Biochemistry

Half Title
Title Page
Copyright Page
Dedication
Table of Contents
Preface
	Considering Metabolism
	Brevity
	Organization
	Key Features
Preface
Acknowledgments
Author
A
B
c
D
E
F
G
H
I
K
L
M
N
O
P
Q
R
s
T
u
v
w
x
Y
z
1 Foundations
	1.1 Origins of Biochemistry
	1.2 Some Chemical Ideas
		1.2.1 Reactions and Their Kinetic Description
			1.2.1.1 Equilibrium
		1.2.2 The Steady-State
	1.3 Acid–Base Reactions
	1.4 Redox
	1.5 Energy
	1.6 Cell Theory
	1.7 Species Hierarchy and Evolution
	1.8 Biological Systems
	Key Terms
	Bibliography
2 Water
	2.1 Structure of Water
		2.1.1 Gas Phase Water
		2.1.2 Partial Charges and Electronegativity
		2.1.3 Condensed Phase Water: Hydrogen Bonding
		2.1.4 Hydrogen Bonding in Condensed Phase Water
	2.2 The Hydrophobic Effect
	2.3 Molecules Soluble in Water
	2.4 High Heat Retention: The Unusual Specific Heat of Liquid Water
	2.5 Ionization of Water
	2.6 Some Definitions for the Study of Acids and Bases
	2.7 The pH Scale
	2.8 The Henderson–Hasselbalch Equation
	2.9 Titration and Buffering
	Summary
	Review Questions
	Chapter 2 Addendum: The Dielectric
	Key Terms
	Bibliography
3 Lipids
	3.1 Significance
	3.2 Fatty Acids
	3.3 Triacylglycerols
	3.4 Phospholipids
	3.5 Cholesterol
	3.6 Lipid–Water Interactions of Amphipathic Molecules
	3.7 Phospholipid Monolayers
	3.8 Lipid Composition of Membranes
	3.9 Water Permeability of Membranes and Osmosis
	Summary
	Review Questions
	Chapter 3 Addendum: Inverted Micelles
	Key Terms
	Bibliography
4 Carbohydrates
	4.1 Monosaccharides
	4.2 Ring Formation in Sugars
	4.3 Disaccharides
	4.4 Polysaccharides
		4.4.1 Linear Polysaccharides
		4.4.2 Branched Polysaccharides
	4.5 Carbohydrate Derivatives
		4.5.1 Simple Modifications
		4.5.2 Substituted Carbohydrates
	Summary
	Review Questions
	Chapter 4 Addendum: The Discovery of Stereoisomerism
	Key Terms
	Bibliography
5 Amino Acids and Proteins
	5.1 Common Structure of the Amino Acids
	5.2 Biology of the Amino Acids
	5.3 Amino Acid Individuality: The R Groups
		5.3.1 Polarities
		5.3.2 Functional Groups
	5.4 Acid–Base Properties and Charge
		5.4.1 Titration and Net Charge
		5.4.2 Interactions between the α-Carboxylate and α-Amine Groups
			5.4.2.1 Inductive Effect
			5.4.2.2 Electric Field Effect
		5.4.3 Multiple Dissociable Groups
	5.5 The Peptide Bond
	5.6 Peptides and Proteins
	5.7 Levels of Protein Structure
		5.7.1 Primary Structure
		5.7.2 Secondary Structure
			5.7.2.1 α-Helix
			5.7.2.2 β-Sheet
		5.7.3 Domains
		5.7.4 Tertiary Structure
		5.7.5 Quaternary Structure
	5.8 Protein Folding
	5.9 Oxygen Binding in Myoglobin and Hemoglobin
	5.10 Other Binding Reactions Involving Proteins
		5.10.1 Extracellular Binding Proteins
		5.10.2 Cell Surface Binding Proteins
		5.10.3 Intracellular Binding Proteins
	5.11 Protein Purification and Analysis
		5.11.1 Purification
		5.11.2 Analysis
	Summary
	Review Questions
	Chapter 5 Addendum: Atomic Charged Forms
	Key Terms
	Bibliography
6 Enzymes
	6.1 Energetics of Enzyme-Catalyzed Reactions
	6.2 The Enzyme Assay and Initial Velocity
	6.3 A Simple Kinetic Mechanism
		6.3.1 Assumptions
		6.3.2 The Michaelis–Menten Equation
	6.4 How the Michaelis–Menten Equation Describes Enzyme Behavior
	6.5 The Meaning of Km
	6.6 Reversible Inhibition
		6.6.1 Competitive Inhibition
		6.6.2 Anticompetitive Inhibition (Uncompetitive)
		6.6.3 Mixed Inhibition (Noncompetitive)
	6.7 Double-Reciprocal or Lineweaver–Burk Plot
	6.8 Allosteric Enzymes
	6.9 Irreversible Inhibition
	6.10 Enzyme Mechanisms
		6.10.1 Nucleophilic Substitution
		6.10.2 Acid–Base Catalysis
	6.11 Enzyme Categories
	6.12 Enzyme-Like Qualities of Membrane Transport Proteins
	Summary
	Review Questions
	Chapter 6 Addendum: The Haldane Relationship
	Key Terms
	Bibliography
7 Coenzymes
	7.1 Coenzymes: Bound and Mobile
	7.2 Coenzymes and Vitamins
	7.3 Redox Coenzymes
		7.3.1 Nicotinamides
		7.3.2 Ubiquinone
		7.3.3 Flavin Coenzymes
	7.4 Acyl Transfers
		7.4.1 CoA
		7.4.2 Carnitine
		7.4.3 Lipoic Acid
	7.5 Carboxylation
		7.5.1 Biotin
		7.5.2 Vitamin K
	7.6 Exchange Coenzymes
		7.6.1 Thiamine Pyrophosphate
		7.6.2 Pyridoxal Phosphate
	7.7 Metal Ion Cofactors
		7.7.1 Mg2+
		7.7.2 Iron
		7.7.3 Copper
		7.7.4 Co2+
		7.7.5 Mn2+and Zn2+
		7.7.6 Selenium
		7.7.7 Dietary Essentials
	Review Questions
	Chapter 7 Addendum: The Vitamin K Cycle
	Key Terms
	Bibliography
8 Metabolism and Energy
	8.1 Origins of Thermodynamics
	8.2 First Law of Thermodynamics
		8.2.1 Heat and Work
		8.2.2 Enthalpy
	8.3 Entropy and the Second Law of Thermodynamics
		8.3.1 Entropy as a Ratio of Heat to Temperature
		8.3.2 Entropy as a Statistical Distribution of States
	8.4 Free Energy
	8.5 Standard Free Energy
	8.6 Nonstandard Free Energy Changes
	8.7 Near-Equilibrium and Metabolically Irreversible Reactions
	8.8 ATP
	8.9 Energy Coupling with ATP
		8.9.1 Creatine Phosphokinase
		8.9.2 NDP Kinase
		8.9.3 Adenylate Kinase
	8.10 Energy of Redox Reactions
		8.10.1 Electricity Fundamentals
		8.10.2 The Electrochemical Cell
		8.10.3 Standard Reduction Potentials
		8.10.4 Reduction Potentials and Free Energy
		8.10.5 Reduction Potentials
	8.11 Mobile Cofactors and the Pathway View
	Summary
	Review Questions
	Chapter 8 Addendum: Free Energy Derivation
	Key Terms
	Bibliography
9 Glycolysis
	9.1 Glucose Transport
	9.2 From Glucose to Pyruvate
		9.2.1 Hexokinase
		9.2.2 Glucose Phosphate Isomerase
		9.2.3 Phosphofructokinase
		9.2.4 Aldolase
		9.2.5 Triose Phosphate Isomerase
		9.2.6 Glyceraldehyde Phosphate Dehydrogenase
		9.2.7 Phosphoglycerate Kinase
		9.2.8 Phosphoglycerate Mutase
		9.2.9 Enolase
		9.2.10 Pyruvate Kinase
	9.3 Completing the Pathway
		9.3.1 Lactate Formation
		9.3.2 Ethanol Formation
	9.4 Energetics of Glycolysis
		9.4.1 Pathway Thermodynamics
		9.4.2 Red Blood Cell Shunt Pathway
		9.4.3 Arsenate Poisoning
		9.4.4 Fructose Metabolism
		9.4.5 Energy Balance and Glycolytic Connections
	9.5 Metabolic Connections to Glycolysis
		9.5.1 Alternative Entry Points
		9.5.2 Glycolytic Intermediates as Intersection Points
		9.5.3 Alternative Endpoints of Glycolysis
	Summary
	Review Questions
	Chapter 9 Addendum: Alternatives to Glycolysis
	Key Terms
	Bibliography
10 The Krebs Cycle
	10.1 A Cyclic Pathway
	10.2 Acetyl-CoA: Substrate of the Krebs Cycle
	10.3 Overview of Carbon Flow
	10.4 Steps of the Pathway
		10.4.1 Citrate Synthase
		10.4.2 Aconitase
		10.4.3 Cis-Aconitate as a Krebs Cycle Intermediate
		10.4.4 Prochirality
		10.4.5 The R/S System of Nomenclature
		10.4.6 Fluoroacetate Poisoning
		10.4.7 Isocitrate DH
		10.4.8 α-Ketoglutarate DH Complex
		10.4.9 Succinyl-CoA Synthetase
		10.4.10 Succinate DH
		10.4.11 Fumarase
		10.4.12 Malate DH
	10.5 Energy Balance
	10.6 Regulation
	10.7 Krebs Cycle as a Second Crossroad of Metabolic Pathways
	Summary
	Review Questions
	Chapter 10 Addendum: Cyclic Pathways Connected to the Krebs Cycle
		1. Glyoxylate Cycle
		2. Itaconate Pathway
	Key Terms
	Bibliography
11 Oxidative Phosphorylation
	11.1 The Phenomenon
	11.2 Mitochondrial Inner Membrane
	11.3 Carriers of Electrons, Protons, or Both
		11.3.1 Carriers of Electrons
		11.3.2 Carriers of Protons
		11.3.3 Carriers of Both Electrons and Protons
	11.4 Membrane-Bound Complexes
	11.5 The Electrochemical Cell and the Mitochondria
	11.6 Electron Pathways
		11.6.1 Sequence of Electron Flow
		11.6.2 Energetics of Electron Flow
	11.7 Mechanisms of the Mitochondrial Membrane Protein Complexes
		11.7.1 Complex I: Proton Pump
		11.7.2 Complex II: Succinate Dehydrogenase
		11.7.3 Complex III: Loop Mechanism
		11.7.4 Complex IV: Pump and Annihilation
		11.7.5 Complex V: ATP Synthesis
			11.7.5.1 The Stator
			11.7.5.2 The Rotor
	11.8 Proton-Motive Force
		11.8.1 Electric Circuit Analogy to the Proton Gradient
		11.8.2 Utilization of Δp beyond ATP Synthesis
	11.9 Mitochondrial Membrane Transport
		11.9.1 Adenine Nucleotide Translocase
		11.9.2 Phosphate Exchange
		11.9.3 Other Transport Proteins
		11.9.4 Coupling of Oxidation and Phosphorylation
	11.10 Uncoupling
		11.10.1 Physiological Uncoupling: Brown Fat
	11.11 Superoxide Formation by Mitochondria
	11.12 Control of Mitochondria
	11.13 How Mitochondria Can Utilize Cytosolic NADH
		11.13.1 Glycerol Phosphate Shuttle
		11.13.2 Malate/Aspartate Shuttle
	Summary
	Review Questions
	Chapter 11 Addendum: Supercomplexes
	Key Terms
	Bibliography
12 Photosynthesis
	12.1 Light and Carbon Reactions
	12.2 Chloroplasts
		12.2.1 Orientations: N and P Sides of the Membrane
		12.2.2 Light Reactions of Photosynthesis as a Reversed Oxidative Phosphorylation
		12.2.3 Carbon Reactions of Photosynthesis: CO2 Fixation
	12.3 Harnessing Light Energy
		12.3.1 Light Absorption and the Antennae
		12.3.2 Electron Transfer at Reaction Centers
	12.4 Proton and Electron Flow for the Light Reactions
	12.5 Cyclic Electron Transfer and Other Variations
	12.6 The Calvin Cycle
		12.6.1 Ribulose Bisphosphate Carboxylase
		12.6.2 Reaction Steps Following Carbon Fixation to Glyceraldehyde-P: Energy Consuming Portion
		12.6.3 From GAP to the RuBP: Overview
		12.6.4 From GAP to the RuBisCo Step: Reactions
	12.7 Variations in CO2 Handling: C3, C4, and CAM Plants
	12.8 Pathway Endpoints: Sucrose and Starch
	Summary
	Review Questions
	Chapter 12 Addendum: Dark vs Carbon Reactions
	Key Terms
	Bibliography
13 Carbohydrate Pathways Related to Glycolysis
	13.1 Glycogen Metabolism
		13.1.1 Glycogen Synthesis
		13.1.2 Glycogenolysis
		13.1.3 Physiological Context of Glycogen Metabolism
		13.1.4 Regulation of Glycogen Metabolism by Glucagon
		13.1.5 Regulation of Glycogen Metabolism by Epinephrine
		13.1.6 Regulation of Glycogen Metabolism by Insulin
		13.1.7 Regulation of Glycogen Metabolism by AMP Kinase
	13.2 Gluconeogenesis
		13.2.1 Lactate Dehydrogenase as a Gluconeogenic Enzyme
		13.2.2 Pyruvate to PEP
		13.2.3 Indirect Transport of Oxaloacetate from Mitochondria to Cytosol
		13.2.4 Fructose-1,6-P2 to Fructose-6-P
		13.2.5 Glucose-6-P to Glucose
		13.2.6 Pathway Integration: Glycolysis, Glycogen Metabolism, and Gluconeogenesis
			13.2.6.1 The Feeding–Fasting Transition
			13.2.6.2 The Resting–Exercise Transition
	13.3 The Pentose Phosphate Shunt
		13.3.1 Oxidative Stage
		13.3.2 Nonoxidative Stage
			13.3.2.1 Reactions of the Nonoxidative Stage
			13.3.2.2 A Pseudo Three-Dimensional View and Comparison to the Calvin Cycle
		13.3.3 Distribution Between NADPH Production and Ribose-5-P
	13.4 Galactose Utilization
	Summary
	Review Questions
	Chapter 13 Addendum: Phosphorylation of Glycogen
	Key Terms
	Bibliography
14 Lipid Metabolism
	14.1 Absorption of Dietary Lipids
	14.2 Fatty Acid Oxidation
		14.2.1 Activation
		14.2.2 Transport
		14.2.3 β-Oxidation
			14.2.3.1 Unsaturated Fatty Acids
			14.2.3.2 Odd Carbon-Numbered Fatty Acids
			14.2.3.3 Shorter and Longer Fatty Acids
	14.3 Ketone Body Metabolism
	14.4 Fatty Acid Biosynthesis
		14.4.1 Export of Acetyl-CoA to the Cytosol
		14.4.2 Carboxylation of Acetyl-CoA to Malonyl-CoA
		14.4.3 Sequential Addition of Two-Carbon Fragments to Form Palmitate
			14.4.3.1 Loading
			14.4.3.2 Condensation
			14.4.3.3 Reduction
			14.4.3.4 Dehydration
			14.4.3.5 Second Reduction
	14.5 Triacylglycerol Formation
	14.6 Phospholipid Metabolism
	14.7 Cholesterol Metabolism
	14.8 Other Lipids
		14.8.1 Eicosanoids
		14.8.2 Sphingolipids
		14.8.3 Unusual Bacterial Fatty Acids
	14.9 Overview of Lipid Metabolism in the Fed and Fasted States
	14.10 Integration of Lipid and Carbohydrate Metabolism
		14.10.1 Lipid and Carbohydrate Intersections in the Feeding–Fasting Transition
		14.10.2 Lipid and Carbohydrate Intersections in the Resting–Exercise Transition
		14.10.3 Lipid and Carbohydrate Intersections in Diabetes Mellitus
	Summary
	Review Questions
	Chapter 14 Addendum: The Isoprenes
	Key Terms
	Bibliography
15 Nitrogen Metabolism
	15.1 The Nitrogen Cycle
	15.2 Reaction Types in NH3 Assimilation
		15.2.1 Redox-Neutral
		15.2.2 Redox-Active
		15.2.3 Redox-Balanced
	15.3 Metabolically Irreversible Nitrogen Exchange Reactions
	15.4 Near-Equilibrium Nitrogen Exchange Reactions
		15.4.1 Glutamate DH
		15.4.2 Transaminases
	15.5 The Urea Cycle
		15.5.1 [NH3] Exceeds [Aspartate]
		15.5.2 [Aspartate] Exceeds [NH3]
		15.5.3 Steps from NH3 to Citrulline
		15.5.4 Cytosolic Steps of the Urea Cycle
		15.5.5 Overall Urea Cycle
	15.6 Amino Acid Metabolism: Catabolism
		15.6.1 Branched-Chain Amino Acid Breakdown
		15.6.2 Threonine
		15.6.3 Lysine
		15.6.4 Tryptophan
		15.6.5 Phenylalanine and Tyrosine Degradation
		15.6.6 Amino Acids Directly Connected to Major Metabolic Pathways
		15.6.7 Arginine, Proline, and Histidine Are All Converted to Glutamate
		15.6.8 One-Carbon (1C) Metabolism and Serine, Glycine, and Methionine Breakdown
	15.7 Amino Acids: Anabolism
		15.7.1 Nonessential Amino Acids
		15.7.2 Essential Amino Acids
		15.7.3 Aromatic Amino Acid Biosynthesis
	15.8 Nucleotide Metabolism
		15.8.1 Pyrimidine Synthesis
		15.8.2 Pyrimidine Degradation
		15.8.3 Purine Synthesis
		15.8.4 Purine Degradation
		15.8.5 Salvage Reactions
		15.8.6 Purine Nucleotide Regulation
		15.8.7 Purine Nucleotide Cycle
		15.8.8 Deoxynucleotide Formation
		15.8.9 A Unique Methylation to Form dTMP
	15.9 Other Nitrogen Pathways
	Summary
	Review Questions
	Chapter 15 Addendum: Nitrogen Disposal
		The Tilapia of Lake Magadi
		The Alligator and the Crocodile
		Low Creatinine and Liver Failure
	Key Terms
	References
16 Nucleic Acids
	16.1 Strand Structures of the Nucleic Acids
	16.2 Structure of the Double Helix
	16.3 Supercoiling
	16.4 Histones
	16.5 Replication
		16.5.1 Initiation
		16.5.2 Replication Fork and the Replisome
		16.5.3 Primer Formation
		16.5.4 Creating the Double Helix
		16.5.5 Distinctive Features of Eukaryotic Replication
	16.6 DNA Repair
		16.6.1 Mismatch Repair
		16.6.2 Excision Repair
		16.6.3 PARP
	16.7 Transcription
		16.7.1 RNA Polymerase Binding to DNA
		16.7.2 Transcription Events in E. coli
		16.7.3 Eukaryotic Transcription
	Summary
	Review Questions
	Chapter 16 Addendum: Restriction Enzymes and PCR
		Restriction Enzymes
		PCR
	Key Terms
	Bibliography
17 Protein Synthesis and Degradation
	17.1 Three Forms of RNA Employed in Protein Synthesis
		17.1.1 tRNA
		17.1.2 rRNA and the Ribosomes
	17.2 The Genetic Code
	17.3 Steps in Protein Synthesis
		17.3.1 Initiation
		17.3.2 Elongation
		17.3.3 Termination
		17.3.4 Distinctive Features of Eukaryotic Translation
		17.3.5 Regulation of Eukaryotic Translation
	17.4 Co-Translational and Post-Translational Modifications of Proteins
		17.4.1 Co-Translational Modifications
		17.4.2 Post-Translational Modifications
	17.5 Protein Degradation
		17.5.1 Extracellular Proteases
		17.5.2 Intracellular Proteases
	17.6 The mTOR Pathway in the Control of Protein Synthesis
	Summary
	Review Questions
	Chapter 17 Addendum: Skeletal Muscle and Exercise
	Key Terms
	Bibliography
Appendix
	A1. Mathematical Ideas
		A1.1 Vectors
		A1.2 Logarithms
		A1.3 Geometric Mean
	A2. Chemical Fundamentals
		A2.1 Curved Arrow Conventions
	A3. Derivation of the General Free Energy Equation
	A4. Lipids
		A4.1 Fatty Acids
		A4.2 Phospholipids
	A5. Derivation of Equations for Reversible Enzyme Inhibition
		A5.1 Competitive Inhibition
		A5.2 Anticompetitive (Uncompetitive) Inhibition
		A5.3 Mixed (Noncompetitive) Inhibition
	A6. The Lipid-Water Interface
Index