Transcription 627
What is a gene? 628
DNA packaging affects transcription 628
DNA also undergoes covalent modification 631
Transcription begins at promoters 631
Transcription factors recognize eukaryotic promoters 633
Mediator integrates multiple regulatory signals 634
Box 21.A DNA-Binding Proteins 635
Prokaryotic operons allow coordinated gene expression 636
21.2 RNA Polymerase 638
RNA polymerases have a common structure and mechanism 639
Box 21.B RNA-Dependent RNA Polymerase 640
RNA polymerase is a processive enzyme 641
Transcription elongation requires changes in RNA polymerase 642
Transcription is terminated in several ways 644
21.3 RNA Processing 645
Eukaryotic mRNAs receive a 5' cap and a 3' poly(A) tail 645
Splicing removes introns from eukaryotic RNA 646
mRNA turnover and RNA interference limit gene expression 649
Box 21.C The Nuclear Pore Complex 649
rRNA and tRNA processing includes the addition, deletion, and modification of nucleotides 652
RNAs have extensive secondary structure 653
22 Protein Synthesis 663
22.1 tRNA and the Genetic Code 663
The genetic code is redundant 664
tRNAs have a common structure 665
tRNA aminoacylation consumes ATP 666
Editing increases the accuracy of aminoacylation 667
tRNA anticodons pair with mRNA codons 668
Box 22.A The Genetic Code Expanded 669
22.2 Ribosome Structure 669
The ribosome is mostly RNA 670
Three tRNAs and one mRNA bind to the ribosome 671
22.3 Translation 673
Initiation requires an initiator tRNA 673
The appropriate tRNAs are delivered to the ribosome during elongation 675
The peptidyl transferase active site catalyzes peptide bond formation 677
Box 22.B Antibiotic Inhibitors of Protein Synthesis 679
Release factors mediate translation termination 680
Translation is efficient and dynamic 681
22.4 Post-Translational Events 683
Chaperones promote protein folding 684
The signal recognition particle targets some proteins for membrane translocation 685
Many proteins undergo covalent modification 687
Glossary G-1
Odd-Numbered Solutions S-1
Index i-1
