Biochemistry:
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| Format: | Buch |
| Sprache: | Englisch |
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Austin ; Boston ; New York ; Plymouth
Macmillan Learning
[2023]
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| Ausgabe: | Tenth edition |
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| Links: | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034156360&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| Umfang: | xxxvii, 1001, A31, I44 Seiten Illustrationen, Diagramme |
| ISBN: | 9781319498504 9781319333621 9781319498405 |
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BRIEF 1 Biochemistry in Space and Time 1 2 Protein Composition and Structure 33 з Binding and Molecular Recognition 68 4 Protein Methods 100 5 Enzymes: Core Concepts and Kinetics 141 6 Enzyme Catalytic Strategies 179 7 Enzyme Regulatory Strategies 210 8 DNA, RNA, and the Flow of Genetic information 236 9 Nucleic Acid Methods 264 10 Exploring Evolution and Bioinformatics 301 11 Carbohydrates and Glycoproteins 324 12 Lipids and Biological Membranes 352 13 Membrane Channels and Pumps 381 14 Signal-Transduction Pathways 412 15 Metabolism: Basic Concepts and Themes 446 16 Glycolysis and Gluconeogenesis 472 17 Pyruvate Dehydrogenase and the Citric Acid Cycle 515 18 Oxidative Phosphorylation 542 19 Phototrophy and the Light Reactions of Photosynthesis 585 20 The Calvin-Benson Cycle and the Pentose Phosphate Pathway 610 21 Glycogen Metabolism 640 22 Fatty Acid and Triacylglycerol Metabolism 665 23 Protein Turnover and Amino Acid Catabolism 701 24 integration of Energy Metabolism 732 25 Biosynthesis of Amino Acids 763 26 Nucleotide Biosynthesis 791 27 Biosynthesis of Membrane Lipids and Steroids 814 28 DNA Replication, Repair, and Recombination 845 29 RNA Functions, Biosynthesis, and Processing 879 ЗО Protein Biosynthesis 916 31 Control of Gene Expression 949 32 Principles of Drug Discovery and Development 977 ХХІѴ PREFACE ACKNOWLEDGMENTS . ABOUT THE AUTHORS ХХХІѴ ХХХѴІІ CHAPTER 1 Biochemistry in Space and Time 1 1.1 Biochemical Unity Underlies Biological Diversity 2 1.2 DNA illustrates the interplay Between Form and Function . 4 DNA is constructed from four building blocks TWo
single strands of DNA combine to form a double helix DNA structure explains heredity and the storage of information 4 5 6 1.3 Concepts from Chemistry Explain the Properties of Biological Molecules 6 ., The formation of the DNA double helix is a key example 6 The double helix can form from its component strands б Atoms and molecules undergo random motions that help define the timescales for biochemical interactions 7 Covalent bonds and noncovalent interactions are import ant for the structure and stability of biological molecules 7 The formation of DNA's double helix is an expression of the rules of chemistry 11 The laws of thermodynamics govern the behavior of biochemical systems 12 By releasing heat, the formation of the double helix obeys the Second Law of Thermodynamics 14 Double-helix formation can be monitored one molecule at a time 15 Acid-base reactions are central in many biochemical processes 17 Acid-base reactions can disrupt the double helix 17 Buffers regulate pH in organisms and in the laboratory 19 EXAMPLE Applying the Henderson-Hasselbalch Equation 20 1.4 DNA Sequencing is Transforming Biochemistry, Medicine, and Other Fields 21 Genome sequencing has become remarkably fast and inexpensive Characterization of genetic variation between individuals is powerful for many applications The most important function of genomic sequences is to encode proteins Comparing genomes offers great insights into 1.5 Biochemistry is an Endeavor 21 22 25 Human 27
vil CONTENTS CHAPTER 2 Protein Composition and Structure 33 Binding is a dynamic process involving association and dissociation 72 73 3.2 Myoglobin Binds and Stores oxygen 2.1 Several Properties of Protein structure Are Key to Their Functional Versatility 34 2.2 Proteins Are Built from a Repertoire of 20 Amino Acids 35 The diversity of amino acids arises from the different side chains Biochemists postulate several reasons why this set of amino acids is conserved across all species 2.3 Primary Structure: Amino Acids Are Linked by Peptide Bonds to Form Polypeptide Chains 36 40 41 Proteins have unique amino acid sequences specified by genes Polypeptide chains are flexible yet conformationally restricted 44 2.4 Secondary Structure: Polypeptide Chains Can Fold Into Regular Structures 46 The alpha helix is a coiled structure stabilized by intrachain hydrogen bonds SCIENTIST PROFILE Herman Branson Beta sheets are stabilized by hydrogen bonding between polypeptide strands Polypeptide chains can change direction by making reverse turns and loops 2.5 Tertiary Structure: Proteins Can Fold Into Globular or Fibrous Structures Globular proteins form tightly packed structures Fibrous proteins form extended structures that provide support for cells and tissues 43 46 46 48 50 50 51 53 2.6 Quaternary Structure: Polypeptide Chains Can Assemble Into Multisubunit Structures 55 2.7 The Amino Acid Sequence of a Protein Determines Its Three-Dimensional Structure 55 Amino acids have different propensities for forming a helices, ß sheets, and turns Protein folding is a highly cooperative process
Proteins fold by progressive stabilization of intermediates rather than by random search Prediction of three-dimensional structure from sequence remains a great challenge ■eft. Protein misfolding and aggregation are associated ™ with some neurological diseases Posttranslational modifications confer new capabilities to proteins 57 59 3.1 Binding Is a Fundamental Process in Biochemistry Binding depends on the concentrations of the binding partners Proteins can selectively bind certain small molecules 3.4 The immune System Depends on Key Binding Proteins The innate immune system recognizes molecules characteristic of pathogens Antibodies bind specific molecules through specific hypervariable loops Antibodies possess distinct antigen-binding and effector units Recombination events equip the adaptive immune system with millions of unique antibodies Major-histocompatibility-complex proteins present peptide antigens on cell surfaces for recognition by T-cell receptors 3.5 Quantitative Terms Can Describe Binding Propensity 61 SCIENTIST PROFILE Pamela Bjorkman 63 74 74 75 Human hemoglobin is an assembly of four myoglobin-like subunits Hemoglobin binds oxygen cooperatively Oxygen binding markedly changes the quaternary structure of hemoglobin Hemoglobin cooperativity can be potentially explained by several models Structural changes at the heme groups are transmitted to the cqßj-cqßj interface 2,3-Bisphosphoglycerate in red blood cells is crucial in determining the oxygen affinity of hemoglobin Hydrogen ions and carbon dioxide promote the release of oxygen •eft. Mutations in genes
encoding hemoglobin subunits ™ can result in disease Dissociation constants are useful in describing binding reactions quantitatively 62 73 73 3.3 Hemoglobin is an Efficient Oxygen Carrier 59 75 76 77 78 79 80 81 83 84 84 86 88 89 89 91 example Determining the Fraction of Bound Receptors 91 91 92 Specificity can be quantified by comparing dissociation constants Kinetic parameters can also describe binding processes 93 94 CHAPTER 4 CHAPTER 3 Binding and Molecular Recognition More myoglobin binds oxygen as the oxygen partial pressure is increased A bond is formed between oxygen and iron in heme The structure of myoglobin prevents the release of reactive oxygen species Compared with model compounds, myoglobin discriminates between oxygen and carbon monoxide 68 69 69 70 Protein Methods 4.1 The Purification of Proteins is an Essential First Step in understanding Their Function The assay. How do we recognize the protein we are looking for? Proteins must be released from the cell to be purified 100 101 101 101
vill CONTENTS Proteins can be purified according to solubility, size, charge, and binding affinity Proteins can be separated by gel electrophoresis and displayed A protein purification scheme can be quantitatively evaluated 102 105 110 111 112 4.2 immunology Provides important Techniques for investigating Proteins 112 Antibodies to specific proteins can be generated Monoclonal antibodies with virtually any desired specificity can be readily prepared Proteins can be detected and quantified by using an enzyme-linked immunosorbent assay Western blotting permits the detection of proteins separated by gel electrophoresis Co-immunoprecipitation enables the identification of binding partners of a protein Fluorescent markers make the visualization of proteins in the cell possible 112 113 114 116 116 117 118 for the Identification of Peptides and Proteins Peptides can be sequenced by mass spectrometry 120 Proteins can be specifically cleaved into small peptides to facilitate analysis 121 Genomic and proteomic methods are complementary approaches to deducing protein structure and function 123 The amino acid sequence of a protein provides valuable information 123 Individual proteins can be identified by mass spectrometry 124 The proteome is the functional representation of the genome 125 4.4 Peptides Can Be Synthesized by Automated 126 4.5 Three-Dimensional Protein Structures Can Be Determined Experimentally X-ray crystallography reveals three-dimensional structure in atomic detail 144 The free-energy change provides information about the spontaneity but not the rate of a reaction The
standard free-energy change of a reaction is related to the equilibrium constant 145 145 EXAMPLE Calculating and Comparing AG°' and AG 146 147 Enzymes alter only the reaction rate and not the reaction equilibrium 148 5.3 Enzymes Accelerate Reactions by Facilitating the Formation of the Transition State The formation óf an enzyme-substrate complex is the first step in enzymatic catalysis The active sites of enzymes have some common ՜ features The binding energy between enzyme and substrate is important for catalysis Because the transition state collapses randomly, the activation energies determine the accumulation of either product or substrate 148 149 150 151 151 5.4 The Michaelis-Menten Model Accounts for 4.3 Mass Spectrometry is a Powerful Technique Solid-Phase Methods 144 5.2 Gibbs Free Energy Is a Useful Thermodynamic Function for Understanding Enzymes 109 EXAMPLE Calculating the Effectiveness of Protein Purification Ultracentrifugation is valuable for separating biomolecules and determining their masses Recombinant DNA technology can make protein purification easier Many enzymes require cofactors for activity Enzymes can transform energy from one form into another 129 129 SCIENTIST PROFILE Rosalind Franklin 129 Nuclear magnetic resonance spectroscopy can reveal the structures of proteins in solution 132 Cryo-electron microscopy can be used to determine the structures of large proteins and macromolecular complexes 135 the Kinetic Properties of Many Enzymes Kinetics is the study of reaction rates The steady-state assumption aids a description of enzyme kinetics The
Michaelis-Menten model explains many observations of enzyme kinetics The Michaelis-Menten equation describes the relationship between initial velocity and substrate concentration scientist profile Maud Menten EXAMPLE Applying the Michaelis-Menten Equation Variations in KM can have physiological Ψ consequences KM and Ѵтах values can be determined by several means KM and kcat values are important enzyme characteristics kcat/KM is a measure of catalytic efficiency Most biochemical reactions include multiple substrates Allosteric enzymes often do not obey Michaelis-Menten kinetics Temperature affects enzymatic activity 151 152 152 153 153 154 155 156 156 156 158 159 161 161 5.5 Enzymes Can Be Studied One Molecule at a Time 162 Single-molecule kinetics confirm results obtained from ensemble studies Single-molecule studies continue to reveal new information about enzyme molecular dynamics 163 165 5.6 Enzymes Can Be Inhibited by Specific Molecules 165 CHAPTER 5 Enzymes: Core Concepts and Kinetics 141 5.1 Enzymes Are Powerful and Highly Specific Catalysts 142 Most enzymes are classified by the types of reactions they catalyze 143 The different types of reversible inhibitors are kinetically distinguishable 166 Transition-state analogs are potent competitive inhibitors 169 Irreversible inhibitors can be used to map the active site 169 171 EXAMPLE Determining inhibitor туре from Data Penicillin irreversibly inactivates a key enzyme in W bacterial cell-wall synthesis 172
Ix CONTENTS CHAPTER 6 Enzyme Catalytic Strategies 179 6.1 Enzymes Use a Core Set of Catalytic Strategies 180 6.2 Proteases Facilitate a Fundamentally Difficult Reaction 180 Chymotrypsin possesses a highly reactive serine residue 181 Chymotrypsin action proceeds in two steps linked by a covalently bound intermediate 182 Serine is part of a catalytic triad that also includes histidine and aspartate 183 Catalytic triads are found in other hydrolytic enzymes 186 Scientists have dissected the catalytic triad using site-directed mutagenesis 187 Some proteases cleave peptides at other locations besides serine residues 188 f Protease inhibitors are important drugs 189 6.3 Carbonic Anhydrases Make a Fast Reaction Faster 190 Carbonic anhydrase contains a bound zinc ion essential for catalytic activity 190 Catalysis involves zinc activation of a water molecule 191 Rapid regeneration of the active form of carbonic anhydrase depends on proton availability 192 6.4 Restriction Enzymes Catalyze Highly Specific DNA-Cleavage Reactions 194 Cleavage is by direct displacement of З'-oxygen from phosphorus by magnesium-activated water Restriction enzymes require magnesium for catalytic activity The complete catalytic apparatus is assembled only within complexes of cognate DNA molecules, ensuring specificity Host-cell DNA is protected by the addition of methyl groups to specific bases 218 Kinases and phosphatases control the extent of protein phosphorylation Phosphorylation is a highly effective means of regulating the activities of target proteins Cyclic AMP activates protein kinase A by altering
the quaternary structure •efe Mutations in protein kinase A can cause W Cushing’s syndrome The phosphorylation states of the proteome can be measured 7.4 Many Enzymes Are Activated by Specific Proteolytic cleavage 219 221 221 222 223 223 Chymotrypsinogen is activated by specific cleavage of a single peptide bond Proteolytic activation of chymotrypsinogen leads to the formation of a substrate-binding site The generation of trypsin from trypsinogen leads to the activation of other zymogens Some proteolytic enzymes have specific inhibitors 196 Prothrombin must bind to Ca2+ to be converted to thrombin Fibrinogen is converted by thrombin into a fibrin clot Vitamin К is required for the formation of γ-carboxyglutamate The clotting process must be precisely regulated 197 200 224 225 226 226 229 229 231 231 CHAPTER 8 CHAPTER 7 Allosteric Regulation Enables Control of Metabolic Pathways 7.3 Covalent Modification Is a Means of Regulating Enzyme Activity 7.5 Enzymatic Cascades Allow Rapid Responses Such as Blood Clotting 228 ATP hydrolysis proceeds by the attack of water on the gamma phosphoryl group 201 Formation of the transition state for ATP hydrolysis is associated with a substantial conformational change 202 The altered conformation of myosin persists for a substantial period of time 203 Actin forms filaments along which myosin can move 204 7.1 7.2 isozymes Provide a Means of Regulation Specific to Distinct Tissues and Developmental Stages 217 194 6.5 Molecular Motor Proteins Harness Changes in Enzyme Conformation to Couple ATP Hydrolysis to Mechanical Work 200 Enzyme Regulatory
Strategies ATCase consists of separable catalytic and regulatory subunits 212 Allosteric interactions in ATCase are mediated by large changes in quaternary structure 212 Allosteric regulators modulate the T-to-R equilibrium 216 210 211 Many allosterically regulated enzymes do not follow Michaelis-Menten kinetics 212 DNA, RNA, and the Flow of Genetic Information 236 8.1 A Nucleic Acid Consists of Four Kinds of Bases Linked to a Sugar-Phosphate Backbone 237 RNA and DNA differ in the sugar component and one of the bases 237 Nucleotides are the monomeric units of nucleic acids 238 DNA molecules are very long and have directionality 239 8.2 A Pair of Nucleic Acid Strands with Complementary Sequences Can Form a Double-Helical Structure 240 The double helix is stabilized by hydrogen bonds and van der Waals interactions 240 DNA can assume a variety of structural forms 242
x CONTENTS The major and minor grooves are lined by sequence specific hydrogen-bonding groups Some DNA molecules are circular and supercoiled Single-stranded nucleic acids can adopt elaborate structures 8.3 The Double Helix Facilitates the Accurate Transmission of Hereditary information 244 246 Differences in DNA density established the validity of the semiconservative replication hypothesis The double helix can be reversibly melted 8.4 DNA is Replicated by Polymerases That Take instructions from Templates 243 244 246 247 248 DNA polymerase catalyzes phosphodiester-bridge formation The genes of some viruses are made of RNA 248 249 8.5 Gene Expression Is the Transformation of DNA Information into Functional Molecules 250 Several kinds of RNA play key roles in gene expression All cellular RNA is synthesized by RNA polymerases RNA polymerases take instructions from DNA templates Transcription begins near promoter sites and ends at terminator sites TYansfer RNAs are the adaptor molecules in protein synthesis 8.6 Amino Acids Are Encoded by Groups of Three Bases Starting from a Fixed Point 250 251 252 253 254 255 Major features of the genetic code 255 SCIENTIST PROFILE Har Gobind Khorana 256 Messenger RNA contains start and stop signals for protein synthesis The genetic code is nearly universal 8.7 Most Eukaryotic Genes Are Mosaics of Introns and Exons 257 258 258 RNA processing generates mature RNA Many exons encode protein domains 258 259 Ψ The tools for recombinant DNA technology have been used to identify disease-causing mutations 271 9.2 Recombinant DNA Technology Has
Revolutionized All Aspects Of Biology Restriction enzymes and DNA ligase are key tools · in forming recombinant DNA molecules Plasmids and λ phage are choice vectors for DNA cloning in bacteria Specific genes can be cloned from digests of genomic DNA Complementary DNA prepared from mRNA can be expressed in host cells Proteins with new functions can be created through directed changes in DNA 272 272 274 277 278 279 9.3 Complete Genomes Have Been Sequenced and Analyzed 282 The genomes of organisms ranging from bacteria - to multicellular eukaryotes have been sequenced The sequence of the human genome has been completed Next-generation sequencing methods enable the rapid determination of a complete genome sequence Comparative genomics is a powerful research tool 282 283 284 286 9.4 Eukaryotic Genes Can Be Quantitated and Manipulated with Considerable Precision 287 Gene-expression levels can be comprehensively examined 287 New genes inserted into eukaryotic cells can be efficiently expressed 289 Tïansgenic animals harbor and express genes introduced into their germ lines 290 Gene disruption and genome editing provide clues to gene function and opportunities for new therapies 290 RNA interference enables disruption of gene expression and presents new therapeutic opportunities 294 SCIENTIST profile Emmanuelle Charpentier and Jennifer Doudna Foreign DNA can be introduced into plants 294 295 CHAPTER 9 Nucleic Add Methods 264 CHAPTER 10 Exploring Evolution and Bioinformatics 9.1 The Exploration of Genes Relies on Key Tools Restriction enzymes split DNA into specific fragments
Restriction fragments can be separated by gel electrophoresis and visualized DNA can be sequenced by controlled termination of replication DNA probes and genes can be synthesized by automated solid-phase methods Selected DNA sequences can be greatly amplified by the polymerase chain reaction PCR is a powerful technique in medical diagnostics, forensics, and studies of molecular evolution 301 265 265 266 267 268 269 271 10.1 Homologs Are Descended from a Common Ancestor and Can Be Detected by Sequence Alignments 302 Orthologs and paralogs are two different classes of homologous proteins 302 Statistical analysis of sequence alignments can detect homology 302 The statistical significance of alignments can be estimated by shuffling 305 Distant evolutionary relationships can be detected through the use of substitution matrices 305 Databases can be searched to identify homologous sequences 308
CONTENTS 10.2 Examination of Three-Dimensional Structure Enhances Our Understanding of Evolutionary Relationships 310 Tertiary structure is more conserved than primary structure Knowledge of three-dimensional structures can aid in the evaluation of sequence alignments Repeated motifs can be detected by aligning sequences with themselves Convergent evolution illustrates common solutions to biochemical challenges Comparison of RNA sequences can be a source of insight into RNA secondary structures 310 311 311 313 314 EXAMPLE interpreting an RNA Alignment 315 10.3 Evolutionary Trees Can Be Constructed on the Basis of Sequence information 316 Evolutionary trees can be calibrated using fossil record data Horizontal gene transfer events may explain unexpected branches of the evolutionary tree 316 317 SCIENTIST PROFILE Russell Doolittle 318 10.4 Modern Techniques Make the Experimental Exploration of Evolution Possible 318 Ancient DNA can sometimes be amplified and sequenced Molecular evolution can be examined experimentally 318 Cellulose is the main structural polysaccharide of plants 335 Chitin is the main structural polysaccharide of fungi and arthropods 336 Chitin can be processed to a molecule with a variety of uses 337 11.3 Carbohydrates Can Be Linked to Proteins to Form Glycoproteins 337 Carbohydrates can be linked to proteins through asparagine (N-linked) or through serine or threonine (О-linked) residues 338 ^^ The glycoprotein erythropoietin is a vital hormone 339 Glycosylation functions in nutrient sensing 339 Proteoglycans have important structural roles 339
Proteoglycans are important components of cartilage 340 Mucins are glycoprotein components of mucus 341 Protein glycosylation takes place in the lumen of the endoplasmic reticulum and in the Golgi complex 341 Specific enzymes are responsible for oligosaccharide assembly · 342 Blood groups are based on protein glycosylation patterns 343 ■eft. Errors in glycosylation can result in pathological Ψ conditions 344 Biochemists use several techniques to analyze the oligosaccharide components of glycoproteins 345 11.4 Lectins Are Specific Carbohydrate-Binding Proteins 319 CHAPTER 11 Carbohydrates and Glycoproteins 324 346 Lectins promote interactions between celis and within cells Lectins are organized into two large classes Influenza virus binds to sialic acid residues SCIENTIST PROFILE Carolyn Bertozzi 11.1 Monosaccharides Are the Simplest Carbohydrates 347 Lipids and Biological Membranes 352 325 12.1 Fatty Acids Are Key Constituents of Lipids 327 329 330 330 331 332 11.2 Monosaccharides Are Linked to Form Complex Carbohydrates 346 346 347 CHAPTER 12 325 There are many monosaccharides but they are structurally similar Most monosaccharides exist as interchanging cyclic forms Pyranose and furanose rings can assume different conformations D-Glucose is an important fuel for most organisms Glucose is a reducing sugar and reacts nonenzymatically with hemoglobin Monosaccharides are joined to alcohols and amines through glycosidic linkages by specific enzymes Phosphorylated sugars are key intermediates in metabolism Xl 333 Sucrose, lactose, and maltose are common disaccharides 333 Maltase
inhibitors can help to maintain blood glucose homeostasis 334 Human milk oligosaccharides protect newborns from infection 335 Glycogen and starch are storage polysaccharides of glucose 335 Fatty acid names are based on their parent hydrocarbons Chain length and degree of unsaturation affect fatty acid properties 353 353 354 12.2 Biological Membranes Are Composed of Three Common Types of Membrane Lipids355 Phospholipids are the major class of membrane lipids Glycolipids include carbohydrate moieties Cholesterol is a lipid based on a steroid nucleus 355 357 357 SCIENTIST PROFILE Marie Μ. Daly 357 Archaeal membranes are built from ether lipids with branched chains 358 A membrane lipid is an amphipathic molecule containing a hydrophilic and a hydrophobic moiety 358 12.3 Phospholipids and Glycolipids Readily Form Bimolecular Sheets in Aqueous Media Lipid vesicles can be formed from phospholipids Lipid bilayers are highly impermeable to ions and most polar molecules 359 360 361
xli CONTENTS 12.4 Proteins Carry Out Most Membrane Processes Proteins associate with the lipid bilayer in a variety of ways Proteins interact with membranes in a variety of ways Some proteins associate with membranes through covalently attached hydrophobic groups Transmembrane helices can be accurately predicted from amino acid sequences 363 SCIENTIST PROFILE Baldomero Olivera 363 367 369 370 370 372 373 EXAMPLE Calculating Equilibrium Potentials CHAPTER 13 Membrane Channels and Pumps 381 EXAMPLE Calculating the Energetic Cost of Ion Transport 38Յ 13.5 Gap Junctions Allow ions and Small Molecules to Flow Between Communicating Cells , 398 399 400 402 406 13.6 Specific Channels increase the Permeability of Some Membranes to water 407 CHAPTER 14 412 Hydrolysis to Actively Transport ions and Molecules Across Membranes 384 P-type ATPases couple phosphorylation and conformational changes to pump calcium ions across membranes 384 4ft. Digoxin specifically inhibits the Na+-K+ pump by Ψ blocking its dephosphorylation 387 P-type ATPases are evolutionarily conserved and play a wide range of roles 387 4ft Multidrug resistance highlights a family of Ψ membrane pumps with ATP-binding cassette domains 388 390 13.4 Specific Channels Can Rapidly Transport ions 392 Action potentials are mediated by transient changes in Na+ and K+ permeability 392 14.1 Many Signal-Transduction Pathways Share Common Themes 413 Signal transduction depends on molecular circuits 413 14.2 Epinephrine Signaling: Heterotrimeric G Proteins Transmit Signals and Reset Themselves 13.2 Two Families of Membrane Proteins
Use ATP Across Membranes 398 382 Many molecules require protein transporters to cross membranes 382 Free energy stored in concentration gradients can be quantified 382 13.3 Lactose Permease is an Archetype of Secondary Transporters That Use One Concentration Gradient to Power the Formation of Another 395 403 Signal-Transduction Pathways 13.1 The Transport of Molecules Across a Membrane May Be Active or Passive 394 Disruption of ion channels by mutations or chemicals can be potentially life-threatening 404 Hyperpolarization-activated ion channels enable pacemaker activity in the heart 405 12.6 Prokaryotes and Eukaryotes Differ in Their Use of Biological Membranes 373 Eukaryotic cells contain compartments bounded by internal membranes 374 Membrane budding and fusion are highly controlled processes 375 393 395 The structure of the potassium ion channel reveals the basis of ion specificity The structure of the potassium ion channel explains its rapid rate of transport Voltage gating requires substantial conformational changes in specific ion-channel domains A channel can be inactivated by occlusion of the pore: the ball-and-chain model The acetylcholine receptor is an archetype for ligand-gated ion channels Action potentials integrate the activities of several ion channels working in concert 367 12.5 Lipids and Many Membrane Proteins Diffuse Rapidly in the Plane of the Membrane The fluid mosaic model allows lateral movement but not rotation through the membrane Membrane fluidity is controlled by fatty acid composition and cholesterol content Lipid rafts are highly dynamic
complexes formed between cholesterol and specific lipids All biological membranes are asymmetric Patch-clamp conductance measurements reveal the activities of single channels The structure of a potassium ion channel is an archetype for many ion-channel structures 362 414 Ligand binding to 7TM receptors leads to the activation of heterotrimeric G proteins 415 Activated G proteins transmit signals by binding to other proteins 418 Cyclic AMP stimulates the phosphorylation of many target proteins by activating protein kinase A 418 G proteins spontaneously reset themselves through GTP hydrolysis 419 Some 7TM receptors activate the phosphoinositide cascade 420 Calcium ion is a widely used second messenger 421 Calcium ion often activates the regulatory protein calmodulin 423 Some receptors signal through G proteins that inhibit rather than stimulate adenylate cyclase 423 G-protein βγ-dimers can also directly participate in signaling 424 7TM receptors trigger signaling through G proteins in many other cell types 424 SCIENTIST PROFILE Eva Neer 425
ХІІІ CONTENTS 14.3 insulin Signaling: Phosphorylation Cascades Are Central to Many Signal-Transduction Processes 425 The insulin receptor is a protein kinase that is autoinhibited prior to insulin binding 426 Insulin binding results in the cross-phosphorylation and activation of the insulin receptor 427 The activated insulin-receptor kinase initiates a kinase cascade 428 Insulin signaling is terminated by the action of phosphatases 430 14.4 Epidermal Growth Factor: Receptor Dimerization Can Drive Signaling 431 The EGF receptor undergoes phosphorylation of its carboxyl-terminal tail 432 EGF signaling leads to the activation of Ras, a small G protein 432 Activated Ras initiates a protein kinase cascade 432 EGF signaling is terminated by protein phosphatases and the intrinsic GTPase activity of Ras 433 14.5 Defects in Signal-Transduction Pathways Can Lead to Cancer and Other Diseases 433 Monoclonal antibodies can be used to inhibit signal transduction pathways activated in tumors 434 Protein kinase inhibitors can be effective anticancer drugs 435 14.6 Sensory Systems Are Based on Specialized Signal-iransduction Pathways 435 A huge family of 7TM receptors detect a wide variety of organic compounds 436 Vision relies on a specialized 7TM receptor to signal in response to absorbed light 437 Light absorption induces a specific isomerization of bound 11-cis-retinal 439 Color vision is mediated by three cone receptors that are homologs of rhodopsin 440 Hearing depends on hair cells that use mechanosensitive ion channels to detect tiny motions 440 Comparison of different organisms
yields insights into sensory system evolution 441 CHAPTER 15 Metabolism: Basic Concepts and Themes 446 15.1 Metabolism is Composed of Many Interconnected Reactions 447 Metabolism consists of destructive and constructive reactions that typically yield or require energy 448 A thermodynamically unfavorable reaction can be driven by a favorable reaction 449 15.2 ATP is the Universal Currency of Free Energy in Biological Systems 449 ATP hydrolysis is exergonic 450 ATP hydrolysis drives metabolism by shifting the equilibrium of coupled reactions 451 The high phosphoryl potential of ATP results from structural differences between ATP and its hydrolysis products 452 Phosphoryl-transfer potential is an important form of cellular energy transformation 453 EXAMPLE Calculating AG for a Coupled Reaction under Real Conditions 455 15.3 The Oxidation of Carbon Fuels is an Important Source of Cellular Energy 456 Compounds with high phosphoryl-transfer potential can couple carbon oxidation to ATP synthesis 457 Ion gradients across membranes provide an important form of cellular energy that can be coupled to ATP synthesis 458 Phosphates play a prominent role in biochemical processes 458 Energy from food is extracted in three stages 459 15.4 Metabolic Pathways Contain Many Recurring Motifs 460 Activated carriers exemplify the modular structure and economy of metabolism 460 Many activated carriers are derived from vitamins 463 Key reactions are reiterated throughout metabolism 464 Metabolic processes are regulated in three principal ways 467 CHAPTER 16 Glycolysis and Gluconeogenesis 472 16.1
Glycolysis Is an Energy-Conversion Pathway in Most Organisms 473 Glucose is generated from dietary carbohydrates 473 A family of transporters enables glucose to enter and leave animal cells 474 16.2 Glycolysis Can Be Divided into Two Parts 474 Stage 1 begins: Hexokinase traps glucose in the cell and begins glycolysis 476 Fructose 1,6-bisphosphate is generated from glucose 6-phosphate 477 The six-carbon sugar is cleaved into two three-carbon fragments 478 Mechanism: Triose phosphate isomerase salvages a three-carbon fragment 478 Stage 2 begins: The oxidation of an aldehyde powers the formation of a compound with high phosphoryl-transfer potential 480 Mechanism: Phosphorylation is coupled to the oxidation of glyceraldehyde 3-phosphate by a thioester intermediate 482 ATP is formed by phosphoryl transfer from 1,3-bisphosphoglycerate 482 Additional ATP is generated with the formation of pyruvate 484 Two ATP molecules are formed in the conversion of glucose into pyruvate 485 NAD+ is regenerated from the metabolism of pyruvate 486
xlv CONTENTS Fermentations provide usable energy in the absence of oxygen Fructose is converted into glycolytic intermediates by fructokinase Galactose is converted into glucose 6-phosphate ■eft֊ Galactose can be highly toxic with a V defective metabolic pathway ■eft. Many adults worldwide are intolerant of milk ™ because they are deficient in lactase 16.3 The Glycolytic Pathway is Tightly Controlled Glycolysis in muscle is regulated to meet the need for ATP The regulation of glycolysis in the liver illustrates the biochemical versatility of the liver The enzymes of glycolysis are physically associated with one another ■aft Aerobic glycolysis is a property of tumor cells 9 and other rapidly growing cells ■aft Cancer and endurance training affect glycolysis ™ in a similar fashion 17.2 The Pyruvate Dehydrogenase Complex Links 488 489 490 491 492 492 493 494 497 497 498 16.4 Glucose Can Be Synthesized from Noncarbohydrate Precursors 499 Gluconeogenesis is not a reversal of glycolysis 499 The conversion of pyruvate into phosphoenolpyruvate begins with the formation of oxaloacetate 501 Oxaloacetate is shuttled into the cytoplasm and converted into phosphoenolpyruvate 502 The conversion of fructose 1,6-bisphosphate into fructose 6-phosphate and orthophosphate is an 503 irreversible step The generation of free glucose occurs only in some 503 tissues and is an important control point Six high-transfer-potential phosphoryl groups are spent in synthesizing glucose from pyruvate 504 Glycolysis to the Citric Acid Cycle Mechanism: The synthesis of acetyl coenzyme A from pyruvate
requires three enzymes and five coenzymes Flexible linkages allow lipoamide to move between different active sites 517 518 520 17.3 The Citric Acid Cycle Oxidizes TWo-Carbon Units Citrate synthase forms citrate from oxaloacetate and the acetyl group from acetyl coenzyme A Mechanism: The mechanism of citrate synthase prevents undesirable reactions Citrate is isomerized into isocitrate Isocitrate is oxidized and decarboxylated to alpha-ketoglutarate Succinyl coenzyme A is formed by the oxidative decarboxylation of alpha-ketoglutarate A compound with high phosphoryl-transfer potential is generated from succinyl coenzyme A Mechanism: Succinyl coenzyme A synthetase transforms types of biochemical energy Oxaloacetate is regenerated by the oxidation of succinate 522 522 523 524 525 526 526 527 SCIENTIST PROFILE Hans Krebs 528 528 The citric acid cycle produces high-transfer-potential electrons, ATP, and CO2 529 17.4 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled The pyruvate dehydrogenase complex is regulated allosterically and by reversible phosphorylation •eft֊ Diabetic neuropathy may be due to inhibition • of the pyruvate dehydrogenase complex The citric acid cycle is regulated at several points 531 531 532 533 16.5 Gluconeogenesis and Glycolysis Are Reciprocally Regulated Glycolysis and gluconeogenesis are regulated by adenosine nucleotides and other metabolic intermediates In mammals, glycolysis and gluconeogenesis in the liver are controlled by hormones sensitive to blood-glucose concentration Substrate cycles amplify metabolic signals and produce
heat Lactate and alanine formed by contracting muscle and peripheral tissues are used by other organs ■gft· Deficiencies in glycolytic or gluconeogenic ™ enzymes are rare genetic disorders SCIENTIST PROFILE Gerty Cori Glycolysis and gluconeogenesis are evolutionarily intertwined 505 Biosynthetic Precursors 505 506 508 508 509 509 511 534 534 535 536 17.6 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate •eft֊ Blocking the glyoxylate cycle may lead to new • treatments for tuberculosis 536 538 CHAPTER 18 542 18.1 Cellular Respiration Drives ATP Formation 515 17.1 The Citric Acid Cycle Harvests High-Energy Electrons The citric acid cycle must be capable of being rapidly replenished ■«ft· The disruption of pyruvate metabolism ™ is the cause of beriberi and poisoning by mercury and arsenic The citric acid cycle likely evolved from preexisting pathways Oxidative Phosphorylation CHAPTER 17 Pyruvate Dehydrogenase and the Citric Acid Cycle 17.5 The Citric Acid Cycle is a Source of 516 by Transferring Electrons to Molecular Oxygen Eukaryotic oxidative phosphorylation takes place in mitochondria 543 543
CONTENTS Mitochondria are the result of an endosymbiotic event 544 545 SCIENTIST PROFILE Lynn Margulis 18.2 Oxidative Phosphorylation Depends on Electron Transfer 545 The electron-transfer potential of an electron is measured as redox potential 545 example Calculating the Standard Free Energy of a Reaction from Reduction Potentials 547 Electron flow from NADH to molecular oxygen powers the formation of a proton gradient 18.3 The Respiratory Chain Consists of Four Complexes: Three Proton Pumps and a Physical Link to the Citric Acid Cycle 548 18.4 A Proton Gradient Powers the Synthesis of ATP 551 552 553 555 19.1 Phototrophy converts Light Energy into Chemical Energy 556 559 560 561 562 Electrons from cytoplasmic NADH enter mitochondria by shuttles 570 The entry of ADP into mitochondria is coupled to the exit of ATP by ATP-ADP translocase 572 The complete oxidation of glucose yields about 30 molecules of ATP 575 577 577 578 579 573 573 579 580 CHAPTER 19 Phototrophy and the Light Reactions Of Photosynthesis 570 18.6 The Regulation of Cellular Respiration Is Governed Primarily by the Need for ATP 574 575 Proton flow through a rotary motor allows bacteria to swim Power transmission by proton gradients is a central motif of bioenergetics 554 The chemiosmotic hypothesis suggested that ATP formation is powered by a proton gradient 562 ATP synthase is composed of a proton-conducting unit and a catalytic unit 564 Proton flow through ATP synthase leads to the release of tightly bound ATP via the binding-change mechanism 565 Rotational catalysis is the world’s smallest molecular motor
567 Proton flow around the c ring powers ATP synthesis 567 ATP synthase and G proteins have several common features 569 18.5 Many Shuttles Allow Movement Across Mitochondrial Membranes The rate of oxidative phosphorylation is determined by the need for ATP ATP synthase can be regulated Regulated uncoupling leads to the generation ofheat Réintroduction of UCP-1 into pigs may be economically valuable Oxidative phosphorylation can be inhibited at many stages New mitochondrial diseases are constantly Ψ being discovered Mitochondria play a key role in apoptosis 18.7 Proton Gradients Generated by Respiratory Chains Drive Many Biochemical Processes579 549 Iron-sulfur clusters are common components of the electron-transport chain The high-potential energy electrons of NADH enter the respiratory chain at NADH-Q oxidoreductase Ubiquinol is the entry point for electrons from FADH2 of flavoproteins Electrons flow from ubiquinol to cytochrome c through Q-cytochrome c oxidoreductase The Q cycle funnels electrons from a two-electron carrier to a one-electron carrier while pumping protons Cytochrome c oxidase catalyzes the reduction of molecular oxygen to water Most of the electron-transport chain is organized into a larger complex called the respirasome Toxic derivatives of molecular oxygen such as superoxide radicals are scavenged by protective enzymes Electrons can be transferred between groups that are not in contact XV 585 586 Photosynthesis comprises light reactions and dark reactions The same biochemical principles govern both respiration and photosynthesis TWo kinds of light
reactions take place in the green plants 587 587 588 19.2 in Eukaryotes, Photosynthesis Takes Place in Chloroplasts 588 The primary events of photosynthesis take place in thylakoid membranes Chloroplasts arose from an endosymbiotic event 588 589 19.3 Light Absorption by Chlorophyll Molecules induces Electron Transfer 589 Transferring electrons allows energy to be captured instead of lost as heat A “special pair” of chlorophylls initiate charge separation A proton gradient across the membrane is established Cyclic electron flow reduces the cytochrome of the reaction center 590 590 592 592 19.4 two Photosystems Generate a Proton Gradient and Reducing Power in Cyanobacteria and Photosynthetic Eukaryotes 593 Photosystem II transfers electrons from water to plastoquinone and generates a proton gradient 593 Photosystem II is comparable to the purple bacterial reaction center 594 Cytochrome ₺ƒ links photosystem II to photosystem I 596 Photosystem I uses light energy to generate reduced ferredoxin, a powerful reductant 597
xvi CONTENTS Ferredoxin-NADP*· reductase converts NADP* into NADPH SCIENTIST PROFILE Peter Mitchell and André Jagendorf 598 599 19.5 A Proton Gradient across the Thylakoid Membrane Drives ATP Synthesis 599 The ATP synthase of chloroplasts closely resembles those of mitochondria and prokaryotes 600 The activity of chloroplast ATP synthase is regulated 601 Cyclic electron flow through photosystem I leads to the production of ATP instead of NADPH 601 The absorption of eight photons yields one O2, two NADPH, and three ATP molecules 602 19.6 Accessory Pigments Funnel Energy into Reaction Centers 602 Resonance energy transfer allows energy to move from the site of initial absorbance to the reaction center Accessory pigments also protect plants from reactive oxygen Increasing the efficiency of photosynthesis will increase crop yields The components of photosynthesis are highly organized Many herbicides inhibit the light reactions of photosynthesis 603 604 604 605 605 19.7 The Ability to Convert Light into Chemical Energy Is Ancient 606 Artificial photosynthetic systems may provide clean, renewable energy Photosensitive proteins are transforming other fields 606 607 CHAPTER 20 The Calvin-Benson Cycle and the Pentose Phosphate Pathway 20.1 The Calvin-Benson Cycle Synthesizes Hexoses from Carbon Dioxide and water Stage 1: Carbon dioxide reacts with ribulose 1,5- bisphosphate to form two molecules of 3-phosphoglycerate SCIENTIST PROFILE Andrew Benson Rubisco activity depends on magnesium and carbamate Rubisco also catalyzes a wasteful oxygenase reaction Stage 2: Hexose phosphates are
made from phosphoglycerate Stage 3: Ribulose 1,5-bisphosphate is regenerated 18 ATP and 12 NADPH molecules are used to bring six carbon dioxides to the level of a hexose Starch and sucrose are the major carbohydrate stores in plants Inspired by the Calvin-Benson cycle, scientists are developing new methods for fixing carbon dioxide 610 611 20.2 The Activity of the Calvin-Benson Cycle Depends on Environmental Conditions 620 Rubisco is activated by light-driven changes in proton and magnesium ion concentrations 621 Thioredoxin plays a key role in regulating the CalvinBenson cycle 621 The C4 pathway of tropical plants and grasses accelerates photosynthesis by concentrating carbon dioxide 622 Crassulacean acid metabolism permits growth in arid ecosystems 624 20.3 The Pentose Phosphate Pathway Generates NADPH and Synthesizes Pentoses 624 Two molecules of NADPH are generated in the conversion of glucose 6-phosphate into ribulose 5-phosphate 626 The pentose phosphate pathway and glycolysis are linked by transketolase and transaldolase 626 TYansketolase and transaldolase stabilize carbanionic intermediates by different mechanisms 628 20.4 The Metabolism of Glucose 6-Phosphate by the Pentose Phosphate Pathway is Coordinated with Glycolysis 631 The rate of the oxidative phase of the pentose phosphate pathway is controlled by the level ofNADP* 631 The flow of glucose 6-phosphate depends on the need for NADPH, ribose 5-phosphate, and ATP 631 The pentose phosphate pathway is required for rapid cell growth 633 The Calvin-Benson cycle and the pentose phosphate pathway are essentially
mirror images of one another 633 20.5 Glucose 6-Phosphate Dehydrogenase Plays a Key Role in Protection Against Reactive Oxygen Species 634 Glucose 6-phosphate dehydrogenase deficiency ” causes a drug-induced hemolytic anemia A deficiency of glucose 6-phosphate dehydrogenase can be protective against malaria Glycogen Metabolism 21.1 Glycogen Metabolism is the Regulated Release and Storage of Glucose in Multiple Tissues 641 612 614 21.2 Glycogen Breakdown Requires the interplay of Several Enzymes 642 618 618 619 635 CHAPTER 21 611 611 615 615 634 Phosphorylase catalyzes the phosphorolytic cleavage of glycogen to release glucose 1-phosphate Mechanism: Pyridoxal phosphate participates in the phosphorolytic cleavage of glycogen Debranching enzyme also is needed for the breakdown of glycogen Phosphoglucomutase converts glucose 1-phosphate into glucose 6-phosphate 640 642 643 645 646
CONTENTS The liver contains glucose 6-phosphatase, a hydrolytic enzyme absent from muscle 646 21.3 Phosphorylase is Regulated by Allosteric interactions and Controlled by Reversible Phosphorylation 647 Liver phosphorylase produces glucose for use by other tissues 647 Muscle phosphorylase is regulated by changes in AMP and ATP concentrations 648 Biochemical characteristics of muscle fiber types differ 649 Phosphorylation promotes the conversion of phosphorylase b to phosphorylase a 650 Phosphorylase kinase is activated by phosphorylation and calcium ions 650 21.4 Glucagon and Epinephrine Signal the Need for Glycogen Breakdown 651 G proteins transmit the signal for the initiation of glycogen breakdown 651 Glycogen breakdown must be rapidly turned off when necessary 653 21.5 Glycogen Synthesis Requires Several Enzymes and Uridine Diphosphate Glucose 653 UDP-glucose is an activated form of glucose 653 Glycogen synthase catalyzes the transfer of glucose from UDP-glucose to growing chains 654 A branching enzyme forms a-1,6 linkages 655 Glycogen synthase is the key regulatory enzyme in glycogen synthesis 655 Glycogen is an efficient storage form of glucose 656 21.6 Glycogen Breakdown and Synthesis Are Reciprocally Controlled by Hormones 656 Protein phosphatase 1 reverses the effects of kinases on glycogen metabolism 656 Insulin stimulates glycogen synthesis by inactivating glycogen synthase kinase 658 Glycogen metabolism in the liver regulates the blood-glucose concentration 659 «№ Biochemists have uncovered the biochemical Ψ basis of multiple glycogen-storage diseases 660 CHAPTER
22 Fatty Acid and Triacylglycerol Metabolism 665 22.1 Triacylglycerols Are Highly Concentrated Energy Stores 666 Dietary lipids are digested by pancreatic lipases Dietary lipids are transported in chylomicrons 667 667 22.2 The Use of Fatty Acids as Fuel Requires Three stages of Processing 668 Mobilization: Triacylglycerols are hydrolyzed by hormone-stimulated lipases 668 Mobilization continues: Free fatty acids and glycerol are released into the blood 669 Activation: Fatty acids are linked to coenzyme A before they are oxidized 670 XVII Transport: Carnitine carries long-chain activated fatty acids into the mitochondrial matrix 671 Breakdown: Acetyl CoA, NADH, and FADH2 are generated in each round of fatty acid oxidation 672 The complete oxidation of palmitate yields 106 molecules of ATP 673 22.3 Unsaturated and Odd-Chain Fatty Acids Require Additional Steps for Degradation 674 An isomerase and a reductase are required for the oxidation of unsaturated fatty acids 674 Odd-chain fatty acids yield propionyl CoA in the final thiolysis step 675 Vitamin B12 contains a corrin ring and a cobalt atom 676 Mechanism: Methylmalonyl CoA mutase catalyzes a rearrangement to form succinyl CoA 677 SCIENTIST PROFILE Dorothy Hodgkin 677 Fatty acids are also oxidized in peroxisomes 678 Some fatty acids contribute to the development of pathological conditions 679 22.4 Ketone Bodies Are a Fuel Source Derived from Fats 679 Ketone bodies are a major fuel in some tissues 680 Diabetic ketoacidosis is a dangerous pathological ” condition caused by excessive ketone body formation 682 Animals cannot
convert fatty acids into glucose 683 22.5 Fatty Acids Are Synthesized by Fatty Acid Synthase 683 Fatty acid degradation and synthesis mirror each other in their chemical reactions 684 Fatty acids are synthesized and degraded by different pathways 685 The formation of malonyl CoA is the committed step in fatty acid synthesis 685 Intermediates in fatty acid synthesis are attached to an acyl carrier protein 685 Fatty acid synthesis consists of a series of condensation, reduction, dehydration, and reduction reactions 686 Fatty acids are synthesized by a multifunctional enzyme complex in animals 687 The synthesis of palmitate requires 8 molecules of acetyl CoA, 14 molecules of NADPH, and 7 molecules of ATP 690 Citrate carries acetyl groups from mitochondria to the cytoplasm for fatty acid synthesis 690 Several sources supply NADPH for fatty acid synthesis 691 Fatty acid metabolism is altered in tumor cells 691 Triacylglycerols may become an important renewable energy source 692 22.6 The Elongation and unsaturation of Fatty Acids Are Accomplished by Accessory Enzyme Systems 692 Membrane-bound enzymes generate unsaturated fatty acids 692 Eicosanoid hormones are derived from polyunsaturated fatty acids 693
xviii CONTENTS Pyruvate is an entry point into metabolism for a number of amino acids Oxaloacetate is an entry point into metabolism for aspartate and asparagine Alpha-ketoglutarate is an entry point into metabolism for amino acids with five-carbon chains Succinyl coenzyme A is a point of entry for several amino acids Methionine degradation requires the formation of a key methyl donor, S-adenosylmethionine Threonine deaminase initiates the degradation of threonine The branched-chain amino acids yield acetyl CoA, acetoacetate, or propionyl CoA Oxygenases are required for the degradation of aromatic amino acids Protein metabolism helps to power the flight of migratory birds 22.7 Acetyl CoA Carboxylase Plays a Key Role in 694 Controlling Fatty Acid Metabolism Acetyl CoA carboxylase is regulated by conditions in the cell 694 Acetyl CoA carboxylase is controlled by a variety of hormones 695 AMP-activated protein kinase is a key regulator of metabolism 696 CHAPTER 23 Protein Turnover and Amino Acid Catabolism 701 23.1 Proteins Are Degraded to Amino Acids 702 The digestion of dietary proteins begins in the stomach and is completed in the intestine Cellular proteins are degraded at different rates 702 703 23.2 Protein Turnover is Tightly Regulated 703 Ubiquitin tags proteins for destruction The proteasome digests the ubiquitin-tagged proteins The ubiquitin pathway and the proteasome have prokaryotic counterparts Protein degradation can be used to regulate biological function Ф236Inborn Errors of Metabolism Can • Disrupt Amino Acid Degradation 707 708 Alpha-amino groups are
converted into ammonium ions by the oxidative deamination of glutamate in the liver 708 SCIENTIST PROFILE Cecile Pickart 708 Mechanism: Pyridoxal phosphate forms Schiff-base intermediates in aminotransferases Aspartate aminotransferase is an archetypal pyridoxal-dependent transaminase •eg- Blood levels of aminotransferases serve a W diagnostic function Pyridoxal phosphate enzymes catalyze a wide array of reactions Serine and threonine can be directly deaminated Peripheral tissues transport nitrogen to the liver integration of Energy Metabolism 24.1 Caloric Homeostasis is a Means of Regulating Body weight 721 721 722 723 725 726 732 733 The brain plays a key role in caloric homeostasis 734 Short-term signals from the gastrointestinal tract induce feelings of satiety 735 Leptin and insulin regulate long-term control over caloric homeostasis 736 Leptin is one of several hormones secreted by adipose tissue 736 Leptin resistance may be a contributing factor to obesity 737 711 711 711 712 712 24.2 The Fasted-Fed Cycle is a Response to Eating and Sleeping Behaviors 738 713 The urea cycle begins with the formation of carbamoyl phosphate 714 Carbamoyl phosphate synthetase I is the key regulatory enzyme for urea synthesis 714 Carbamoyl phosphate reacts with ornithine to begin the urea cycle 715 The urea cycle is linked to gluconeogenesis 716 •eg. Inherited defects of the urea cycle cause 9 hyperammonemia and can lead to brain damage 717 Urea is not the only means of disposing of excess nitrogen 718 23.5 Carbon Atoms of Degraded Amino Acids Emerge as Major Metabolic Intermediates 721
CHAPTER 24 709 23.4 Ammonium ions Are Converted into Urea in Most Terrestrial Vertebrates 720 Branched-chain ketoaciduria is a serious disorder of branched-chain amino acid degradation 727 Phenylketonuria is one of the most common metabolic disorders Til 707 23.3 The First Step in Amino Acid Degradation Is the Removal of Nitrogen 719 example Determining Metabolic Products of Amino Acid Degradation 725 703 705 719 718 The postprandial state follows a meal 739 The postabsorptive state occurs at the beginning of a fast 739 The refed state occurs at the end of a long fast 741 24.3 Diabetes is a Common Metabolic • Disease Often Resulting from Obesity 741 Insulin initiates a complex signal-transduction pathway in muscle 742 Metabolic syndrome often precedes type 2 diabetes 743 Excess fatty acids in muscle modify metabolism 743 Insulin resistance in muscle facilitates pancreatic failure 744
CONTENTS Metabolie alterations in type 1 diabetes result from insulin insufficiency and glucagon excess 746 24.4 Exercise Beneficially Alters the Biochemistry of Cells 746 Fuel choice during exercise is determined by the intensity and duration of activity The perplexing symptoms of McArdle disease ™ result from the distinct ways skeletal muscle produces ATP Mitochondrial biogenesis is stimulated by muscular activity Exercise alters muscle and whole-body metabolism 746 749 749 750 Tetrahydrofolate carries activated one-carbon units at several oxidation levels 772 S-Adenosylmethionine is the major donor of methyl groups 774 Cysteine is synthesized from serine and homocysteine 776 High homocysteine levels correlate with vascular Ş disease 776 Shikimate and chorismate are intermediates in the biosynthesis of aromatic amino acids 776 Tryptophan synthase illustrates substrate channeling in enzymatic catalysis 779 25.3 Feedback inhibition Regulates Amino Acid EXAMPLE Measuring the impact of a Single Athletic Activity on Caloric Homeostasis 752 24.5 Starvation induces Protein Wasting and Ketone Body Formation xix 752 The first priority during starvation is the maintenance of blood-glucose concentration 752 Metabolic adaptations in prolonged starvation minimize protein degradation 753 24.6 Ethanol Alters Energy Metabolism in the Liver 755 Ethanol metabolism leads to an excess of NADH 755 Ethanol metabolites cause liver damage 755 Excess ethanol consumption disrupts vitamin metabolism 756 ■efe֊ Ethanol and defects in central energy metabolism ■ contribute to the development of cancer
758 Biosynthesis 780 Branched pathways require sophisticated regulation 780 The sensitivity of glutamine synthetase to allosteric regulation is altered by covalent modification 782 25.4 Amino Acids Are Precursors of Many Biomolecules 783 Glutathione, a gamma-glutamyl peptide, serves as a sulfhydryl buffer and an antioxidant 783 Nitric oxide, a short-lived signal molecule, is formed from arginine 784 Amino acids are precursors for a number of neurotransmitters 785 Porphyrins are synthesized from glycine and succinyl coenzyme A 786 efe. Porphyrins accumulate in some inherited W disorders of porphyrin metabolism 788 CHAPTER 25 Biosynthesis of Amino Acids 763 CHAPTER 26 Nucleotide Biosynthesis 25.1 Nitrogen Fixation: Microorganisms Use ATP and a Powerful Reductant to Reduce Atmospheric Nitrogen to Ammonia 764 Biological nitrogen fixation is catalyzed by the nitrogenase complex 764 The iron-molybdenum cofactor of nitrogenase binds and reduces atmospheric nitrogen 765 Ammonium ion is assimilated into an amino acid through glutamate and glutamine 766 25.2 Amino Acids Are Made from intermediates of the Citric Acid Cycle and Other Major Pathways 768 Human beings can synthesize some amino acids but must obtain others from their diet 768 Aspartate, alanine, and glutamate are formed by the addition of an amino group to an alpha-ketoacid 769 SCIENTIST PROFILE Beverly Guirard A common step determines the chirality of all amino acids The formation of asparagine from aspartate requires an adenylated intermediate Glutamate is the precursor of glutamine, proline, and arginine
3-Phosphoglycerate is the precursor of serine, cysteine, and glycine 770 770 770 771 772 791 26.1 Nucleotides Can Be Synthesized by de Novo or Salvage Pathways 792 26.2 The Pyrimidine Ring is Assembled from CO2, Ammonia, and Aspartate 793 Bicarbonate and other oxygenated carbon compounds are activated by phosphorylation 793 The side chain of glutamine can be hydrolyzed to generate ammonia 794 The pyrimidine ring is completed and coupled to ribose 794 Nucleotide mono-, di-, and triphosphates are interconvertible 796 CTP is formed by amination of UTP 796 Salvage pathways recycle pyrimidine bases 796 26.3 Purine Bases Can Be Synthesized from Glycine, Aspartate, and Other Components 797 The purine ring system is assembled on ribose phosphate 797 The purine ring is assembled by successive steps of activation by phosphorylation followed by displacement 797 AMP and GMP are formed from IMP 799
XX CONTENTS Enzymes of the purine biosynthesis pathway associate with one another 800 Salvage pathways economize intracellular resource consumption 800 An alternative to adenine is used by some viruses 801 26.4 Deoxyribonucleotides Are Synthesized by the Reduction of Ribonucleotides 801 Ribonucleotide reduction occurs via a radical mechanism Stable radicals are present in ribonucleotide reductases SCIENTIST PROFILE JoAnne Stubbe Thymidylate is formed by the methylation of deoxyuridylate Several valuable anticancer drugs block the ™ synthesis of thymidylate 802 803 804 804 805 26.5 Key Steps in Nucleotide Biosynthesis Are Regulated by Feedback Inhibition 807 Pyrimidine biosynthesis is regulated by aspartate transcarbamoylase The synthesis of purine nucleotides is controlled by feedback inhibition at several sites The synthesis of deoxyribonucleotides is controlled by the regulation of ribonucleotide reductase 807 807 808 26.6 Disruptions in Nucleotide Metabolism Can Cause Pathological Conditions 809 The loss of adenosine deaminase activity results in severe combined immunodeficiency 809 Gout is induced by high serum levels of urate 810 Lesch-Nyhan syndrome is a dramatic consequence of mutations in a salvage-pathway enzyme 810 CHAPTER 27 Biosynthesis of Membrane Lipids and Steroids 814 27.1 Phosphatidate is a Common intermediate in the Synthesis of Phospholipids and Triacylglycerols 815 The synthesis of phospholipids requires an activated intermediate 816 Some phospholipids are synthesized from an activated alcohol 817 Phosphatidylcholine is an abundant phospholipid 818 Base-
exchange reactions can generate phospholipids 818 Sphingolipids are synthesized from ceramide 819 Tay-Sachs disease results from the disruption ™ of lipid metabolism 820 Phosphatidic acid phosphatase is a key regulatory enzyme in lipid metabolism 821 27.2 Cholesterol is Synthesized from Acetyl Coenzyme A in Three Stages Stage 1: The synthesis of mevalonate initiates the synthesis of cholesterol Stage 2: Squalene (C30) is synthesized from six molecules of isopentenyl pyrophosphate (C5) Stage 3: Squalene cyclizes to form cholesterol 821 822 823 824 27.3 The Regulation of Cholesterol Biosynthesis Takes Place at Several Levels 825 Lipoproteins transport cholesterol and triacylglycerols throughout the organism 827 Low-density lipoproteins play a central role in cholesterol metabolism 829 fe The absence of the LDL receptor leads to ” hypercholesterolemia and atherosclerosis 830 Mutations in the LDL receptor prevent LDL release and result in receptor destruction 831 Cycling of the LDL receptor is regulated 832 HDL appears to protect against atherosclerosis 832 ^fe The clinical management of cholesterol levels Ж can be understood at the biochemical level 832 t 27.4 Important Biochemicals Are Synthesized from Cholesterol and isoprene 833 Steroids are hydroxylated by cytochrome P450 monooxygenases that use NADPH and O2 834 fe Cytochrome P450s are widespread and perform W many functions 836 SCIENTIST PROFILE Namandjé Bumpus 836 Pregnenolone is a precursor of many other steroids 836 Vitamin D is derived from cholesterol by the ring-splitting activity of light 839 Five-carbon units are
joined to form a wide variety of biomolecules 840 Some isoprenoids have industrial applications 841 CHAPTER 28 Replication, Repair, and Recombination dna 845 28.1 DNA Replication Proceeds by the Polymerization of Deoxyribonucleoside Triphosphates Along a Template 846 DNA polymerases require a template and a primer 846 DNA polymerases have common structural features 846 Bound metal ions participate in the polymerase reaction 847 The specificity of replication is dictated by complementarity of shape between bases 847 An RNA primer enables DNA synthesis to begin 848 SCIENTIST PROFILE Tsuneko and Reiji Okazaki 849 One strand of DNA is made continuously, whereas the other strand is synthesized in fragments 849 DNA ligase seals breaks in double-stranded DNA 849 The separation of DNA strands requires specific helicases and ATP hydrolysis 850 28.2 DNA Unwinding and Supercoiling Are Controlled by Topoisomerases 851 The linking number, a topological property, determines the degree of supercoiling 853 Topoisomerases prepare the double helix for unwinding 853 Type I topoisomerases relax supercoiled structures 854 Туре II topoisomerases introduce negative supercoils through coupling to ATP hydrolysis 855
CONTENTS 28.3 DNA Replication IS Highly Coordinated 857 DNA replication requires highly processive polymerases 857 The leading and lagging strands are synthesized in a coordinated fashion 858 DNA replication in E. coli begins at a unique site 860 DNA replication in eukaryotes is initiated at multiple sites 861 The eukaryotic cell cycle ensures coordination of DNA replication and cell division 862 Telomeres are protective structures at the ends of linear chromosomes 863 Telomeres are replicated by telomerase, a specialized polymerase that carries its own RNA template 863 28.4 Many Types of DNA Damage Can Be Repaired 864 Errors can arise in DNA replication 864 DNA can be damaged by oxidizing agents, alkylating agents, and light 865 DNA damage can be detected and repaired by a variety of systems 866 The presence of thymine instead of uracil in DNA permits the repair of deaminated cytosine 868 tSome genetic diseases are caused by the expansion of repeats of three nucleotides 869 Many cancers are initiated by the defective repair of DNA 869 Many potential carcinogens can be detected by their mutagenic action on bacteria 871 28.5 DNA Recombination Plays Important Roles in Replication, Repair, and Other Processes 872 RecA can initiate recombination by promoting strand invasion 872 Some recombination reactions proceed through Holliday-junction intermediates 873 CHAPTER 29 Functions, Biosynthesis, and Processing rna 879 29.1 RNA Molecules Play Different Roles, Primarily in Gene Expression 880 RNAs play key roles in protein biosynthesis 880 Some RNAs can guide modifications of
themselves or other RNAs 880 Some viruses have RNA genomes 880 Messenger RNA vaccines provide protection ” against diseases 880 29.2 RNA Polymerases Catalyze Transcription RNA synthesis comprises three stages: initiation, elongation, and termination RNA polymerases catalyze the formation of a phosphodiester bond RNA chains are formed de novo and grow in the 5'-to-3' direction RNA polymerases backtrack and correct errors 881 882 882 884 885 RNA polymerase binds to promoter sites on the DNA template in bacteria to initiate transcription Sigma subunits of RNA polymerase in bacteria recognize promoter sites The template double helix must be unwound for transcription to take place Elongation takes place at transcription bubbles that move along the DNA template Sequences within the newly transcribed RNA signal termination In bacteria, the rho protein helps to terminate the transcription of some genes 29.3 Transcription Is Highly Regulated Alternative sigma subunits in bacteria control transcription in response to changes in conditions Some messenger RNAs directly sense metabolite concentrations Control of transcription in eukaryotes is highly complex Eukaryotic DNA is organized into chromatin Three types of RNA polymerase synthesize RNA in eukaryotic cells Three common elements can be found in the RNA polymerase II promoter region Regulatory cis-acting elements are recognized by different mechanisms The TFIID protein complex initiates the assembly of the active transcription complex in eukaryotes Enhancer sequences can stimulate transcription at start sites thousands of bases
away xxi 886 886 887 888 888 889 890 890 891 892 893 894 896 896 896 898 29.4 Some RNA Transcription Products Are Processed 898 Precursors of transfer and ribosomal RNA are cleaved and chemically modified after transcription 898 899 RNA polymerase I produces three ribosomal RNAs RNA polymerase III produces transfer RNAs 900 The product of RNA polymerase II, the pre-mRNA 900 transcript, acquires a 5' cap and a 3' poly(A) tail Sequences at the ends of introns specify splice sites in mRNA precursors 901 Splicing consists of two sequential transesterification 902 reactions Small nuclear RNAs in spliceosomes catalyze the 903 splicing of mRNA precursors Mutations that affect pre-mRNA splicing cause ™ disease 906 Most human pre-mRNAs can be spliced in alternative 906 ways to yield different proteins Transcription and mRNA processing are coupled 908 Small regulatory RNAs are cleaved from larger 908 precursors 908 RNA editing can lead to specific changes in mRNA 29.5 The Discovery of Catalytic RNA Revealed 909 a Unique Splicing Mechanism Some RNAs can promote their own splicing 909 RNA enzymes can promote many reactions, including RNA polymerization 912 912 SCIENTIST PROFILE Thomas Cech
ХХІІ CONTENTS 30.4 Ribosomes Bound to the Endoplasmic Reticulum Manufacture Secretory and CHAPTER ЗО Protein Biosynthesis 30.1 Protein Biosynthesis Requires the Translation of Nucleotide Sequences into Amino Acid Sequences The biosynthesis of long proteins requires a low error frequency Transfer RNA (tRNA) molecules have a common design Some transfer RNA molecules recognize more than one codon because of wobble in base-pairing 30.2 Aminoacyl-tRNA Synthetases Establish the Genetic Code Amino acids are first activated by adenylation Aminoacyl-tRNA synthetases have highly discriminating amino acid activation sites Proofreading by aminoacyl-tRNA synthetases increases the fidelity of protein biosynthesis Kinetic proofreading increases the fidelity of protein biosynthesis Synthetases recognize various features of transfer RNA molecules Aminoacyl-tRNA synthetases are divided into two classes 916 Membrane Proteins 917 917 918 Ribosomal RNAs (5Տ, 16Տ, and 23S rRNA) play central roles in protein biosynthesis Ribosomes have three transfer RNA-binding sites that bridge the 30Տ and 50Տ subunits The start signal is usually AUG preceded by several bases that pair with 16S rRNA Bacterial protein biosynthesis is initiated by N-formylmethionyl-transfer RNA N-Formylmethionyl-tRNAWet is placed in the P site of the ribosome in the formation of the 70S initiation complex Elongation factors deliver aminoacyl-tRNAs to the ribosome Peptidyl transferase catalyzes peptide-bond formation GTP hydrolysis-driven translocation of tRNAs and mRNA follows peptide-bond formation In bacteria, transcription and
translation are coupled in space and time Protein biosynthesis is terminated by release factors that read stop codons Eukaryotic protein biosynthesis differs from bacterial protein biosynthesis primarily in translation initiation Ribosomes selectively control gene expression Scientists have manipulated protein biosynthesis pathways to incorporate unnatural amino acids in preselected positions SCIENTIST PROFILE Ada Yonath 30.5 A Variety of Antibiotics and Toxins Inhibit Protein Biosynthesis Some antibiotics inhibit protein biosynthesis •Qj- Diphtheria toxin blocks protein biosynthesis ■ in eukaryotes by inhibiting translocation Some toxins modify 28S ribosomal RNA 920 921 921 Control of Gene Expression Specific Regulatory Sites 924 * 926 926 927 928 929 930 931 931 932 933 935 935 936 938 938 938 939 940 941 942 942 943 944 949 31.1 Bacterial DNA-Binding Proteins Bind to 923 925 939 CHAPTER 31 922 30.3 The Ribosome is the Site of Protein Biosynthesis Protein biosynthesis begins on ribosomes that are free in the cytoplasm Signal sequences mark proteins for translocation across the endoplasmic reticulum membrane Transport vesicles carry cargo proteins to their final destinations Many DNA-binding proteins match the symmetry in their target DNA sequences The helix-turn-helix motif is common to many bacterial DNA-binding proteins 950 950 951 31.2 In Bacteria, Genes Are Often Arranged into Clusters Under the Control of a Single Regulatory Sequence An operon consists of regulatory elements and protein-encoding genes The lac repressor protein can block transcription Ligand binding
can induce structural changes in regulatory proteins The operon is a common regulatory unit in bacteria Some DNA-binding proteins stimulate transcription 951 952 953 954 955 955 31.3 Regulatory circuits Can Result in Switching Between Patterns of Gene Expression The λ repressor regulates its own expression A circuit based on the λ repressor and Cro forms a genetic switch 31.4 Regulation of Gene Expression Is More Complex in Eukaryotes A range of DNA-binding motifs are employed by eukaryotic DNA-binding proteins Activation domains interact with other proteins Multiple transcription factors interact with eukaryotic regulatory regions 956 957 957 958 958 960 960 31.5 The Control of Gene Expression in Eukaryotes 961 Can Require Chromatin Remodeling Chromatin remodeling and DNA methylation regulate access to DNA-binding sites Epigenetic modifications influence gene expression SCIENTIST PROFILE Sarah Stewart 961 962 962
CONTENTS Enhancers stimulate transcription by recruiting activator proteins that alter chromatin structure 962 Nuclear hormone receptors are transcription factors that cause changes in chromatin structure 963 Nuclear hormone receptors regulate transcription by recruiting coactivators to the transcription complex 965 Chromatin structure is modulated through covalent modifications of histone tails 965 Transcriptional repression can be achieved through histone deacetylation and other modifications 967 High-throughput screening expands the opportunity for lead identification Screening libraries can be prepared using combinatorial chemistry DNA-encoded libraries provide very large compound libraries for lead identification Phenotypic screening provides an alternative to the target-centered approach 32.3 compounds Must Meet stringent Criteria to Be Developed into Drugs Drugs must be potent and selective 31.6 Gene Expression Can Be Controlled at the Posttranscriptional Level 967 EXAMPLE Determining the ICM for an inhibitor Attenuation regulates transcription in bacteria through the modulation of nascent RNA secondary structure 967 Eukaryotes use different mechanisms to control gene expression at the posttranscriptional level 969 Genes associated with iron metabolism are translationally regulated in animals 970 Small RNAs are involved in posttranscriptional gene regulation in eukaryotes 971 CHAPTER 32 977 978 978 Drug targets must be validated and tractable Serendipitous observations can drive drug development 32.2 Lead Molecules Can Be Discovered in Many Ways Natural products are
a valuable source of lead molecules 32.4 Biologies Are a Growing Family of Drugs The majority of biologies are recombinant proteins Monoclonal antibodies are highly specific and potent recombinant protein biologies SCIENTIST PROFILE Gertrude Elion Principles of Drug Discovery and Development 32.1 Drug Discovery Begins with Target Identification and Validation Drugs must have suitable properties to reach their targets Toxicity can limit drug effectiveness Lead molecules can be optimized on the basis of three-dimensional structural information about their targets 32.5 The Clinical Development of Medicines Proceeds Through Several Phases Clinical trials are time-consuming and expensive The evolution of drug resistance can limit the utility of drugs for infectious agents and cancer xxiii 981 982 984 985 986 986 987 988 992 993 995 995 995 996 996 996 998 979 CHEMISTRY REVIEW APPENDIX ANSWERS TO SELF-CHECK QUESTIONS 980 ANSWERS TO PROBLEMS 980 INDEX Al A5 A11 11 |
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| author | Berg, Jeremy M. 1958- Gatto, Gregory J. Jr Hines, Justin Heller, Jutta Beneken Tymoczko, John L. 1948-2019 Stryer, Lubert 1938-2024 |
| author_GND | (DE-588)12460109X (DE-588)1090925050 (DE-588)1293683906 (DE-588)1303576791 (DE-588)124601103 (DE-588)124601197 |
| author_facet | Berg, Jeremy M. 1958- Gatto, Gregory J. Jr Hines, Justin Heller, Jutta Beneken Tymoczko, John L. 1948-2019 Stryer, Lubert 1938-2024 |
| author_role | aut aut aut aut aut aut |
| author_sort | Berg, Jeremy M. 1958- |
| author_variant | j m b jm jmb g j g gj gjg j h jh j b h jb jbh j l t jl jlt l s ls |
| building | Verbundindex |
| bvnumber | BV048891788 |
| classification_rvk | WD 4010 WD 4000 |
| classification_tum | CHE 800 |
| ctrlnum | (OCoLC)1379404324 (DE-599)BVBBV048891788 |
| dewey-full | 572 |
| dewey-hundreds | 500 - Natural sciences and mathematics |
| dewey-ones | 572 - Biochemistry |
| dewey-raw | 572 |
| dewey-search | 572 |
| dewey-sort | 3572 |
| dewey-tens | 570 - Biology |
| discipline | Chemie / Pharmazie Biologie |
| edition | Tenth edition |
| format | Book |
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| genre_facet | Lehrbuch |
| id | DE-604.BV048891788 |
| illustrated | Illustrated |
| indexdate | 2025-02-11T11:01:35Z |
| institution | BVB |
| isbn | 9781319498504 9781319333621 9781319498405 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-034156360 |
| oclc_num | 1379404324 |
| open_access_boolean | |
| owner | DE-91G DE-BY-TUM DE-355 DE-BY-UBR DE-91S DE-BY-TUM DE-M49 DE-BY-TUM DE-578 DE-20 DE-19 DE-BY-UBM DE-11 DE-1102 DE-703 DE-83 DE-384 |
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| physical | xxxvii, 1001, A31, I44 Seiten Illustrationen, Diagramme |
| publishDate | 2023 |
| publishDateSearch | 2023 |
| publishDateSort | 2023 |
| publisher | Macmillan Learning |
| record_format | marc |
| spellingShingle | Berg, Jeremy M. 1958- Gatto, Gregory J. Jr Hines, Justin Heller, Jutta Beneken Tymoczko, John L. 1948-2019 Stryer, Lubert 1938-2024 Biochemistry Physiologische Chemie (DE-588)4076124-1 gnd Biochemie (DE-588)4006777-4 gnd |
| subject_GND | (DE-588)4076124-1 (DE-588)4006777-4 (DE-588)4123623-3 |
| title | Biochemistry |
| title_auth | Biochemistry |
| title_exact_search | Biochemistry |
| title_full | Biochemistry Jeremy M. Berg, Gregory J. Gatto, Jr., Justin K. Hines, Jutta Beneken Heller, John L. Tymoczko, Lubert Stryer |
| title_fullStr | Biochemistry Jeremy M. Berg, Gregory J. Gatto, Jr., Justin K. Hines, Jutta Beneken Heller, John L. Tymoczko, Lubert Stryer |
| title_full_unstemmed | Biochemistry Jeremy M. Berg, Gregory J. Gatto, Jr., Justin K. Hines, Jutta Beneken Heller, John L. Tymoczko, Lubert Stryer |
| title_short | Biochemistry |
| title_sort | biochemistry |
| topic | Physiologische Chemie (DE-588)4076124-1 gnd Biochemie (DE-588)4006777-4 gnd |
| topic_facet | Physiologische Chemie Biochemie Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=034156360&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT bergjeremym biochemistry AT gattogregoryj biochemistry AT hinesjustin biochemistry AT hellerjuttabeneken biochemistry AT tymoczkojohnl biochemistry AT stryerlubert biochemistry |
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