Biochemistry: the molecular basis of cell structure and function
Gespeichert in:
| 1. Verfasser: | |
|---|---|
| Format: | Buch |
| Sprache: | English |
| Veröffentlicht: |
New York
Worth
1976
|
| Ausgabe: | 2. ed., 2. print. |
| Schlagworte: | |
| Online-Zugang: | Inhaltsverzeichnis |
| Beschreibung: | XXIII, 1104 S. Ill., graph. Darst. |
| ISBN: | 0879010479 |
Internformat
MARC
| LEADER | 00000nam a2200000 c 4500 | ||
|---|---|---|---|
| 001 | BV008070512 | ||
| 003 | DE-604 | ||
| 005 | 20141205 | ||
| 007 | t | ||
| 008 | 930712s1976 ad|| |||| 00||| eng d | ||
| 020 | |a 0879010479 |9 0-87901-047-9 | ||
| 035 | |a (OCoLC)254156782 | ||
| 035 | |a (DE-599)BVBBV008070512 | ||
| 040 | |a DE-604 |b ger |e rakwb | ||
| 041 | 0 | |a eng | |
| 049 | |a DE-19 |a DE-188 | ||
| 084 | |a WD 4000 |0 (DE-625)148175: |2 rvk | ||
| 084 | |a WD 4010 |0 (DE-625)148176: |2 rvk | ||
| 100 | 1 | |a Lehninger, Albert L. |d 1917-1986 |e Verfasser |0 (DE-588)132539519 |4 aut | |
| 245 | 1 | 0 | |a Biochemistry |b the molecular basis of cell structure and function |c Albert L. Lehninger |
| 250 | |a 2. ed., 2. print. | ||
| 264 | 1 | |a New York |b Worth |c 1976 | |
| 300 | |a XXIII, 1104 S. |b Ill., graph. Darst. | ||
| 336 | |b txt |2 rdacontent | ||
| 337 | |b n |2 rdamedia | ||
| 338 | |b nc |2 rdacarrier | ||
| 650 | 0 | 7 | |a Zelle |0 (DE-588)4067537-3 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Biochemie |0 (DE-588)4006777-4 |2 gnd |9 rswk-swf |
| 650 | 0 | 7 | |a Funktion |0 (DE-588)4195664-3 |2 gnd |9 rswk-swf |
| 655 | 7 | |8 1\p |0 (DE-588)4123623-3 |a Lehrbuch |2 gnd-content | |
| 689 | 0 | 0 | |a Zelle |0 (DE-588)4067537-3 |D s |
| 689 | 0 | 1 | |a Funktion |0 (DE-588)4195664-3 |D s |
| 689 | 0 | |8 2\p |5 DE-604 | |
| 689 | 1 | 0 | |a Biochemie |0 (DE-588)4006777-4 |D s |
| 689 | 1 | |8 3\p |5 DE-604 | |
| 856 | 4 | 2 | |m SWB Datenaustausch |q application/pdf |u http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005311927&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |3 Inhaltsverzeichnis |
| 999 | |a oai:aleph.bib-bvb.de:BVB01-005311927 | ||
| 883 | 1 | |8 1\p |a cgwrk |d 20201028 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | |
| 883 | 1 | |8 2\p |a cgwrk |d 20201028 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | |
| 883 | 1 | |8 3\p |a cgwrk |d 20201028 |q DE-101 |u https://d-nb.info/provenance/plan#cgwrk | |
Datensatz im Suchindex
| _version_ | 1804122437736988672 |
|---|---|
| adam_text | IMAGE 1
IX
CONTENTS
HOW DO WE UNDERSTAND LIFE? 1
PART I: BIOLOGICAL MOLECULES 4
CHAPTER 1 FROM GENES TO RNA AND PROTEINS 5
CHAPTER 2 NUCLEIC ACID STRUCTURE 51
CHAPTER 3 GLYCANS AND LIPIDS 91
CHAPTER 4 PROTEIN STRUCTURE 131
CHAPTER 5 EVOLUTIONARY VARIATION IN PROTEINS 191
PART II: ENERGY AND ENTROPY 238
CHAPTER 6 ENERGY AND INTERMOLECULAR FORCES 239
CHAPTER 7 ENTROPY 293
CHAPTER 8 LINKING ENERGY AND ENTROPY: THE BOLTZMANN DISTRIBUTION 341
PART III: FREE ENERGY 382
CHAPTER 9 FREE ENERGY 383
CHAPTER 10 CHEMICAL POTENTIAL AND THE DRIVE TO EQUILIBRIUM 413 CHAPTER
11 VOLTAGES AND FREE ENERGY 459
PART IV: MOLECULAR INTERACTIONS 530
CHAPTER 12 MOLECULAR RECOGNITION: THE THERMODYNAMICS OF BINDING 531
CHAPTER 13 SPECIFICITY OF MACROMOLECULAR RECOGNITION 581 CHAPTER 14
ALLOSTERY 633
PART V: KINETICS AND CATALYSIS 672
CHAPTER 15 THE RATES OF MOLECULAR PROCESSES 673 CHAPTER 16 PRINCIPLES OF
ENZYME CATALYSIS 721
CHAPTER 17 DIFFUSION AND TRANSPORT 787
PART VI: ASSEMBLY AND ACTIVITIY 838
CHAPTER 18 FOLDING 839
CHAPTER 19 FIDELITY IN DNA AND PROTEIN SYNTHESIS 887
GLOSSARY 939
INDEX 965
IMAGE 2
DETAILED CONTENTS
HOW DO WE UNDERSTAND LIFE? 1
PART I: BIOLOGICAL MOLECULES 4
CHAPTER 1 FROM GENES TO RNA AND PROTEINS 5 A. INTERACTIONS BETWEEN
MOLECULES 6 1.1 THE ENERGY OF INTERACTION BETWEEN TWO MOLECULES IS
DETERMINED BY NONCOVALENT INTERACTIONS 6
1.2 NEUTRAL ATOMS ATTRACT AND REPEL EACH OTHER AT CLOSE DISTANCES
THROUGH VAN DER WAALS INTERACTIONS 8
1.3 IONIC INTERACTIONS BETWEEN CHARGED ATOMS CAN BE VERY STRONG, BUT ARE
ATTENUATED BY WATER 10 1.4 HYDROGEN BONDS ARE VERY COMMON IN BIOLOGICAL
MACROMOLECULES 12
B. INTRODUCTION TO NUCLEIC ACIDS AND PROTEINS 15
1.5 NUCLEOTIDES HAVE PENTOSE SUGARS ATTACHED TO NITROGENOUS BASES AND
PHOSPHATE GROUPS 15 1.6 THE NUCLEOTIDE BASES IN RNA AND DNA ARE
SUBSTITUTED PYRIMIDINES OR PURINES 18
1.7 DNA AND RNA ARE FORMED BY SEQUENTIAL REACTIONS THAT UTILIZE
NUCLEOTIDE TRIPHOSPHATES 20 1.8 DNA FORMS A DOUBLE HELIX WITH
ANTIPARALLEL STRANDS 22
1.9 THE DOUBLE HELIX IS STABILIZED BY THE STACKING OF BASE PAIRS 24
1.10 PROTEINS ARE POLYMERS OF AMINO ACIDS 25
1.11 PROTEINS ARE FORMED BY CONNECTING AMINO ACIDS BY PEPTIDE BONDS 25
1.12 AMINO ACIDS ARE CLASSIFIED BASED ON THE PROPERTIES OF THEIR
SIDECHAINS 29
1.13 PROTEINS APPEAR IRREGULAR IN SHAPE 30
1.14 PROTEIN CHAINS FOLD UP TO FORM HYDROPHOBIC CORES 31
1.15 A HELICES AND P SHEETS ARE THE ARCHITECTURAL ELEMENTS OF PROTEIN
STRUCTURE 31
C. REPLICATION, TRANSCRIPTION, AND TRANSLATION 35
1.16 DNA REPLICATION IS A COMPLEX PROCESS INVOLVING MANY PROTEIN
MACHINES 35
1.17 TRANSCRIPTION GENERATES RNAS WHOSE SEQUENCES ARE DICTATED BY THE
SEQUENCE OF NUCLEOTIDES IN GENES 38
1.18 SPLICING OF RNA IN EUKARYOTIC CELLS CAN GENERATE A DIVERSITY OF
RNAS FROM A SINGLE GENE 1.19 THE GENETIC CODE RELATES TRIPLETS OF
NUCLEOTIDES IN A GENE SEQUENCE TO EACH AMINO ACID IN A
PROTEIN SEQUENCE 1.20 TRANSFER RNAS WORK WITH THE RIBOSOME TO TRANSLATE
MRNA SEQUENCES INTO PROTEINS 1.21 THE MECHANISM FOR THE TRANSFER OF
GENETIC
INFORMATION IS HIGHLY CONSERVED 1.22 THE DISCOVERY OF RETROVIRUSES
SHOWED THAT INFORMATION STORED IN RNA CAN BE TRANSFERRED TO DNA SUMMARY
KEY CONCEPTS
PROBLEMS FURTHER READING
CHAPTER 2 NUCLEIC ACID STRUCTURE
39
39
42
43
44 46 47 48
50
51
52
52
A. DOUBLE-HELICAL STRUCTURES OF RNA AND DNA 2.1 THE DOUBLE HELIX IS THE
PRINCIPAL SECONDARY STRUCTURE OF DNA AND RNA 2.2 HYDROGEN BONDING
BETWEEN BASES IS IMPORTANT
FOR THE FORMATION OF DOUBLE HELICES, BUT ITS EFFECT IS WEAKENED DUE TO
INTERACTIONS WITH WATER 53 2.3 THE ELECTRONIC POLARIZATION OF THE BASES
CONTRIBUTES TO STRONG STACKING INTERACTIONS
BETWEEN BASES 54
2.4 METAL IONS HELP SHIELD ELECTROSTATIC REPULSIONS BETWEEN THE
PHOSPHATE GROUPS 55
2.5 THERE ARE TWO COMMON RELATIVE ORIENTATIONS OF THE BASE AND THE SUGAR
56
2.6 THE RIBOSE RING HAS ALTERNATE CONFORMATIONS DEFINED BY THE SUGAR
PUCKER 56
2.7 RNA CANNOT ADOPT THE STANDARD WATSON-CRICK DOUBLE-HELICAL STRUCTURE
BECAUSE OF CONSTRAINTS ON ITS SUGAR PUCKER 58
2.8 THE STANDARD WATSON-CRICK MODEL OF DOUBLE-HELICAL DNA IS THE B-FORM
59
2.9 B-FORM DNA ALLOWS SEQUENCE-SPECIFIC RECOGNITION OF THE MAJOR GROOVE,
WHICH HAS A GREATER INFORMATION CONTENT THAN THE MINOR GROOVE 60
2.10 RNA ADOPTS THE A-FORM DOUBLE-HELICAL CONFORMATION 61
2.11 THE MAJOR GROOVE OF A-FORM DOUBLE HELICES IS LESS ACCESSIBLE TO
PROTEINS THAN THAT OF B-FORM DNA 62
IMAGE 3
DETAILED CONTENTS XI
2.12 Z-FORM DNA IS A LEFT-HANDED DOUBLE-HELICAL STRUCTURE 62
2.13 THE DNA DOUBLE HELIX IS QUITE DEFORMABLE 65 2.14 DNA SUPERCOILING
CAN OCCUR WHEN THE ENDS OF DOUBLE HELICES ARE CONSTRAINED 67
2.15 WRITHE, LINKING NUMBER, AND TWIST ARE MATHEMATICAL PARAMETERS THAT
DESCRIBE THE SUPERCOILING OF DNA 69
2.16 THE WRITHE, TWIST, AND LINKING NUMBER ARE RELATED TO EACH OTHER IN
A SIMPLE WAY 70
2.17 THE DNA IN CELLS IS SUPERCOILED 71
2.18 LOCAL CONFORMATIONAL CHANGES IN THE DNA ALSO AFFECT SUPERCOILING 72
B. THE FUNCTIONAL VERSATILITY OF RNA 73 2.19 WOBBLE BASE PAIRS ARE OFTEN
SEEN IN RNA 73 2.20 NONSTANDARD BASE-PAIRING IS COMMON IN RNA 75 2.21
SOME RNA MOLECULES CONTAIN MODIFIED
NUCLEOTIDES 76
2.22 A TETRALOOP IS A COMMON SECONDARY STRUCTURAL MOTIF THAT CAPS RNA
HAIRPINS 79
2.23 INTERACTIONS WITH METAL IONS HELP RNAS TO FOLD 80 2.24 RNA TERTIARY
STRUCTURE INVOLVES INTERACTIONS BETWEEN SECONDARY STRUCTURAL ELEMENTS 81
2.25 HELICES IN RNA OFTEN INTERACT THROUGH COAXIAL
BASE STACKING OR THE FORMATION OF PSEUDOKNOTS 82 2.26 VARIOUS
INTERACTIONS BETWEEN NUCLEOTIDES STABILIZE RNA TERTIARY STRUCTURE 84
SUMMARY 86
KEY CONCEPTS 87
PROBLEMS 88
FURTHER READING 90
CHAPTER 3 GLYCANS AND LIPIDS 91
A. GLYCANS 91
3.1 SIMPLE SUGARS ARE COMPRISED PRIMARILY OF HYDROXYLATED CARBONS 91
3.2 MANY CYCLIC SUGAR MOLECULES CAN EXIST IN ALTERNATIVE ANOMERIC FORMS
92
3.3 SUGAR RINGS OFTEN HAVE MANY LOW ENERGY CONFORMATIONS 94
3.4 MANY SUGARS ARE STRUCTURAL ISOMERS OF IDENTICAL COMPOSITION, BUT
WITH DIFFERENT STEREOCHEMISTRY 95 3.5 SOME SUGARS HAVE OTHER CHEMICAL
FUNCTIONALITIES IN ADDITION TO ALCOHOL GROUPS 97
3.6 GLYCANS FORM POLYMERIC STRUCTURES THAT CAN HAVE BRANCHED LINKAGES 98
3.7 DIFFERENCES IN ANOMERIC LINKAGES LEAD TO DRAMATIC DIFFERENCES IN
POLYMERIC FORMS OF GLUCOSE 99 3.8 ACETYLATION OR OTHER CHEMICAL
MODIFICATION LEADS TO DIVERSITY IN SUGAR POLYMER PROPERTIES 101 3.9
GLYCANS MAY BE ATTACHED TO PROTEINS OR LIPIDS 102 3.10 THE DECORATION OF
PROTEINS WITH GLYCANS IS NOT
TEMPLATED 104
3.11 GLYCAN MODIFICATIONS ALTER THE PROPERTIES OF PROTEINS 105
3.12 PROTEIN-GLYCAN INTERACTIONS ARE IMPORTANT IN CELLULAR RECOGNITION
106
B. LIPIDS AND MEMBRANES 108
3.13 THE MOST ABUNDANT LIPIDS ARE GLYCEROPHOSPHOLIPIDS 109
3.14 OTHER CLASSES OF LIPIDS HAVE DIFFERENT MOLECULAR FRAMEWORKS 110
3.15 LIPIDS FORM ORGANIZED STRUCTURES SPONTANEOUSLY 113 3.16 THE SHAPES
OF LIPID MOLECULES AFFECT THE STRUCTURES THEY FORM 113
3.17 DETERGENTS ARE AMPHIPHILIC MOLECULES THAT TEND TO FORM MICELLES
RATHER THAN BILAYERS 115
3.18 LIPIDS IN BILAYERS MOVE FREELY IN TWO DIMENSIONS 116 3.19 LIPID
COMPOSITION AFFECTS THE PHYSICAL PROPERTIES OF MEMBRANES 118
3.20 PROTEINS CAN BE ASSOCIATED WITH MEMBRANES BY ATTACHMENT TO LIPID
ANCHORS 121
3.21 LIPID MOLECULES CAN BE SEQUESTERED AND TRANSPORTED BY PROTEINS 122
3.22 DIFFERENT KINDS OF CELLS AND ORGANELLES HAVE DIFFERENT MEMBRANE
COMPOSITIONS 123
3.23 CELL WALLS ARE REINFORCED MEMBRANES 125
SUMMARY 126
KEY CONCEPTS 127
PROBLEMS 128
FURTHER READING 129
CHAPTER 4 PROTEIN STRUCTURE 131
131 A. GENERAL PRINCIPLES 4.1 PROTEIN STRUCTURES DISPLAY A HIERARCHICAL
ORGANIZATION 131
4.2 PROTEIN DOMAINS ARE THE FUNDAMENTAL UNITS OF TERTIARY STRUCTURE 133
4.3 PROTEIN FOLDING IS DRIVEN BY THE FORMATION OF A HYDROPHOBIC CORE 134
4.4 THE FORMATION OF A HELICES AND P SHEETS SATISFIES THE
HYDROGEN-BONDING REQUIREMENTS OF THE PROTEIN BACKBONE 136
B. BACKBONE CONFORMATION 137
4.5 PROTEIN FOLDING INVOLVES CONFORMATIONAL CHANGES IN THE PEPTIDE
BACKBONE 137
4.6 AMINO ACIDS ARE CHIRAL AND ONLY THE L FORM STEREOISOMER IS FOUND IN
GENETICALLY ENCODED PROTEINS 138
4.7 THE PEPTIDE BOND HAS PARTIAL DOUBLE BOND CHARACTER, SO ROTATIONS
ABOUT IT ARE HINDERED 139 4.8 PEPTIDE GROUPS CAN BE IN CIS OR TRANS
CONFORMATIONS 140
4.9 THE BACKBONE TORSION ANGLES § (PHI) AND Y (PSI) DETERMINE THE
CONFORMATION OF THE PROTEIN CHAIN 141 4.10 THE RAMACHANDRAN DIAGRAM
DEFINES THE RESTRICTIONS ON BACKBONE CONFORMATION 142 4.11 A HELICES AND
P STRANDS ARE FORMED WHEN
CONSECUTIVE RESIDUES ADOPT SIMILAR VALUES OF (J AND V* 143
4.12 LOOP SEGMENTS HAVE RESIDUES WITH VERY DIFFERENT VALUES OF § AND Y
146
4.13 A HELICES AND P STRANDS ARE OFTEN AMPHIPATHIC 147 4.14 SOME AMINO
ACIDS ARE PREFERRED OVER OTHERS IN A HELICES 149
IMAGE 4
XII DETAILED CONTENTS
C.
4.15
4.16
4.17
4.18
4.19
4.20
4.21
4.22 4.23
4.24
4.25 4.26
4.27
4.28
4.29
4.30
D.
4.31
4.32
4.33
4.34
4.35
4.36
4.37
4.38
4.39
4.40
4.41
STRUCTURAL MOTIFS AND DOMAINS IN SOLUBLE PROTEINS 150
SECONDARY STRUCTURE ELEMENTS ARE CONNECTED TO FORM SIMPLE MOTIFS 150
AMPHIPATHIC A HELICES CAN FORM DIMERIC STRUCTURES CALLED COILED COILS
153
HYDROPHOBIC SIDECHAINS IN COILED COILS ARE REPEATED IN A HEPTAD PATTERN
155
A HELICES THAT ARE INTEGRATED INTO COMPLEX PROTEIN STRUCTURES DO NOT
USUALLY FORM COILED COILS 156 THE SIDECHAINS OF A HELICES FORM RIDGES
AND GROOVES 157
A HELICES PACK AGAINST EACH OTHER WITH A LIMITED SET OF CROSSING ANGLES
157
STRUCTURES WITH ALTERNATING A HELICES AND P STRANDS ARE VERY COMMON 159
A/P BARRELS OCCUR IN MANY DIFFERENT ENZYMES 161 A/P OPEN-SHEET
STRUCTURES CONTAIN A HELICES ON BOTH SIDES OF THE P SHEET 162
PROTEINS WITH ANTIPARALLEL P SHEETS OFTEN FORM STRUCTURES CALLED P
BARRELS 162
UP-AND-DOWN P BARRELS HAVE A SIMPLE TOPOLOGY 163 UP-AND-DOWN P SHEETS
CAN FORM REPETITIVE STRUCTURES 163
GREEK KEY MOTIFS OCCUR FREQUENTLY IN ANTIPARALLEL P STRUCTURES 164
CERTAIN STRUCTURAL MOTIFS CAN BE REPEATED ALMOST ENDLESSLY TO FORM
ELONGATED STRUCTURES 165 CATALYTIC SITES ARE USUALLY LOCATED WITHIN CORE
ELEMENTS OF PROTEIN FOLDS 167
BINDING SITES ARE OFTEN LOCATED AT THE INTERFACES BETWEEN DOMAINS 168
STRUCTURAL PRINCIPLES OF MEMBRANE PROTEINS 169
LIPID BILAYERS FORM BARRIERS THAT ARE NEARLY IMPERMEABLE TO POLAR
MOLECULES 169
MEMBRANE PROTEINS HAVE DISTINCT REGIONS THAT INTERACT WITH THE LIPID
BILAYER 170
THE HYDROPHOBICITY OF THE LIPID BILAYER REQUIRES THE FORMATION OF
REGULAR SECONDARY STRUCTURE WITHIN THE MEMBRANE 171
THE MORE POLAR SIDECHAINS ARE RARELY FOUND WITHIN MEMBRANE-SPANNING A
HELICES, EXCEPT WHEN THEY ARE REQUIRED FOR SPECIFIC FUNCTIONS 172
TRANSMEMBRANE A HELICES CAN BE PREDICTED FROM
AMINO ACID SEQUENCES 174
HYDROPHOBICITY SCALES ARE USED TO IDENTIFY TRANSMEMBRANE HELICES 175
INTEGRAL MEMBRANE PROTEINS ARE STABILIZED BY VAN DER WAALS CONTACTS AND
HYDROGEN BONDS 177 PORINS CONTAIN P BARRELS THAT FORM TRANSMEMBRANE
CHANNELS 178
PUMPS AND TRANSPORTERS USE ENERGY TO MOVE MOLECULES ACROSS THE MEMBRANE
179
BACTERIORHODOPSIN USES LIGHT ENERGY TO PUMP PROTONS ACROSS THE MEMBRANE
180
A HYDROGEN-BONDED CHAIN OF WATER MOLECULES CAN SERVE AS A PROTON
CONDUCTING WIRE 180
4.42 CONFORMATIONAL CHANGES IN RETINAL IMPOSE DIRECTIONALITY TO PROTON
FLOW IN BACTERIORHODOPSIN 181
4.43 ACTIVE TRANSPORTERS CYCLE BETWEEN CONFORMATIONS THAT ARE OPEN TO
THE INTERIOR OR THE EXTERIOR OF THE CELL 183
4.44 ATP BINDING AND HYDROLYSIS PROVIDES THE DRIVING FORCE FOR THE
TRANSPORT OF SUGARS INTO THE CELL 184 SUMMARY 185
KEY CONCEPTS 187
PROBLEMS 188
FURTHER READING 189
CHAPTER 5 EVOLUTIONARY VARIATION IN PROTEINS 191
A. THE THERMODYNAMIC HYPOTHESIS 191 5.1 THE STRUCTURE OF A PROTEIN IS
DETERMINED BY ITS SEQUENCE 191
5.2 THE THERMODYNAMIC HYPOTHESIS WAS FIRST ESTABLISHED FOR AN ENZYME
KNOWN AS RIBO- NUCLEASE-A, WHICH CAN BE UNFOLDED AND FOLDED REVERSIBLY
192
5.3 BY COUNTING THE NUMBER OF POSSIBLE REARRANGEMENTS OF DISULFIDE
BONDS, WE CAN CONFIRM THAT RIBONUCLEASE-A IS COMPLETELY UNFOLDED BY UREA
AND REDUCING AGENTS 194
B. SEQUENCE COMPARISONS AND THE BLOSUM MATRIX 195
5.4 PROTEIN STRUCTURE IS CONSERVED DURING EVOLUTION WHILE AMINO ACID
SEQUENCES VARY 195
5.5 THE GLOBIN FOLD IS PRESERVED IN PROTEINS THAT SHARE VERY LITTLE
SEQUENCE SIMILARITY 198
5.6 SIMILARITIES IN PROTEIN SEQUENCES CAN BE QUANTIFIED BY CONSIDERING
THE FREQUENCIES WITH WHICH AMINO ACIDS ARE SUBSTITUTED FOR EACH OTHER IN
RELATED PROTEINS 201
5.7 THE BLOSUM MATRIX IS A COMMONLY USED SET OF AMINO ACID SUBSTITUTION
SCORES 201
5.8 THE FIRST STEP IN DERIVING SUBSTITUTION SCORES IS TO DETERMINE THE
FREQUENCIES OF AMINO ACID SUBSTITUTIONS AND CORRECT FOR AMINO ACID
ABUNDANCES 202
5.9 THE SUBSTITUTION SCORE IS DEFINED IN TERMS OF THE LOGARITHM OF THE
SUBSTITUTION LIKELIHOOD 204 5.10 THE BLOSUM SUBSTITUTION SCORES REFLECT
THE CHEMICAL PROPERTIES OF THE AMINO ACIDS 207 5.11 SUBSTITUTION SCORES
ARE USED TO ALIGN SEQUENCES
AND TO DETECT SIMILARITIES BETWEEN PROTEINS 208
C. STRUCTURAL VARIATION IN PROTEINS 209 5.12 SMALL BUT SIGNIFICANT
DIFFERENCES IN PROTEIN STRUCTURES ARISE FROM DIFFERENCES IN SEQUENCES
209 5.13 PROTEINS RETAIN A COMMON STRUCTURAL CORE AS
THEIR SEQUENCES DIVERGE 210
5.14 STRUCTURAL OVERLAP WITHIN THE COMMON CORE DECREASES AS THE
SEQUENCES OF PROTEINS DIVERGE 211 5.15 SEQUENCE COMPARISONS ALONE ARE
INSUFFICIENT TO ESTABLISH STRUCTURAL SIMILARITY BETWEEN DISTANTLY
RELATED PROTEINS 212
IMAGE 5
DETAILED CONTENTS XIII
5.16 THE AMINO ACIDS HAVE PREFERENCES FOR DIFFERENT ENVIRONMENTS IN
FOLDED PROTEINS 213
5.17 FOLD-RECOGNITION ALGORITHMS EVALUATE THE PROBABILITY THAT THE
SEQUENCE OF A PROTEIN IS COMPATIBLE WITH A KNOWN THREE-DIMENSIONAL
STRUCTURE 214
5.18 THE 3D-1D PROFILE METHOD MAPS THREE- DIMENSIONAL STRUCTURAL
INFORMATION ONTO A ONE- DIMENSIONAL SET OF ENVIRONMENTAL DESCRIPTORS 216
5.19 THE DATABASE OF KNOWN PROTEIN STRUCTURES IS
USED TO GENERATE A SCORING MATRIX THAT GIVES THE LIKELIHOOD OF FINDING
EACH AMINO ACID IN A PARTICULAR ENVIRONMENTAL CLASS 217
5.20 THE 3D-1D PROFILE METHOD MATCHES SEQUENCES WITH STRUCTURES 218
D. THE EVOLUTION OF MODULAR DOMAINS 220 5.21 DOMAINS ARE THE FUNDAMENTAL
UNIT OF PROTEIN EVOLUTION 220
5.22 DOMAINS CAN BE ORGANIZED INTO FAMILIES WITH SIMILAR FOLDS 220
5.23 THE NUMBER OF DISTINCT FOLD FAMILIES IS LIKELY TO BE LIMITED 224
5.24 PROTEIN DOMAINS ARE REMARKABLY TOLERANT OF CHANGES IN AMINO ACID
SEQUENCE, EVEN IN THE HYDROPHOBIC CORE 225
5.25 STRUCTURAL PLASTICITY IN PROTEIN DOMAINS INCREASES THE TOLERANCE TO
MUTATION 227
5.26 THE ROSSMANN FOLD IS FOUND IN MANY NUCLEOTIDE BINDING PROTEINS 228
5.27 THIOREDOXIN REDUCTASE AND GLUTATHIONE REDUCTASE ARE ENZYMES THAT
DIVERGED FROM A COMMON ANCESTOR, BUT THEIR ACTIVE SITES AROSE THROUGH
CONVERGENT EVOLUTION 230
SUMMARY 232
KEY CONCEPTS 234
PROBLEMS 235
FURTHER READING 237
PART II: ENERGY AND ENTROPY 238
CHAPTER 6 ENERGY AND INTERMOLECULAR FORCES 239
A. THERMODYNAMICS OF HEAT TRANSFER 240 6.1 IN ORDER TO KEEP TRACK OF
CHANGES IN ENERGY, WE DEFINE THE REGION OF INTEREST AS THE SYSTEM 240
6.2 ENERGY RELEASED BY CHEMICAL REACTIONS IS
CONVERTED TO HEAT AND WORK 242
6.3 THE FIRST LAW OF THERMODYNAMICS STATES THAT ENERGY IS CONSERVED 243
6.4 FOR A PROCESS OCCURRING UNDER CONSTANT PRESSURE CONDITIONS, THE HEAT
TRANSFERRED IS EQUAL TO THE CHANGE IN THE ENTHALPY OF THE SYSTEM 246
6.5 CHANGES IN ENERGY DO NOT ALWAYS INDICATE THE DIRECTION OF
SPONTANEOUS CHANGE 250
6.6 THE ISOTHERMAL EXPANSION OF AN IDEAL GAS OCCURS SPONTANEOUSLY EVEN
THOUGH THE ENERGY OF THE GAS DOES NOT CHANGE 251
B. HEAT CAPACITIES AND THE BOLTZMANN DISTRIBUTION 253
6.7 THE HEAT CAPACITY OF AN IDEAL MONATOMIC GAS IS CONSTANT 253
6.8 THE HEAT CAPACITY OF A MACROMOLECULAR SOLUTION INCREASES AND THEN
DECREASES WITH TEMPERATURE 257 6.9 THE POTENTIAL ENERGY OF A MOLECULAR
SYSTEM IS THE ENERGY STORED IN MOLECULES AND THEIR
INTERACTIONS 259
6.10 THE BOLTZMANN DISTRIBUTION DESCRIBES THE POPULATION OF MOLECULES IN
DIFFERENT ENERGY LEVELS 261
6.11 THE ENERGY REQUIRED TO BREAK INTERATOMIC INTERACTIONS IN FOLDED
MACROMOLECULES GIVES RISE TO THE PEAK IN HEAT CAPACITY 264
C. ENERGETICS OF INTERMOLECULAR INTERACTIONS 265
6.12 SIMPLIFIED ENERGY FUNCTIONS ARE USED TO CALCULATE MOLECULAR
POTENTIAL ENERGIES 265 6.13 EMPIRICAL POTENTIAL ENERGY FUNCTIONS ENABLE
RAPID CALCULATION OF MOLECULAR ENERGIES 266 6.14 THE ENERGIES OF
COVALENT BONDS ARE APPROXIMATED
BY FUNCTIONS SUCH AS THE MORSE POTENTIAL 267 6.15 OTHER TERMS IN THE
ENERGY FUNCTION DESCRIBE TORSION ANGLES AND THE DEFORMATIONS IN THE
ANGLES BETWEEN COVALENT BONDS 270
6.16 THE VAN DER WAALS ENERGY TERM DESCRIBES WEAK ATTRACTIONS AND STRONG
REPULSIONS BETWEEN ATOMS 272
6.17 ATOMS IN PROTEINS AND NUCLEIC ACIDS ARE PARTIALLY CHARGED 274
6.18 ELECTROSTATIC INTERACTIONS ARE GOVERNED BY COULOMB S LAW 275
6.19 HYDROGEN BONDS ARE AN IMPORTANT CLASS OF ELECTROSTATIC INTERACTIONS
277
6.20 EMPIRICAL ENERGY FUNCTIONS ARE USED IN COMPUTER PROGRAMS TO
CALCULATE MOLECULAR ENERGIES 279 6.21 INTERACTIONS WITH WATER WEAKEN THE
EFFECTIVE STRENGTHS OF HYDROGEN BONDS IN PROTEINS 281 6.22 THE PRESENCE
OF HYDROGEN-BONDING GROUPS
IN A PROTEIN IS IMPORTANT FOR SOLUBILITY AND SPECIFICITY 282
6.23 THE WATER SURROUNDING PROTEIN MOLECULES STRONGLY INFLUENCES
ELECTROSTATIC INTERACTIONS 283 6.24 THE SHAPES OF PROTEINS CHANGE THE
ELECTROSTATIC FIELDS GENERATED BY CHARGES WITHIN THE PROTEIN 285 SUMMARY
287
KEY CONCEPTS 288
PROBLEMS 289
FURTHER READING 292
CHAPTER 7 ENTROPY 293
A. COUNTING STATISTICS AND MULTIPLICITY 294 7.1 DIFFERENT SEQUENCES OF
OUTCOMES IN A SERIES OF COIN TOSSES HAVE EQUAL PROBABILITIES 294 7.2
WHEN CONSIDERING AGGREGATE OUTCOMES, THE
MOST LIKELY RESULT IS THE ONE THAT HAS MAXIMUM MULTIPLICITY 295
7.3 THE MULTIPLICITY OF AN OUTCOME OF COIN TOSSES CAN BE CALCULATED
USING A SIMPLE FORMULA INVOLVING FACTORIALS 297
IMAGE 6
XIV DETAILED CONTENTS
7.4 THE CONCEPT OF MULTIPLICITY IS BROADLY APPLICABLE IN BIOLOGY BECAUSE
A SERIES OF COIN FLIPS IS ANALOGOUS TO A COLLECTION OF MOLECULES IN
ALTERNATIVE STATES 300
7.5 THE BINDING OF LIGANDS TO A RECEPTOR CAN BE MONITORED BY
FLUORESCENCE MICROSCOPY 301 7.6 PASCAL S TRIANGLE DESCRIBES THE
MULTIPLICITY OF OUTCOMES FOR A SERIES OF BINARY EVENTS 302 7.7 THE
BINOMIAL DISTRIBUTION GOVERNS THE PROBABILITY
OF EVENTS WITH BINARY OUTCOMES 304
7.8 WHEN THE NUMBER OF EVENTS IS LARGE, STIRLING S APPROXIMATION
SIMPLIFIES THE CALCULATION OF THE MULTIPLICITY 306
7.9 THE RELATIVE PROBABILITY OF TWO OUTCOMES IS GIVEN BY THE RATIOS OF
THEIR MULTIPLICITIES 307 7.10 AS THE NUMBER OF EVENTS INCREASES, THE
LESS LIKELY OUTCOMES BECOME INCREASINGLY RARE 308 7.11 FOR COIN TOSSES,
OUTCOMES WITH EQUAL NUMBERS
OF HEADS AND TAILS HAVE MAXIMAL MULTIPLICITY 310 7.12 WHEN THE NUMBER OF
EVENTS IS VERY LARGE, THE PROBABILITY DISTRIBUTION IS WELL APPROXIMATED
BY A GAUSSIAN DISTRIBUTION 311
7.13 THE GAUSSIAN DISTRIBUTION IS CENTERED AT THE MEAN VALUE AND HAS A
WIDTH THAT IS PROPORTIONAL TO THE STANDARD DEVIATION 312
7.14 APPLICATION OF THE GAUSSIAN DISTRIBUTION ENABLES STATISTICAL
ANALYSIS OF A SERIES OF BINARY OUTCOMES
CHAPTER 8 LINKING ENERGY AND ENTROPY: THE BOLTZMANN DISTRIBUTION 341
B. ENTROPY
315
317
7.15 THE LOGARITHM OF THE MULTIPLICITY (IN I/I/) IS RELATED TO THE
ENTROPY 317
7.16 THE MULTIPLICITY OF A MOLECULAR SYSTEM IS THE NUMBER OF EQUIVALENT
CONFIGURATIONS OF THE MOLECULES (MICROSTATES) 318
7.17 THE MULTIPLICITY OF A SYSTEM INCREASES AS THE VOLUME INCREASES 319
7.18 FOR A LARGE NUMBER OF ATOMS, THE STATE WITH MAXIMAL MULTIPLICITY IS
THE STATE THAT IS OBSERVED AT EQUILIBRIUM 322
7.19 THE BOLTZMANN CONSTANT, K B , IS A PROPORTIONALITY CONSTANT LINKING
ENTROPY TO THE LOGARITHM OF THE MULTIPLICITY (IN W) 325
7.20 THE CHANGE IN ENTROPY IS RELATED TO THE HEAT TRANSFERRED DURING A
PROCESS 326
7.21 THE WORK DONE IN A NEAR-EQUILIBRIUM PROCESS IS GREATER THAN FOR A
NONEQUILIBRIUM PROCESS 327 7.22 THE WORK DONE IN A NEAR-EQUILIBRIUM
PROCESS IS RELATED TO THE CHANGE IN ENTROPY 329
7.23 THE STATISTICAL AND THERMODYNAMIC DEFINITIONS OF ENTROPY ARE
EQUIVALENT 330
7.24 THE SECOND LAW OF THERMODYNAMICS STATES THAT SPONTANEOUS CHANGE
OCCURS IN THE DIRECTION OF INCREASING ENTROPY 331
7.25 DIFFUSION ACROSS A SEMIPERMEABLE MEMBRANE CAN LEAD TO UNEQUAL
NUMBERS OF MOLECULES ON THE TWO SIDES OF THE MEMBRANE 332
SUMMARY KEY CONCEPTS PROBLEMS
FURTHER READING
335 336 337 339
A. ENERGY DISTRIBUTIONS AND ENTROPY 341 8.1 THE THERMODYNAMIC DEFINITION
OF THE ENTROPY PROVIDES A LINK TO EXPERIMENTAL OBSERVATIONS 341 8.2 THE
CONCEPT OF TEMPERATURE PROVIDES A
CONNECTION BETWEEN THE STATISTICAL AND THERMODYNAMIC DEFINITIONS OF
ENTROPY 343 8.3 ENERGY DISTRIBUTIONS DESCRIBE THE POPULATIONS OF
MOLECULES WITH DIFFERENT ENERGIES 344
8.4 THE MULTIPLICITY OF AN ENERGY DISTRIBUTION IS THE NUMBER OF
EQUIVALENT CONFIGURATIONS OF MOLECULES THAT RESULTS IN THE SAME ENERGY
DISTRIBUTION 344 8.5 THE MULTIPLICITY OF A SYSTEM WITH DIFFERENT
ENERGY LEVELS CAN BE CALCULATED BY COUNTING THE NUMBER OF EQUIVALENT
MOLECULAR REARRANGEMENTS OF ENERGY 347
B. THE BOLTZMANN DISTRIBUTION 350
8.6 FOR LARGE NUMBERS OF MOLECULES, A PROBABILISTIC EXPRESSION FOR THE
ENTROPY IS MORE CONVENIENT 350 8.7 THE MULTIPLICITY OF A SYSTEM CHANGES
WHEN ENERGY IS TRANSFERRED BETWEEN SYSTEMS 354 8.8 SYSTEMS IN THERMAL
CONTACT EXCHANGE HEAT
UNTIL THE COMBINED ENTROPY OF THE TWO SYSTEMS IS MAXIMAL 356
8.9 MANY ENERGY DISTRIBUTIONS ARE CONSISTENT WITH THE TOTAL ENERGY OF A
SYSTEM, BUT SOME HAVE HIGHER MULTIPLICITY THAN OTHERS 359
8.10 THE ENERGY DISTRIBUTION AT EQUILIBRIUM MUST HAVE AN EXPONENTIAL
FORM 360
8.11 THE PARTITION FUNCTION INDICATES THE ACCESSIBILITY OF THE HIGHER
ENERGY LEVELS OF THE SYSTEM 363 8.12 FOR LARGE NUMBERS OF MOLECULES,
NON-BOLTZMANN DISTRIBUTIONS OF THE ENERGY ARE HIGHLY UNLIKELY 367
C. ENTROPY AND TEMPERATURE 368
8.13 THE RATE OF CHANGE OF ENTROPY WITH RESPECT TO ENERGY IS RELATED TO
THE TEMPERATURE 368 8.14 THE STATISTICAL AND THERMODYNAMIC DEFINITIONS
OF THE ENTROPY ARE EQUIVALENT 375
SUMMARY 377
KEY CONCEPTS 378
PROBLEMS 379
FURTHER READING 381
PART III: FREE ENERGY 382
CHAPTER 9 FREE ENERGY 383
A. FREE ENERGY 384
9.1 THE COMBINED ENTROPY OF THE SYSTEM AND THE SURROUNDINGS INCREASES
FOR A SPONTANEOUS PROCESS 384
9.2 THE CHANGE IN ENTROPY OF THE SURROUNDINGS IS RELATED TO THE CHANGE
IN ENERGY AND VOLUME OF THE SYSTEM 386
9.3 THE GIBBS FREE ENERGY (G) OF THE SYSTEM ALWAYS DECREASES IN A
SPONTANEOUS PROCESS OCCURRING AT CONSTANT PRESSURE AND TEMPERATURE 387
IMAGE 7
DETAILED CONTENTS XV
9.4 THE HELMHOLTZ FREE ENERGY (A) DETERMINES THE DIRECTION OF
SPONTANEOUS CHANGE WHEN THE VOLUME IS CONSTANT
B. STANDARD FREE-ENERGY CHANGES STANDARD FREE-ENERGY CHANGES ARE DEFINED
WITH REFERENCE TO DEFINED STANDARD STATES 9.5
9.6
9.7
389
390
390
THE ZERO POINT OF THE FREE-ENERGY SCALE IS SET BY THE FREE ENERGY OF THE
ELEMENTS IN THEIR MOST STABLE FORMS 391
THERMODYNAMIC CYCLES ALLOW THE DETERMINATION OF THE FREE ENERGIES OF
FORMATION OF COMPLEX MOLECULES FROM SIMPLER ONES 392
THE FREE ENERGY OF FORMATION OF GLUCOSE IS OBTAINED BY CONSIDERING THREE
COMBUSTION REACTIONS 9.9
9.10
9.11
ENTHALPIES AND ENTROPIES OF FORMATION CAN BE COMBINED TO GIVE THE FREE
ENERGY OF FORMATION CALORIMETRIC MEASUREMENTS YIELD THE STANDARD
ENTHALPY CHANGES ASSOCIATED WITH COMBUSTION REACTIONS THE ENTROPY OF
FORMATION OF A COMPOUND IS DERIVED FROM HEAT CAPACITY MEASUREMENTS
C. FREE ENERGY AND WORK 9.12
394
395
396
396
398
EXPANSION WORK IS NOT THE ONLY KIND OF WORK THAT CAN BE DONE BY A SYSTEM
398
9.13 CHEMICAL WORK INVOLVES CHANGES IN THE NUMBERS OF MOLECULES 400
9.14 THE DECREASE IN THE GIBBS FREE ENERGY FOR A PROCESS IS THE MAXIMUM
AMOUNT OF NON- EXPANSION WORK THAT THE SYSTEM IS CAPABLE OF DOING UNDER
CONSTANT PRESSURE AND TEMPERATURE 9.15 THE COUPLING OF ATP HYDROLYSIS TO
WORK
UNDERLIES MANY PROCESSES IN BIOLOGY 9.16 THE SYNTHESIS OF ATP IS COUPLED
TO THE MOVEMENT OF IONS ACROSS THE MEMBRANE, DOWN
A CONCENTRATION GRADIENT SUMMARY KEY CONCEPTS PROBLEMS FURTHER READING
CHAPTER 10 CHEMICAL POTENTIAL AND THE DRIVE TO EQUILIBRIUM A. CHEMICAL
POTENTIAL
400
402
405 408 409 409 411
413
413
10.1 THE CHEMICAL POTENTIAL OF A MOLECULAR SPECIES IS THE MOLAR FREE
ENERGY OF THAT SPECIES 414 10.2 MOLECULES MOVE SPONTANEOUSLY FROM
REGIONS OF HIGH CHEMICAL POTENTIAL TO REGIONS OF LOW
CHEMICAL POTENTIAL 414
10.3 BIOCHEMICAL REACTIONS ARE ASSUMED TO OCCUR IN IDEAL AND DILUTE
SOLUTIONS, WHICH SIMPLIFIES THE CALCULATION OF THE CHEMICAL POTENTIAL
416 10.4 THE CHEMICAL POTENTIAL IS PROPORTIONAL TO THE
LOGARITHM OF THE CONCENTRATION 417
10.5 CHEMICAL POTENTIALS AT ARBITRARY CONCENTRATIONS ARE CALCULATED WITH
REFERENCE TO STANDARD CONCENTRATIONS
B. EQUILIBRIUM CONSTANTS
421
422
10.6 THE CHEMICAL POTENTIALS OF THE REACTANTS AND PRODUCTS ARE BALANCED
AT EQUILIBRIUM 422
10.7 THE CONCENTRATIONS OF REACTANTS AND PRODUCTS AT EQUILIBRIUM DEFINE
THE EQUILIBRIUM CONSTANT (K), WHICH IS RELATED TO THE STANDARD FREE
ENERGY CHANGE (AG) FOR THE REACTION 424 10.8 EQUILIBRIUM CONSTANTS CAN
BE USED TO CALCULATE
THE EXTENT OF REACTION AT EQUILIBRIUM 425
10.9 THE FREE-ENERGY CHANGE FOR THE REACTION (AG), NOT THE STANDARD
FREE-ENERGY CHANGE (AG), DETERMINES THE DIRECTION OF SPONTANEOUS CHANGE
426
10.10 THE RATIO OF THE REACTION QUOTIENT (Q) TO THE EQUILIBRIUM CONSTANT
(K) DETERMINES THE THERMODYNAMIC DRIVE OF A REACTION 427
10.11 ATP CONCENTRATIONS ARE MAINTAINED AT HIGH LEVELS IN CELLS, THEREBY
INCREASING THE DRIVING FORCE FOR ATP HYDROLYSIS 427
C, ACID-BASE EQUILIBRIA 428
10.12 THE HENDERSON-HASSELBALCH EQUATION RELATES THE PH OF A SOLUTION OF
A WEAK ACID TO THE CONCENTRATIONS OF THE ACID AND ITS CONJUGATE BASE 429
10.13 THE PROTON CONCENTRATION ([H + ]) IN PURE WATER AT ROOM
TEMPERATURE CORRESPONDS TO A PH VALUE OF 7.0 430
10.14 THE TEMPERATURE DEPENDENCE OF THE EQUILIBRIUM CONSTANT ALLOWS US
TO DETERMINE THE VALUES OF AH 0 AND AS 0 431
10.15 WEAK ACIDS, SUCH AS ACETIC ACID, DISSOCIATE VERY LITTLE IN WATER
432
10.16 SOLUTIONS OF WEAK ACIDS AND THEIR CONJUGATE BASES ACT AS BUFFERS
433
10.17 THE CHARGES ON BIOLOGICAL MACROMOLECULES ARE AFFECTED BY THE PH
435
10.18 THE CHARGE ON AN AMINO ACID SIDECHAIN CAN BE ALTERED BY
INTERACTIONS IN THE FOLDED PROTEIN 436
D. FREE-ENERGY CHANGES IN PROTEIN FOLDING 438
10.19 THE PROTEIN FOLDING REACTION IS SIMPLIFIED BY IGNORING
INTERMEDIATE CONFORMATIONS 438 10.20 PROTEIN FOLDING RESULTS FROM A
BALANCE BETWEEN ENERGY AND ENTROPY 439
10.21 THE ENTROPY OF THE UNFOLDED PROTEIN CHAIN IS PROPORTIONAL TO THE
LOGARITHM OF THE NUMBER OF CONFORMATIONS OF THE CHAIN 440
10.22 THE NUMBER OF CONFORMATIONS OF THE UNFOLDED CHAIN CAN BE ESTIMATED
BY COUNTING THE NUMBER OF LOW-ENERGY TORSIONAL ISOMERS 442
10.23 THE FREE-ENERGY CHANGE OPPOSES PROTEIN FOLDING IF THE ENTROPY OF
WATER MOLECULES IS NOT CONSIDERED 443
10.24 PROTEIN FOLDING IS DRIVEN BY AN INCREASE IN WATER ENTROPY 444
10.25 CALORIMETRIC MEASUREMENTS ALLOW THE EXPERIMENTAL DETERMINATION OF
THE FREE ENERGY OF PROTEIN FOLDING 446
10.26 THE HEAT CAPACITY OF A PROTEIN SOLUTION DEPENDS ON THE RELATIVE
POPULATION OF FOLDED AND UNFOLDED MOLECULES, AND ON THE ENERGY REQUIRED
TO UNFOLD THE PROTEIN 446
IMAGE 8
XVI DETAILED CONTENTS
10.27 THE AREA UNDER THE PEAK IN THE MELTING CURVE IS THE ENTHALPY
CHANGE FOR UNFOLDING AT THE MELTING TEMPERATURE 448
10.28 THE HEAT CAPACITIES OF THE FOLDED AND UNFOLDED PROTEIN ALLOW THE
DETERMINATION OF AH 0 AND AS 0 FOR UNFOLDING AT ANY TEMPERATURE 449
10.29 FOLDED PROTEINS BECOME UNSTABLE AT VERY LOW TEMPERATURE BECAUSE OF
CHANGES IN AH 0 AND AS 0 SUMMARY
KEY CONCEPTS PROBLEMS FURTHER READING
CHAPTER 11 VOLTAGES AND FREE ENERGY 459
A. OXIDATION-REDUCTION REACTIONS IN BIOLOGY 459
11.1 REACTIONS INVOLVING THE TRANSFER OF ELECTRONS ARE REFERRED TO AS
OXIDATION-REDUCTION REACTIONS 459 11.2 BIOLOGICALLY IMPORTANT
REDOX-ACTIVE METALS ARE BOUND TO PROTEINS 460
11.3 NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD+) IS AN IMPORTANT MEDIATOR
OF REDOX REACTIONS IN BIOLOGY 460
11.4 FLAVINS AND QUINONES CAN UNDERGO OXIDATION OR REDUCTION IN TWO
STEPS OF ONE ELECTRON EACH 461 11.5 THE OXIDATION OF GLUCOSE IS COUPLED
TO THE GENERATION OF NADH AND FADH 2 463
11.6 MITOCHONDRIA ARE CELLULAR COMPARTMENTS IN WHICH NADH AND FADH 2 ARE
USED TO GENERATE ATP 465
11.7 ABSORPTION OF LIGHT CREATES MOLECULES WITH HIGH REDUCING POWER IN
PHOTOSYNTHESIS 467
B. REDUCTION POTENTIALS AND FREE ENERGY 469
11.8 ELECTROCHEMICAL CELLS CAN BE CONSTRUCTED BY LINKING TWO REDOX
COUPLES 470
11.9 THE VOLTAGE GENERATED BY AN ELECTROCHEMICAL CELL WITH THE REACTANTS
AT STANDARD CONDITIONS IS KNOWN AS THE STANDARD CELL POTENTIAL 473
11.10 THE ELECTRIC POTENTIAL DIFFERENCE (VOLTAGE) BETWEEN TWO POINTS IS
THE WORK DONE IN MOVING A UNIT CHARGE BETWEEN THE TWO POINTS 474
11.11 STANDARD REDUCTION POTENTIALS ARE RELATED TO THE STANDARD
FREE-ENERGY CHANGE OF THE REDOX REACTION UNDERLYING THE ELECTROCHEMICAL
CELL 475
11.12 ELECTRODE POTENTIALS ARE MEASURED RELATIVE TO A STANDARD HYDROGEN
ELECTRODE 477
11.13 TABULATED VALUES OF STANDARD ELECTRODE POTENTIALS ALLOW READY
CALCULATION OF THE STANDARD POTENTIAL OF AN ELECTROCHEMICAL CELL 478
11.14 THE NERNST EQUATION DESCRIBES HOW THE
POTENTIAL CHANGES WITH THE CONCENTRATIONS OF THE REDOX REACTANTS 480
11.15 THE STANDARD STATE FOR REDUCTION POTENTIALS IN BIOCHEMISTRY IS PH
7 480
C. ION PUMPS AND CHANNELS IN NEURONS 481 11.16 NEURONAL CELLS USE
ELECTRICAL SIGNALS TO TRANSMIT INFORMATION 482
452 453 455 456 457
11.19
11.20
11.21
11.17 AN ELECTRICAL POTENTIAL DIFFERENCE ACROSS THE MEMBRANE IS
ESSENTIAL FOR THE FUNCTIONING OF ALL CELLS 484
11.18 THE SODIUM-POTASSIUM PUMP HYDROLYZES ATP TO MOVE NA + IONS OUT OF
THE CELL WITH THE COUPLED MOVEMENT OF K + IONS INTO THE CELL 486 SODIUM
AND POTASSIUM CHANNELS ALLOW IONS
TO MOVE QUICKLY ACROSS THE MEMBRANE 487 SODIUM AND POTASSIUM CHANNELS
CONTAIN A CONSERVED TETRAMERIC PORE DOMAIN 489
A LARGE VESTIBULE WITHIN THE CHANNEL REDUCES THE DISTANCE OVER WHICH
IONS HAVE TO MOVE WITHOUT ASSOCIATED WATER MOLECULES 490
11.22 CARBONYL GROUPS IN THE SELECTIVITY FILTER PROVIDE SPECIFICITY FOR
K + IONS BY SUBSTITUTING FOR THE INNER-SPHERE WATERS 491
11.23 RAPID TRANSIT OF K + IONS THROUGH THE CHANNEL IS FACILITATED BY
HOPPING BETWEEN ISOENERGETIC BINDING SITES 492
D. THE TRANSMISSION OF ACTION POTENTIALS IN NEURONS 493
11.24 THE ASYMMETRIC DISTRIBUTION OF IONS ACROSS THE CELL MEMBRANE
GENERATES AN EQUILIBRIUM MEMBRANE POTENTIAL 493
11.25 THE NERNST EQUATION RELATES THE EQUILIBRIUM MEMBRANE POTENTIAL TO
THE CONCENTRATIONS OF IONS INSIDE AND OUTSIDE THE CELL 494
11.26 CELL MEMBRANES ACT AS ELECTRICAL CAPACITORS 496 11.27 THE
DEPOLARIZATION OF THE MEMBRANE IS A KEY STEP IN INITIATING A NEURONAL
SIGNAL 498
11.28 MEMBRANE POTENTIALS ARE ALTERED BY THE MOVEMENT OF RELATIVELY FEW
IONS, ENABLING RAPID AXONAL TRANSMISSION 499
11.29 THE PROPAGATION OF VOLTAGE CHANGES CAN BE UNDERSTOOD BY TREATING
THE AXON AS AN ELECTRICAL CIRCUIT 500
11.30 THE PROPAGATION OF CHANGES IN MEMBRANE POTENTIAL IN THE AXON ARE
DESCRIBED BY THE CABLE EQUATION 501
11.31 THE RESTING MEMBRANE POTENTIAL IS DETERMINED BY A COMBINATION OF
THE BASAL CONDUCTANCES OF POTASSIUM AND SODIUM CHANNELS 505
11.32 THE PROPAGATION OF A VOLTAGE SPIKE WITHOUT TRIGGERING
VOLTAGE-GATED ION CHANNELS IS KNOWN AS PASSIVE SPREAD 506
11.33 IF MEMBRANE CURRENTS ARE NEGLECTED, THEN THE CABLE EQUATION IS
ANALOGOUS TO A DIFFUSION EQUATION 507
11.34 LEAKAGE THROUGH OPEN ION CHANNELS LIMITS THE SPREAD OF A VOLTAGE
PERTURBATION 509
11.35 THE TIME TAKEN TO DEVELOP A MEMBRANE POTENTIAL IS DETERMINED BY
THE CONDUCTANCE OF THE MEMBRANE AND ITS CAPACITANCE 510
11.36 MYELINATION OF MAMMALIAN NEURONS FACILITATES THE TRANSMISSION OF
ACTION POTENTIALS 513
11.37 ACTION POTENTIALS ARE REGENERATED PERIODICALLY AS THEY TRAVEL DOWN
THE AXON 514
11.38 A POSITIVELY CHARGED SENSOR IN VOLTAGE-GATED ION CHANNELS MOVES
ACROSS THE MEMBRANE UPON DEPOLARIZATION 517
IMAGE 9
DETAILED CONTENTS XVII
11.39 THE STRUCTURES OF VOLTAGE-GATED K + CHANNELS SHOW THAT THE VOLTAGE
SENSORS FORM PADDLE-LIKE STRUCTURES THAT SURROUND THE CORE OF THE
CHANNEL 11.40 THE CRYSTAL STRUCTURE OF A VOLTAGE-GATED
K + CHANNEL SUGGESTS HOW THE VOLTAGE SENSOR OPENS AND CLOSES THE CHANNEL
SUMMARY KEY CONCEPTS PROBLEMS FURTHER READING
PART IV: MOLECULAR INTERACTIONS
CHAPTER 12 MOLECULAR RECOGNITION: THE THERMODYNAMICS OF BINDING A.
THERMODYNAMICS OF MOLECULAR INTERACTIONS
12.1 THE AFFINITY OF A PROTEIN FOR A LIGAND IS CHARACTERIZED BY THE
DISSOCIATION CONSTANT, K D 12.2 THE VALUE OF K D CORRESPONDS TO THE
CONCENTRATION OF FREE LIGAND AT WHICH THE PROTEIN IS HALF SATURATED 12.3
THE DISSOCIATION CONSTANT IS A DIMENSIONLESS NUMBER, BUT IS COMMONLY
REFERRED TO IN
CONCENTRATION UNITS 12.4 DISSOCIATION CONSTANTS ARE DETERMINED
EXPERIMENTALLY USING BINDING ASSAYS 12.5 BINDING ISOTHERMS PLOTTED WITH
LOGARITHMIC
AXES ARE COMMONLY USED TO DETERMINE THE DISSOCIATION CONSTANT 12.6 WHEN
THE LIGAND IS IN GREAT EXCESS OVER THE PROTEIN, THE FREE LIGAND
CONCENTRATION, [L], IS
ESSENTIALLY EQUAL TO THE TOTAL LIGAND CONCENTRATION 12.7 SCATCHARD
ANALYSIS MAKES IT POSSIBLE TO ESTIMATE THE VALUE OF K D WHEN THE
CONCENTRATION OF THE RECEPTOR IS UNKNOWN 12.8 SCATCHARD ANALYSIS CAN BE
APPLIED TO UNPURIFIED PROTEINS 12.9 SATURABLE BINDING IS A HALLMARK OF
SPECIFIC
BINDING INTERACTIONS 12.10 THE VALUE OF THE DISSOCIATION CONSTANT, K D ,
DEFINES THE LIGAND CONCENTRATION RANGE OVER WHICH THE PROTEIN SWITCHES
FROM UNBOUND
TO BOUND
12.11 THE DISSOCIATION CONSTANT FOR A PHYSIOLOGICAL LIGAND IS USUALLY
CLOSE TO THE NATURAL CONCENTRATION OF THE LIGAND
B. DRUG BINDING BY PROTEINS 12.12 MOST DRUGS ARE DEVELOPED BY OPTIMIZING
THE INHIBITION OF PROTEIN TARGETS 12.13 SIGNALING MOLECULES ARE PROTEIN
TARGETS IN
CANCER DRUG DEVELOPMENT 12.14 MOST SMALL MOLECULE DRUGS WORK BY
DISPLACING A NATURAL LIGAND FOR A PROTEIN 12.15 THE BINDING OF DRUGS TO
THEIR TARGET PROTEINS
OFTEN RESULTS IN CONFORMATIONAL CHANGES IN THE PROTEIN
520
521 524 525 526 527
530
531
531
533
535
537
537
540
542
543
544
546
A. 13.1
13.2
13.3
13.4
13.5
13.6
13.7
13.8
546
548
549
549
549
552
556
12.16 INDUCED-FIT BINDING OCCURS THROUGH SELECTION BY THE LIGAND OF ONE
AMONG MANY PREEXISTING CONFORMATIONS OF THE PROTEIN 557
12.17 CONFORMATIONAL CHANGES IN THE PROTEIN UNDERLIE THE SPECIFICITY OF
A CANCER DRUG KNOWN AS IMATINIB 559
12.18 CONFORMATIONAL CHANGES IN THE TARGET PROTEIN CAN WEAKEN THE
AFFINITY OF AN INHIBITOR 560
12.19 THE STRENGTH OF NONCOVALENT INTERACTIONS USUALLY CORRELATES WITH
HYDROPHOBIC INTERACTIONS 562 12.20 CHOLESTEROL-LOWERING DRUGS KNOWN AS
STATINS TAKE ADVANTAGE OF HYDROPHOBIC INTERACTIONS
TO BLOCK THEIR TARGET ENZYME 563
12.21 THE APPARENT AFFINITY OF A COMPETITIVE INHIBITOR FOR A PROTEIN IS
REDUCED BY THE PRESENCE OF THE NATURAL LIGAND 566
12.22 ENTROPY LOST BY DRUG MOLECULES UPON BINDING IS REGAINED THROUGH
THE HYDROPHOBIC EFFECT AND THE RELEASE OF PROTEIN-BOUND WATER MOLECULES
569 12.23 ISOTHERMAL TITRATION CALORIMETRY ALLOWS US TO
DETERMINE THE ENTHALPIC AND ENTROPIC COMPONENTS OF THE BINDING FREE
ENERGY 573 SUMMARY 576
KEY CONCEPTS 578
PROBLEMS 578
FURTHER READING 580
CHAPTER 13 SPECIFICITY OF MACROMOLECULAR RECOGNITION 581
AFFINITY AND SPECIFICITY 581
BOTH AFFINITY AND SPECIFICITY ARE IMPORTANT IN INTERMOLECULAR
INTERACTIONS 581
PROTEINS OFTEN HAVE TO CHOOSE BETWEEN SEVERAL CLOSELY RELATED TARGETS
582
SPECIFICITY IS DEFINED IN TERMS OF RATIOS OF DISSOCIATION CONSTANTS 584
THE SPECIFICITY OF BINDING DEPENDS ON THE CONCENTRATION OF LIGAND 585
FRACTIONAL OCCUPANCY AND SPECIFICITY ARE IMPORTANT FOR ACTIVITIES
RESULTING FROM BINDING 587 MOST MACROMOLECULAR INTERACTIONS ARE A
COMPROMISE BETWEEN AFFINITY AND SPECIFICITY 587
FIBROBLAST GROWTH FACTORS VARY CONSIDERABLY IN THEIR AFFINITIES FOR
RECEPTORS 588
THE RECOGNITION OF DNA BY TRANSCRIPTION FACTORS INVOLVES DISCRIMINATION
BETWEEN A VERY LARGE NUMBERS OF OFF-TARGET BINDING SITES 590
13.9 LOWERING THE AFFINITY OF LAC REPRESSOR FOR THE OPERATOR SWITCHES ON
TRANSCRIPTION 591
B. PROTEIN-PROTEIN INTERACTIONS 593 13.10 PROTEIN-PROTEIN COMPLEXES
INVOLVE INTERFACES BETWEEN TWO FOLDED DOMAINS OR BETWEEN A DOMAIN AND A
PEPTIDE SEGMENT 593
13.11 SH2 DOMAINS ARE SPECIFIC FOR PEPTIDES CONTAINING PHOSPHOTYROSINE
595
13.12 INDIVIDUAL SH2 DOMAINS CANNOT DISCRIMINATE SHARPLY BETWEEN
DIFFERENT PHOSPHOTYROSINE- CONTAINING SEQUENCES 596
13.13 COMBINATIONS OF PEPTIDE RECOGNITION DOMAINS HAVE HIGHER
SPECIFICITY THAN INDIVIDUAL DOMAINS 597
IMAGE 10
XVIII DETAILED CONTENTS
13.14 PROTEIN-PROTEIN INTERFACES USUALLY HAVE A SMALL HYDROPHOBIC CORE
599
13.15 A TYPICAL PROTEIN-PROTEIN INTERFACE BURIES ABOUT 700 TO 800 A 2 OF
SURFACE AREA ON EACH PROTEIN 600 13.16 WATER MOLECULES FORM
HYDROGEN-BONDED NETWORKS AT PROTEIN-PROTEIN INTERFACES 601 13.17 THE
INTERACTION BETWEEN GROWTH HORMONE AND
ITS RECEPTOR IS A MODEL FOR UNDERSTANDING PROTEIN-PROTEIN INTERACTIONS
602
13.18 THE MAJOR GROWTH HORMONE-RECEPTOR INTERFACE CONTAINS MANY TYPES OF
INTERACTIONS 603
13.19 THE INTERFACE BETWEEN GROWTH HORMONE AND ITS RECEPTOR CONTAINS HOT
SPOTS OF BINDING AFFINITY, WHICH DOMINATE THE INTERACTION 605 13.20
RESIDUES THAT DO NOT CONTRIBUTE TO BINDING
AFFINITY MAY BE IMPORTANT FOR SPECIFICITY 606 13.21 THE DESOLVATION OF
POLAR GROUPS AT INTERFACES MAKES A LARGE CONTRIBUTION TO THE FREE ENERGY
OF BINDING 607
C. RECOGNITION OF NUCLEIC ACIDS BY PROTEINS 610
13.22 COMPLEMENTARITY IN BOTH ELECTROSTATICS AND SHAPE IS AN IMPORTANT
ASPECT OF THE RECOGNITION OF DOUBLE-HELICAL DNA AND RNA 610
13.23 PROTEINS DISTINGUISH BETWEEN DNA AND RNA DOUBLE HELICES BY
RECOGNIZING DIFFERENCES IN THE GEOMETRY OF THE GROOVES 612
13.24 PROTEINS RECOGNIZE DNA SEQUENCES BY BOTH DIRECT CONTACTS AND
INDUCED CONFORMATIONAL CHANGES IN DNA 613
13.25 HYDROGEN BONDING IS A KEY DETERMINANT OF SPECIFICITY AT
DNA-PROTEIN INTERFACES 614
13.26 WATER MOLECULES CAN FORM SPECIFIC HYDROGEN- BOND BRIDGES BETWEEN
PROTEIN AND DNA 615 13.27 ARGININE INTERACTIONS WITH THE MINOR GROOVE
CAN PROVIDE SEQUENCE SPECIFICITY THROUGH
SHAPE RECOGNITION 616
13.28 DNA STRUCTURAL CHANGES INDUCED BY BINDING VARY WIDELY 617
13.29 PROTEINS THAT BIND DNA AS DIMERS DO SO WITH HIGHER AFFINITY THAN
IF THEY WERE MONOMERS 618 13.30 LINKED DNA BINDING MODULES CAN INCREASE
BINDING AFFINITY AND SPECIFICITY 619
13.31 COOPERATIVE BINDING OF PROTEINS ALSO ENHANCES SPECIFICITY 620
13.32 PROTEINS THAT RECOGNIZE SINGLE-STRANDED RNA INTERACT EXTENSIVELY
WITH THE BASES 623
13.33 STACKING INTERACTIONS BETWEEN AMINO ACID SIDECHAINS AND NUCLEOTIDE
BASES ARE AN IMPORTANT ASPECT OF RNA RECOGNITION 625
SUMMARY 627
KEY CONCEPTS 628
PROBLEMS 629
FURTHER READING 630
CHAPTER 14 ALLOSTERY 633
A. ULTRASENSITIVE OF MOLECULAR RESPONSES 633
14.1 MOLECULAR OUTPUTS THAT DEPEND ON INDEPENDENT BINDING EVENTS SWITCH
FROM ON TO OFF OVER A 100-FOLD RANGE IN INPUT STRENGTH 633
14.2 THE RESPONSE OF MANY BIOLOGICAL SYSTEMS IS ULTRASENSITIVE, WITH THE
SWITCH FROM OFF TO ON OCCURRING OVER A LESS THAN 100-FOLD RANGE IN
CONCENTRATION 634
14.3 COOPERATIVITY AND ALLOSTERY ARE FEATURES OF MANY ULTRASENSITIVE
SYSTEMS 636
14.4 BACTERIAL MOVEMENT TOWARDS ATTRACTANTS AND AWAY FROM REPELLANTS IS
GOVERNED BY SIGNALING PROTEINS THAT BIND TO THE FLAGELLAR MOTOR 638 14.5
THE FLAGELLAR MOTOR SWITCHES TO CLOCKWISE
ROTATION WHEN THE CONCENTRATION OF CHEY INCREASES OVER A NARROW RANGE
639
14.6 THE RESPONSE OF THE FLAGELLAR MOTOR TO CONCENTRATIONS OF CHEY IS
ULTRASENSITIVE 640 14.7
14.8
14.9
THE MAP KINASE PATHWAY INVOLVES THE SEQUENTIAL ACTIVATION OF A SET OF
THREE PROTEIN KINASES 641
PHOSPHORYLATION CONTROLS THE ACTIVITY OF PROTEIN KINASES BY ALLOSTERIC
MODULATION OF THE STRUCTURE OF THE ACTIVE SITE THE SEQUENTIAL
PHOSPHORYLATION OF THE MAP
KINASES LEADS TO AN ULTRASENSITIVE SIGNALING SWITCH
B. ALLOSTERY IN HEMOGLOBIN
642
643 645
14.10 ALLOSTERIC PROTEINS EXHIBIT POSITIVE OR NEGATIVE COOPERATIVITY 645
14.11 THE HEME GROUP IN HEMOGLOBIN BINDS OXYGEN REVERSIBLY 646
14.12 HEMOGLOBIN INCREASES THE SOLUBILITY OF OXYGEN IN BLOOD AND MAKES
ITS TRANSPORT TO THE TISSUES MORE EFFICIENT 647
14.13 HEMOGLOBIN UNDERGOES CONFORMATIONAL CHANGES AS IT BINDS TO AND
RELEASES OXYGEN 649 14.14 THE SIGMOID BINDING ISOTHERM FOR AN ALLOSTERIC
PROTEIN ARISES FROM SWITCHING BETWEEN LOW-
AND HIGH-AFFINITY BINDING ISOTHERMS 649
14.15 THE DEGREE OF COOPERATIVITY BETWEEN BINDING SITES IN AN ALLOSTERIC
PROTEIN IS CHARACTERIZED BY THE HILL COEFFICIENT 650
14.16 THE TERTIARY STRUCTURE OF EACH HEMOGLOBIN SUBUNIT CHANGES UPON
OXYGEN BINDING 653 14.17 CHANGES IN THE TERTIARY STRUCTURE OF EACH
SUBUNIT ARE COUPLED TO A CHANGE IN THE
QUATERNARY STRUCTURE OF HEMOGLOBIN 655
14.18 THE HEMOGLOBIN TETRAMER IS ALWAYS IN EQUILIBRIUM BETWEEN R AND T
STATES, AND OXYGEN BINDING BIASES THE EQUILIBRIUM 658
14.19 BISPHOSPHOGLYCERATE (BPG) STABILIZES THE T-STATE QUATERNARY
STRUCTURE OF HEMOGLOBIN 660
14.20 THE LOW PH IN VENOUS BLOOD STABILIZES THE T-STATE QUATERNARY
STRUCTURE OF HEMOGLOBIN 661
14.21 HEMOGLOBINS ACROSS EVOLUTION HAVE ACQUIRED DISTINCT ALLOSTERIC
MECHANISMS FOR ACHIEVING ULTRASENSITIVITY 662
14.22 ALLOSTERIC MECHANISMS ARE LIKELY TO EVOLVE BY THE ACCRETION OF
RANDOM MUTATIONS IN COLOCALIZED PROTEINS 663
SUMMARY 667
KEY CONCEPTS 668
PROBLEMS 668
FURTHER READING 670
IMAGE 11
DETAILED CONTENTS XIX
PART V: KINETICS AND CATALYSIS 672
CHAPTER 15 THE RATES OF MOLECULAR PROCESSES 673
A. GENERAL KINETIC PRINCIPLES 675
15.1 THE RATE OF REACTION DESCRIBES HOW FAST CONCENTRATIONS CHANGE WITH
TIME 675
15.2 THE RATES OF INTERMOLECULAR REACTIONS DEPEND ON THE CONCENTRATIONS
OF THE REACTANTS 676 15.3 RATE LAWS DEFINE THE RELATIONSHIP BETWEEN THE
REACTION RATES AND CONCENTRATIONS 676 15.4 THE DEPENDENCE OF THE RATE
LAW ON THE
CONCENTRATIONS OF REACTANTS DEFINES THE ORDER OF THE REACTION 678
15.5 THE INTEGRATION OF RATE EQUATIONS PREDICTS THE TIME DEPENDENCE OF
CONCENTRATIONS 679
15.6 REACTANTS DISAPPEAR LINEARLY WITH TIME FOR A ZERO-ORDER REACTION
680
15.7 THE CONCENTRATION OF REACTANT DECREASES EXPONENTIALLY WITH TIME FOR
A FIRST-ORDER REACTION 680
15.8 THE REACTANTS DECAY MORE SLOWLY IN SECOND- ORDER REACTIONS THAN IN
FIRST-ORDER REACTIONS, BUT THE DETAILS DEPEND ON THE PARTICULAR TYPE OF
REACTION AND THE CONDITIONS 15.9 THE HALF-LIFE FOR A REACTION PROVIDES A
MEASURE
OF THE SPEED OF THE REACTION 682
15.10 FOR REACTIONS WITH INTERMEDIATE STEPS, THE SLOWEST STEP DETERMINES
THE OVERALL RATE 683
B. REVERSIBLE REACTIONS, STEADY STATES, AND EQUILIBRIUM 15.11 THE
FORWARD AND REVERSE RATES MUST BOTH BE CONSIDERED FOR A REVERSIBLE
REACTION 15.12 THE ON AND OFF RATES OF LIGAND BINDING CAN BE
MEASURED BY MONITORING THE APPROACH TO EQUILIBRIUM 15.13 STEADY-STATE
REACTIONS ARE IMPORTANT IN METABOLISM 15.14 FOR REACTIONS WITH
ALTERNATIVE PRODUCTS, THE
RELATIVE VALUES OF RATE CONSTANTS DETERMINE THE DISTRIBUTION OF PRODUCTS
MEASURING FLUORESCENCE PROVIDES AN EASY WAY TO MONITOR KINETICS 15.15
15.16 FLUORESCENCE MEASUREMENTS CAN BE CARRIED OUT
15.17 UNDER STEADY-STATE CONDITIONS FLUORESCENCE QUENCHERS PROVIDE A WAY
TO DETECT WHETHER A FLUOROPHORE ON A PROTEIN IS ACCESSIBLE TO THE
SOLVENT 15.18 THE COMBINATION OF FORWARD AND REVERSE RATE
CONSTANTS IS RELATED TO THE EQUILIBRIUM CONSTANT 15.19 RELAXATION
METHODS PROVIDE A WAY TO OBTAIN RATE CONSTANTS FOR REVERSIBLE REACTIONS
15.20 TEMPERATURE JUMP EXPERIMENTS CAN BE USED
TO DETERMINE THE ASSOCIATION AND DISSOCIATION RATE CONSTANTS FOR
DIMERIZATION 15.21 THE RATE CONSTANTS FOR A CYCLIC SET OF REACTIONS ARE
COUPLED
C. FACTORS THAT AFFECT THE RATE CONSTANT
15.22 CATALYSTS ACCELERATE THE RATES OF CHEMICAL REACTIONS WITHOUT BEING
CONSUMED IN THE PROCESS 705
15.23 RATE LAWS FOR REACTIONS USUALLY MUST BE DETERMINED EXPERIMENTALLY
706
15.24 THE HYDROLYSIS OF SUCROSE PROVIDES AN EXAMPLE OF HOW A REACTION
MECHANISM IS ANALYZED 707 15.25 THE FASTEST POSSIBLE REACTION RATE IS
DETERMINED BY THE DIFFUSION-LIMITED RATE OF COLLISION 709 15.26 MOST
REACTIONS OCCUR MORE SLOWLY THAN THE
DIFFUSION-LIMITED RATE 710
15.27 THE ACTIVATION ENERGY IS THE MINIMUM ENERGY REQUIRED TO CONVERT
REACTANTS TO PRODUCTS DURING A COLLISION BETWEEN MOLECULES 711
15.28 THE REACTION RATE DEPENDS EXPONENTIALLY ON THE ACTIVATION ENERGY
712
15.29 TRANSITION STATE THEORY LINKS KINETICS TO THERMODYNAMIC CONCEPTS
715
15.30 CATALYSTS CAN WORK BY DECREASING THE ACTIVATION ENERGY, BY
INCREASING THE PREEXPONENTIAL FACTOR, OR BY COMPLETELY ALTERING THE
MECHANISM 716 SUMMARY 717
KEY CONCEPTS 718
PROBLEMS 718
6 81 FURTHER READING
CHAPTER 16 PRINCIPLES OF ENZYME CATALYSIS A. MICHAELIS-MENTEN KINETICS
ENZYME-CATALYZED REACTIONS CAN BE DESCRIBED
AS A BINDING STEP FOLLOWED BY A CATALYTIC STEP THE MICHAELIS-MENTEN
EQUATION DESCRIBES THE KINETICS OF THE SIMPLEST ENZYME-CATALYZED
REACTIONS
THE VALUE OF THE MICHAELIS CONSTANT. KM, IS RELATED TO HOW MUCH ENZYME
HAS SUBSTRATE BOUND ENZYMES ARE CHARACTERIZED BY THEIR TURNOVER NUMBERS
AND THEIR CATALYTIC EFFICIENCIES A PERFECT ENZYME IS ONE THAT
CATALYZES THE
CHEMICAL STEP OF THE REACTION AS FAST AS THE SUBSTRATE CAN GET TO THE
ENZYME IN SOME CASES THE RELEASE OF THE PRODUCT FROM THE ENZYME AFFECTS
THE RATE OF THE REACTION THE SPECIFICITY OF ENZYMES ARISES FROM BOTH THE
RATE OF THE CHEMICAL STEP AND THE VALUE OF K M GRAPHICAL ANALYSIS OF
ENZYME KINETIC DATA
FACILITATES THE ESTIMATION OF KINETIC PARAMETERS
INHIBITORS AND MORE COMPLEX REACTION SCHEMES COMPETITIVE INHIBITORS
BLOCK THE ACTIVE SITE OF THE ENZYME IN A REVERSIBLE WAY A COMPETITIVE
INHIBITOR DOES NOT AFFECT THE MAXIMUM VELOCITY OF THE REACTION, L/ MAX ,
BUT IT
INCREASES THE MICHAELIS CONSTANT, K M REVERSIBLE NONCOMPETITIVE
INHIBITORS DECREASE
THE MAXIMUM VELOCITY, L/ MAX , WITHOUT AFFECTING THE MICHAELIS CONSTANT,
KM
588
688
689
691
693
695
696
697
699
700
7 A1
16.1
16.2
16.3
16.4
16.5
16.6
16.7
16.8
B.
16.9
16.10
704
705
16.11
720
721
721
723
725
726
729
730
732
733
735
736
736
737
740
IMAGE 12
XX DETAILED CONTENTS
16.12 SUBSTRATE-DEPENDENT NONCOMPETITIVE INHIBITORS ONLY BIND TO THE
ENZYME WHEN THE SUBSTRATE IS PRESENT 741
16.13 SOME NONCOMPETITIVE INHIBITORS ARE LINKED IRREVERSIBLY TO THE
ENZYME 742
16.14 IN A PING-PONG MECHANISM THE ENZYME BECOMES
FURTHER READING
CHAPTER 17 DIFFUSION AND TRANSPORT
785
787
787
MODIFIED TEMPORARILY DURING THE REACTION 16.15 FOR A REACTION WITH
MULTIPLE SUBSTRATES, THE ORDER OF BINDING CAN BE RANDOM OR SEQUENTIAL
16.16 ENZYMES WITH MULTIPLE BINDING SITES CAN
DISPLAY ALLOSTERIC (COOPERATIVE) BEHAVIOR 16.17 PRODUCT INHIBITION IS A
MECHANISM FOR REGULATING METABOLITE LEVELS IN CELLS
C. PROTEIN ENZYMES 16.18 ENZYMES CAN ACCELERATE REACTIONS BY LARGE
AMOUNTS 16.19 TRANSITION STATE STABILIZATION IS A MAJOR
CONTRIBUTOR TO RATE ENHANCEMENT BY ENZYMES 16.20 ENZYMES CAN ACT AS
ACIDS OR BASES TO ENHANCE REACTION RATES 16.21 PROXIMITY EFFECTS ARE
IMPORTANT FOR MANY
REACTIONS
16.22 THE SERINE PROTEASES ARE A LARGE FAMILY OF ENZYMES THAT CONTAIN A
CONSERVED SER-HIS-ASP CATALYTIC TRIAD 16.23 SIDECHAIN RECOGNITION
POSITIONS THE CATALYTIC
TRIAD NEXT TO THE PEPTIDE BOND THAT IS CLEAVED 16.24 THE SPECIFICITIES
OF SERINE PROTEASES VARY CONSIDERABLY, BUT THE CATALYTIC TRIAD IS
CONSERVED 16.25 PEPTIDE CLEAVAGE IN SERINE PROTEASES PROCEEDS
VIA A PING-PONG MECHANISM 16.26 ANGIOTENSIN-CONVERTING ENZYME IS A ZINC-
CONTAINING PROTEASE THAT IS AN IMPORTANT DRUG TARGET
16.27 CREATINE KINASE CATALYZES PHOSPHATE TRANSFER BY STABILIZING A
PLANAR PHOSPHATE INTERMEDIATE 16.28 SOME ENZYMES WORK BY POPULATING
DISFAVORED CONFORMATIONS 16.29 ANTIBODIES THAT BIND TRANSITION STATE
ANALOGS
CAN HAVE CATALYTIC ACTIVITY
D. RNA ENZYMES 16.30 SMALL SELF-CLEAVING RIBOZYMES AND RIBONUCLEASE
PROTEINS CATALYZE THE SAME REACTION 16.31 SELF-CLEAVING RIBOZYMES USE
NUCLEOTIDE BASES
FOR CATALYSIS, EVEN THOUGH THESE DO NOT HAVE P/CA VALUES WELL SUITED FOR
PROTON TRANSFER 16.32 HAIRPIN RIBOZYMES OPTIMIZE HYDROGEN BONDS TO THE
TRANSITION STATE RATHER THAN TO THE INITIAL
OR FINAL STATES
16.33 THERE ARE AT LEAST TWO POSSIBLE MECHANISMS FOR BOND CLEAVAGE BY
THE HAIRPIN RIBOZYME 16.34 THE SPLICING REACTION CATALYZED BY GROUP I
INTRONS OCCURS IN TWO STEPS 16.35 METAL IONS FACILITATE CATALYSIS BY
GROUP I INTRONS 16.36 SUBSTITUTION OF OXYGEN BY SULFUR IN RNA HELPS
IDENTIFY METALS THAT PARTICIPATE IN CATALYSIS SUMMARY KEY CONCEPTS
PROBLEMS
744
744
746
749 749
750
751
754
756
758
758
760
761
763
764
766
768 769
769
769
771
773
774 777
777 780 781 782
B.
17.11
17.12
17.13
17.14
17.15
17.16
17.17 17.18
17.19
17.20
17.21
A. RANDOM WALKS 17.1 MICROSCOPIC MOTION IS WELL DESCRIBED BY
TRAJECTORIES CALLED RANDOM WALKS 787
17.2 THE ANALYSIS OF BACTERIAL MOVEMENT IS SIMPLIFIED BY CONSIDERING
ONE-DIMENSIONAL RANDOM WALKS WITH UNIFORM STEP LENGTHS AND TIME
INTERVALS 788 17.3 THE PROBABILITY DISTRIBUTION FOR THE NUMBER OF
MOVES IN ONE DIRECTION IS GIVEN BY A GAUSSIAN FUNCTION 789
17.4 THE PROBABILITY OF MOVING A CERTAIN DISTANCE IN A ONE-DIMENSIONAL
RANDOM WALK IS ALSO GIVEN BY A GAUSSIAN FUNCTION 791
17.5 THE WIDTH OF THE DISTRIBUTION OF DISPLACEMENTS INCREASES WITH THE
SQUARE ROOT OF TIME FOR RANDOM WALKS 794
17.6 RANDOM WALKS IN TWO DIMENSIONS CAN BE ANALYZED BY COMBINING TWO
ORTHOGONAL ONE- DIMENSIONAL RANDOM WALKS 796
17.7 A TWO-DIMENSIONAL RANDOM WALK IS DESCRIBED BY TWO ONE-DIMENSIONAL
WALKS, BUT THE EFFECTIVE STEP SIZE FOR EACH IS SMALLER BY A FACTOR OF V2
798 17.8 THE ASSUMPTION OF UNIFORM STEP LENGTHS ALONG
EACH AXIS MEANS THAT THE RANDOM WALK OCCURS ON A GRID 798
17.9 A THREE-DIMENSIONAL RANDOM WALK IS DESCRIBED BY THREE ORTHOGONAL
ONE-DIMENSIONAL WALKS, AND THE EFFECTIVE STEP SIZE FOR EACH IS SMALLER
BY A FACTOR OF V3 801
17.10 THE MOVEMENT OF BACTERIA IN THE PRESENCE OF ATTRACTANTS OR
REPELLENTS IS DESCRIBED BY BIASED RANDOM WALKS 801
MACROSCOPIC DESCRIPTION OF DIFFUSION 802
FICK S FIRST LAW STATES THAT THE FLUX OF MOLECULES IS PROPORTIONAL TO
THE CONCENTRATION GRADIENT 802 FICK S SECOND LAW DESCRIBES THE RATE OF
CHANGE IN CONCENTRATION WITH TIME 804
INTEGRATION OF THE DIFFUSION EQUATION ALLOWS US TO CALCULATE THE CHANGE
IN CONCENTRATION WITH TIME 805 THE DIFFUSION CONSTANT IS RELATED TO THE
MEAN SQUARE DISPLACEMENT OF MOLECULES 807
DIFFUSION CONSTANTS DEPEND ON MOLECULAR PROPERTIES SUCH AS SIZE AND
SHAPE 809
THE DIFFUSION CONSTANT IS INVERSELY RELATED TO THE FRICTION FACTOR 810
VISCOSITY IS A MEASURE OF THE RESISTANCE TO FLOW 811 LIQUIDS WITH STRONG
INTERACTIONS BETWEEN MOLECULES HAVE HIGH VISCOSITY 812
THE STOKES-EINSTEIN EQUATION ALLOWS US TO CALCULATE THE DIFFUSION
COEFFICIENTS OF MOLECULES 812 THE DIFFUSION CONSTANTS FOR NONSPHERICAL
MOLECULES ARE ONLY SLIGHTLY DIFFERENT FROM THOSE CALCULATED
FROM THE SPHERICAL APPROXIMATION 814
DIFFUSION-LIMITED REACTION RATE CONSTANTS CAN BE CALCULATED FROM THE
DIFFUSION CONSTANTS OF MOLECULES 815
IMAGE 13
DETAILED CONTENTS XXI
17.22 ONE-DIMENSIONAL SEARCHES ON DNA INCREASE THE RATE AT WHICH
TRANSCRIPTION FACTORS FIND THEIR TARGETS 817
17.23 RESTRICTING DIFFUSION TO TWO-DIMENSIONAL MEMBRANES CAN SLOW DOWN
THE RATE OF ENCOUNTER BUT STILL SPEED UP REACTIONS 819 17.24
CONCENTRATION GRADIENTS DETERMINE THE
OUTCOMES OF MANY BIOLOGICAL PROCESSES 822 17.25 CELLS USE MOTOR PROTEINS
TO TRANSPORT CARGO OVER LONG DISTANCES AND TO SPECIFIC LOCATIONS 823
17.26 VESICLES ARE TRANSPORTED BY KINESIN MOTORS
THAT MOVE ALONG MICROTUBULE TRACKS 823
17.27 ATP HYDROLYSIS PROVIDES A POWERFUL DRIVING FORCE FOR KINESIN
MOVEMENT 825
C. EXPERIMENTAL MEASUREMENT OF DIFFUSION 826
17.28 DIFFUSION CONSTANTS CAN BE MEASURED EXPERIMENTALLY IN SEVERAL WAYS
826
17.29 MOVEMENT OF MOLECULES IN SOLUTION CAN BE DRIVEN BY CENTRIFUGAL
FORCES 827
17.30 EQUILIBRIUM CENTRIFUGATION CAN BE USED TO DETERMINE MOLECULAR
WEIGHTS 829
17.31 ELECTROPHORESIS PROVIDES AN ALTERNATIVE METHOD FOR DRIVING
MOLECULAR MOTION 830
17.32 THE ELECTROPHORETIC MOBILITY OF NUCLEIC ACIDS DECREASES WITH SIZE
831
17.33 GEL ELECTROPHORESIS ANALYSIS OF PROTEINS IS USEFUL FOR SIZE
DETERMINATION 832
SUMMARY 833
KEY CONCEPTS 834
PROBLEMS 835
FURTHER READING 836
PART VI: ASSEMBLY AND ACTIVITIY 838
CHAPTER 18 FOLDING 839
A. HOW PROTEINS FOLD 840
18.1 PROTEIN FOLDING IS GOVERNED BY THERMODYNAMICS 840 18.2 THE
REVERSIBILITY OF PROTEIN FOLDING CAN ALSO BE DEMONSTRATED BY
MANIPULATING SINGLE MOLECULES 841
18.3 UNFOLDED STATES OF PROTEINS CORRESPOND TO WIDE DISTRIBUTIONS OF
DIFFERENT CONFORMATIONS 842 18.4 PROTEIN FOLDING CANNOT BE EXPLAINED BY
AN EXHAUSTIVE SEARCH OF CONFORMATIONAL SPACE 844 18.5 MANY SMALL
PROTEINS POPULATE ONLY FULLY
UNFOLDED AND FULLY FOLDED STATES 844
18.6 THE ORDER IN WHICH SECONDARY AND TERTIARY INTERACTIONS FORM CAN
VARY IN DIFFERENT PROTEINS 845
18.7 FOLDING RATES ARE FASTER WHEN RESIDUES CLOSE IN SEQUENCE END UP
CLOSE TOGETHER IN THE FOLDED STRUCTURE 846
18.8 THE FOLDING OF SOME PROTEINS INVOLVES THE FORMATION OF TRANSIENTLY
STABLE INTERMEDIATES 847 18.9 FOLDING PATHWAYS CAN HAVE MULTIPLE
INTERMEDIATES 850
18.10 CHANGES IN THE SEQUENCE OF A PROTEIN AT CERTAIN POSITIONS CAN
AFFECT FOLDING RATES SUBSTANTIALLY 850 18.11 THE NATURE OF THE
TRANSITION STATE CAN BE IDENTIFIED BY MAPPING THE EFFECT OF MUTATIONS
ON THE FOLDING AND UNFOLDING RATES 852
18.12 THE PROCESS OF PROTEIN FOLDING CAN BE DESCRIBED AS FUNNELED
MOVEMENT ON A MULTIDIMENSIONAL FREE-ENERGY LANDSCAPE 856
B. CHAPERONES FOR PROTEIN FOLDING 857 18.13 MANY PROTEINS TEND TO
AGGREGATE RATHER THAN FOLD 857
18.14 THE HIGH CONCENTRATION OF MACROMOLECULES INSIDE THE CELL MAKES THE
PROBLEM OF AGGREGATION PARTICULARLY ACUTE 858
18.15 PROTEINS INSIDE THE CELL USUALLY FOLD INTO A FUNCTIONAL FORM
RAPIDLY 860
18.16 SOME PROTEINS FORM IRREVERSIBLE AGGREGATES THAT ARE TOXIC TO CELLS
861
18.17 MOLECULAR CHAPERONES ARE PROTEINS THAT PREVENT PROTEIN AGGREGATION
863
18.18 HSP70 RECOGNIZES SHORT PEPTIDES WITH SEQUENCES THAT ARE
CHARACTERISTIC OF THE INTERIOR SEGMENTS OF PROTEINS 866
18.19 HSP70 BINDS AND RELEASES PROTEIN CHAINS IN A CYCLE THAT IS COUPLED
TO ATP BINDING AND HYDROLYSIS 866
18.20 THE GROEL CHAPERONIN FORMS A HOLLOW DOUBLE-RING STRUCTURE WITHIN
WHICH PROTEIN MOLECULES CAN FOLD 868
18.21 GROEL WORKS LIKE A TWO-STROKE ENGINE, BINDING AND RELEASING
PROTEINS 870
18.22 GROEL-GROES CAN ACCELERATE THE FOLDING OF PROTEINS THROUGH PASSIVE
AND ACTIVE MECHANISMS 872
C. RNA FOLDING 872
18.23 THE ELECTROSTATIC FIELD AROUND RNA LEADS TO THE DIFFUSE
LOCALIZATION OF METAL IONS 873
18.24 RNA FOLDING CAN BE DRIVEN BY INCREASING THE CONCENTRATION OF METAL
IONS 874
18.25 RNAS FORM STABLE SECONDARY STRUCTURAL ELEMENTS, WHICH INCREASES
THEIR TENDENCY TO MISFOLD 875
18.26 RNA FOLDING IS HIERARCHICAL WITH MULTIPLE STABLE INTERMEDIATES 877
18.27 COLLAPSE IS AN EARLY EVENT IN THE FOLDING OF RNA 878 18.28 RNA
FOLDING LANDSCAPES ARE HIGHLY RUGGED 880 SUMMARY 882
KEY CONCEPTS 883
PROBLEMS 884
FURTHER READING 886
CHAPTER 19 FIDELITY IN DNA AND PROTEIN SYNTHESIS 887
A. MEASURING THE STABILITY OF DNA DUPLEXES 19.1 THE DIFFERENCE IN FREE
ENERGY BETWEEN MATCHED AND MISMATCHED BASE PAIRS CAN BE DETERMINED
BY MEASURING THE MELTING TEMPERATURE OF DNA
IMAGE 14
XXII DETAILED CONTENTS
19.2
19.3
19.4
19.5
19.6
19.7
B.
19.8 19.9
19.10
19.11 19.12
19.13
19.14
19.15
19.16
19.17
19.18
DNA MELTING CAN BE STUDIED BY UV ABSORPTION SPECTROSCOPY 889
THE CHANGES IN ENTHALPY AND ENTROPY ASSOCIATED WITH DNA MELTING CAN BE
DETERMINED FROM THE CONCENTRATION DEPENDENCE OF MELTING CURVES 890 DNA
DUPLEXES CONTAINING A MISMATCHED BASE
PAIR AT ONE END ARE ONLY MARGINALLY LESS STABLE THAN DUPLEXES WITH
MATCHED BASES 892
THE ENTROPY OF EACH DNA CHAIN IS REDUCED UPON FORMING A DUPLEX 894
THE STABILITY OF DNA DEPENDS ON THE PATTERN ON BASE STACKS IN THE DUPLEX
895
BASE STACKING IS MORE IMPORTANT THAN HYDROGEN BONDING IN DETERMINING THE
STABILITY OF DNA HELICES
FIDELITY IN DNA REPLICATION THE PROCESS OF DNA REPLICATION IS VERY
ACCURATE THE ENERGY OF DNA BASE-PAIRING CANNOT EXPLAIN THE ACCURACY OF
DNA REPLICATION THE OVERALL PROCESS OF DNA SYNTHESIS CAN BE
DESCRIBED AS A SERIES OF KINETIC STEPS PRIMER ELONGATION BY POLYMERASE
IS QUITE RAPID THE RATE-LIMITING STEP IN THE DNA SYNTHESIS REACTION IS A
CONFORMATIONAL CHANGE IN DNA
POLYMERASE DETERMINATION OF THE VALUES OF V MAX AND K M FOR THE
INCORPORATION OF CORRECT AND INCORRECT
BASE PAIRS PROVIDES INSIGHTS INTO FIDELITY DNA POLYMERASE HAS A NUCLEASE
ACTIVITY THAT CAN REMOVE BASES FROM THE 3 END OF A DNA STRAND THE
STRUCTURE OF DNA POLYMERASE HAS FINGERS, PALM, AND THUMB SUBDOMAINS DNA
POLYMERASE BINDS DNA USING THE PALM AND NEARLY ENCIRCLES IT THE ACTIVE
SITE OF POLYMERASE CONTAINS TWO METALS IONS THAT CATALYZE NUCLEOTIDE
ADDITION A CONFORMATIONAL CHANGE IN DNA POLYMERASE UPON BINDING DNTP
CONTRIBUTES TO REPLICATION FIDELITY
897
898
898
900
902 904
905
907
908
909
910
911
19.19 DNA POLYMERASES RECOGNIZE DNA USING THE BACKBONE AND MINOR GROOVE
19.20 DNA POLYMERASES SENSE THE SHAPES OF CORRECTLY PAIRED BASES 19.21
THE SHAPE OF A NUCLEOTIDE IS MORE IMPORTANT
FOR ITS BEING INCORPORATED INTO DNA THAN ITS ABILITY TO FORM HYDROGEN
BONDS 19.22 THE GROWING DNA STRAND CAN SHUTTLE BETWEEN THE POLYMERASE
AND EXONUCLEASE ACTIVE SITES
C. HOW RIBOSOMES ACHIEVE FIDELITY 19.23 THE RIBOSOME HAS TWO SUBUNITS,
EACH OF WHICH IS A LARGE COMPLEX OF RNA AND PROTEINS 19.24 PROTEIN
SYNTHESIS ON THE RIBOSOME OCCURS
AS A REPEATED SERIES OF STEPS OF TRNA AND PROTEIN BINDING, WITH
CONFORMATIONAL CHANGES IN THE RIBOSOME 19.25 SELECTION OF THE CORRECT
A-SITE TRNA BY
BASE-PAIRING ALONE CANNOT EXPLAIN RIBOSOME FIDELITY 19.26 A
RIBOSOME-INDUCED BEND IN THE EF-TUTRNA COMPLEX PLAYS AN IMPORTANT ROLE
IN GENERATING
SPECIFICITY
19.27 THE RIBOSOME UNDERGOES CONFORMATIONAL CHANGES DURING THE PROCESS
OF TRNA SELECTION 19.28 TIGHT INTERACTIONS IN THE DECODING CENTER CAN
ONLY OCCUR FOR CORRECT CODON-ANTICODON
PAIRS
19.29 COUPLING OF THE DECODING CENTER AND THE GTPASE ACTIVE SITE OF
EF-TU INVOLVES MULTIPLE CONFORMATIONAL REARRANGEMENTS
19.30 THE ACTIVE SITE OF EF-TU NEEDS ONLY A SMALL REARRANGEMENT TO BE
ACTIVATED 19.31 RELEASE OF EF-TU ALLOWS THE AMINOACYL GROUP OF THE
A-SITE TRNA TO MOVE TO THE
PEPTIDYL TRANSFER CENTER 19.32 THE RIBOSOME CATALYZES PEPTIDYL TRANSFER
SUMMARY KEY CONCEPTS
PROBLEMS
913 FURTHER READING
915
917
918
919
920
921
921
923
924
925
926
929
930
931 932 934 935
936 937
|
| any_adam_object | 1 |
| author | Lehninger, Albert L. 1917-1986 |
| author_GND | (DE-588)132539519 |
| author_facet | Lehninger, Albert L. 1917-1986 |
| author_role | aut |
| author_sort | Lehninger, Albert L. 1917-1986 |
| author_variant | a l l al all |
| building | Verbundindex |
| bvnumber | BV008070512 |
| classification_rvk | WD 4000 WD 4010 |
| ctrlnum | (OCoLC)254156782 (DE-599)BVBBV008070512 |
| discipline | Biologie |
| edition | 2. ed., 2. print. |
| format | Book |
| fullrecord | <?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01844nam a2200445 c 4500</leader><controlfield tag="001">BV008070512</controlfield><controlfield tag="003">DE-604</controlfield><controlfield tag="005">20141205 </controlfield><controlfield tag="007">t</controlfield><controlfield tag="008">930712s1976 ad|| |||| 00||| eng d</controlfield><datafield tag="020" ind1=" " ind2=" "><subfield code="a">0879010479</subfield><subfield code="9">0-87901-047-9</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(OCoLC)254156782</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)BVBBV008070512</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-604</subfield><subfield code="b">ger</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1="0" ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="049" ind1=" " ind2=" "><subfield code="a">DE-19</subfield><subfield code="a">DE-188</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">WD 4000</subfield><subfield code="0">(DE-625)148175:</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="084" ind1=" " ind2=" "><subfield code="a">WD 4010</subfield><subfield code="0">(DE-625)148176:</subfield><subfield code="2">rvk</subfield></datafield><datafield tag="100" ind1="1" ind2=" "><subfield code="a">Lehninger, Albert L.</subfield><subfield code="d">1917-1986</subfield><subfield code="e">Verfasser</subfield><subfield code="0">(DE-588)132539519</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Biochemistry</subfield><subfield code="b">the molecular basis of cell structure and function</subfield><subfield code="c">Albert L. Lehninger</subfield></datafield><datafield tag="250" ind1=" " ind2=" "><subfield code="a">2. ed., 2. print.</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="a">New York</subfield><subfield code="b">Worth</subfield><subfield code="c">1976</subfield></datafield><datafield tag="300" ind1=" " ind2=" "><subfield code="a">XXIII, 1104 S.</subfield><subfield code="b">Ill., graph. Darst.</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="b">n</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="b">nc</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Zelle</subfield><subfield code="0">(DE-588)4067537-3</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Biochemie</subfield><subfield code="0">(DE-588)4006777-4</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="650" ind1="0" ind2="7"><subfield code="a">Funktion</subfield><subfield code="0">(DE-588)4195664-3</subfield><subfield code="2">gnd</subfield><subfield code="9">rswk-swf</subfield></datafield><datafield tag="655" ind1=" " ind2="7"><subfield code="8">1\p</subfield><subfield code="0">(DE-588)4123623-3</subfield><subfield code="a">Lehrbuch</subfield><subfield code="2">gnd-content</subfield></datafield><datafield tag="689" ind1="0" ind2="0"><subfield code="a">Zelle</subfield><subfield code="0">(DE-588)4067537-3</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2="1"><subfield code="a">Funktion</subfield><subfield code="0">(DE-588)4195664-3</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="0" ind2=" "><subfield code="8">2\p</subfield><subfield code="5">DE-604</subfield></datafield><datafield tag="689" ind1="1" ind2="0"><subfield code="a">Biochemie</subfield><subfield code="0">(DE-588)4006777-4</subfield><subfield code="D">s</subfield></datafield><datafield tag="689" ind1="1" ind2=" "><subfield code="8">3\p</subfield><subfield code="5">DE-604</subfield></datafield><datafield tag="856" ind1="4" ind2="2"><subfield code="m">SWB Datenaustausch</subfield><subfield code="q">application/pdf</subfield><subfield code="u">http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005311927&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA</subfield><subfield code="3">Inhaltsverzeichnis</subfield></datafield><datafield tag="999" ind1=" " ind2=" "><subfield code="a">oai:aleph.bib-bvb.de:BVB01-005311927</subfield></datafield><datafield tag="883" ind1="1" ind2=" "><subfield code="8">1\p</subfield><subfield code="a">cgwrk</subfield><subfield code="d">20201028</subfield><subfield code="q">DE-101</subfield><subfield code="u">https://d-nb.info/provenance/plan#cgwrk</subfield></datafield><datafield tag="883" ind1="1" ind2=" "><subfield code="8">2\p</subfield><subfield code="a">cgwrk</subfield><subfield code="d">20201028</subfield><subfield code="q">DE-101</subfield><subfield code="u">https://d-nb.info/provenance/plan#cgwrk</subfield></datafield><datafield tag="883" ind1="1" ind2=" "><subfield code="8">3\p</subfield><subfield code="a">cgwrk</subfield><subfield code="d">20201028</subfield><subfield code="q">DE-101</subfield><subfield code="u">https://d-nb.info/provenance/plan#cgwrk</subfield></datafield></record></collection> |
| genre | 1\p (DE-588)4123623-3 Lehrbuch gnd-content |
| genre_facet | Lehrbuch |
| id | DE-604.BV008070512 |
| illustrated | Illustrated |
| indexdate | 2024-07-09T17:13:52Z |
| institution | BVB |
| isbn | 0879010479 |
| language | English |
| oai_aleph_id | oai:aleph.bib-bvb.de:BVB01-005311927 |
| oclc_num | 254156782 |
| open_access_boolean | |
| owner | DE-19 DE-BY-UBM DE-188 |
| owner_facet | DE-19 DE-BY-UBM DE-188 |
| physical | XXIII, 1104 S. Ill., graph. Darst. |
| publishDate | 1976 |
| publishDateSearch | 1976 |
| publishDateSort | 1976 |
| publisher | Worth |
| record_format | marc |
| spelling | Lehninger, Albert L. 1917-1986 Verfasser (DE-588)132539519 aut Biochemistry the molecular basis of cell structure and function Albert L. Lehninger 2. ed., 2. print. New York Worth 1976 XXIII, 1104 S. Ill., graph. Darst. txt rdacontent n rdamedia nc rdacarrier Zelle (DE-588)4067537-3 gnd rswk-swf Biochemie (DE-588)4006777-4 gnd rswk-swf Funktion (DE-588)4195664-3 gnd rswk-swf 1\p (DE-588)4123623-3 Lehrbuch gnd-content Zelle (DE-588)4067537-3 s Funktion (DE-588)4195664-3 s 2\p DE-604 Biochemie (DE-588)4006777-4 s 3\p DE-604 SWB Datenaustausch application/pdf http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005311927&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA Inhaltsverzeichnis 1\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 2\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk 3\p cgwrk 20201028 DE-101 https://d-nb.info/provenance/plan#cgwrk |
| spellingShingle | Lehninger, Albert L. 1917-1986 Biochemistry the molecular basis of cell structure and function Zelle (DE-588)4067537-3 gnd Biochemie (DE-588)4006777-4 gnd Funktion (DE-588)4195664-3 gnd |
| subject_GND | (DE-588)4067537-3 (DE-588)4006777-4 (DE-588)4195664-3 (DE-588)4123623-3 |
| title | Biochemistry the molecular basis of cell structure and function |
| title_auth | Biochemistry the molecular basis of cell structure and function |
| title_exact_search | Biochemistry the molecular basis of cell structure and function |
| title_full | Biochemistry the molecular basis of cell structure and function Albert L. Lehninger |
| title_fullStr | Biochemistry the molecular basis of cell structure and function Albert L. Lehninger |
| title_full_unstemmed | Biochemistry the molecular basis of cell structure and function Albert L. Lehninger |
| title_short | Biochemistry |
| title_sort | biochemistry the molecular basis of cell structure and function |
| title_sub | the molecular basis of cell structure and function |
| topic | Zelle (DE-588)4067537-3 gnd Biochemie (DE-588)4006777-4 gnd Funktion (DE-588)4195664-3 gnd |
| topic_facet | Zelle Biochemie Funktion Lehrbuch |
| url | http://bvbr.bib-bvb.de:8991/F?func=service&doc_library=BVB01&local_base=BVB01&doc_number=005311927&sequence=000001&line_number=0001&func_code=DB_RECORDS&service_type=MEDIA |
| work_keys_str_mv | AT lehningeralbertl biochemistrythemolecularbasisofcellstructureandfunction |