Author Fromm, Herbert J.

Title Essentials of biochemistry / Herbert J. Fromm, Mark S. Hargrove.

Pub Info Berlin ; New York : Springer, [2012] ©2012

Table of Contents
1.	The Cell and Its Components					1
1.1.	Typical Prokaryotic Cell: Escherichia coli					1
1.2.	Archaea					2
1.3.	Eukaryotic Cell (Non-Plant)					3
1.4.	Eukaryotic Cell Components (Plant)					4
2.	Introduction to Biomolecules					5
2.1.	Amino Acids					5
2.1.1.	Essential Amino Acids					9
2.1.2.	Optical Properties					10
2.2.	Carbohydrates					13
2.2.1.	Monosaccharides					13
2.2.2.	Disaccharides					18
2.2.3.	Polysaccharides					19
2.3.	Lipids					22
2.3.1.	Fatty Acids					23
2.3.2.	Triacylglycerols					24
2.3.3.	Phosphoacylglycerols					24
2.3.4.	Sphingolipids					25
2.3.5.	Waxes					26
2.3.6.	Terpenes					26
2.3.7.	Sterols					27
2.3.8.	Prostaglandins					27
2.3.9.	Membranes					27
2.4.	Nucleotides					29
2.4.1.	The Bases					30
2.4.2.	The Sugars					30
2.4.3.	The Nucleosides					31
2.4.4.	The Nucleotides					32
	Reference					34
3.	Protein Structure and Function					35
3.1.	Proteins Are Polymers of Amino Acids, Characterized by Four "Levels" of Structure					36
3.2.	The Protein "Main Chain" Controls Conformational Flexibility					37
3.3.	Common Secondary Structural Elements the Alpha Helix and the Beta Sheet					40
3.4.	Tertiary Structure: Proteins Exhibit Common Folds					42
3.5.	Quaternary Structure					44
3.6.	What Are Protein Structures and How Are Protein Structures Measured?					44
3.7.	Hemoglobin: An Example of Protein Structure and Function					46
3.8.	Protein Folding and Stability					51
	Further Reading					52
4.	Enzymes					53
4.1.	Characteristics of Enzymes					53
4.2.	Enzyme Classification					55
4.3.	Mechanisms of Enzyme Action					56
4.4.	Nucleophilic Substitution Reactions					64
4.4.1.	SN1 (Substitution, Nucleophilic, First Order Reaction)					64
4.4.2.	SN2 (Substitution, Nucleophilic, Second Order)					65
4.4.3.	Stereochemistry of Nucleophilic Substitution Reactions					65
4.5.	Phosphorous Compounds and Their Chemistry					65
4.5.1.	Oxidation States of Phosphorous					66
4.5.2.	Types of Reaction Involving Phosphorous					66
4.6.	Studying the Stereochemistry of Enzyme-Catalyzed Reactions					67
4.6.1.	The Use of Chiral Phosphorous Compounds					67
4.6.2.	Isotope Scrambling (Positional Isotope Exchange)					68
4.7.	Studies on the Mechanism of Enzyme Action Using Transition State Analogs					69
4.7.1.	Proline Racemase					69
4.7.2.	Adenylate Kinase					70
4.7.3.	Lysozyme					71
4.8.	Mechanism of Chymotrypsin					73
4.9.	Specificity of the Serine Proteases					75
4.10.	Low-Barrier Hydrogen Bonds					76
4.11.	Mechanism of Glucoamylase					76
4.12.	Substrate Channeling					77
	References					79
5.	Enzyme Kinetics					81
5.1.	Nomenclature					81
5.2.	Brief Review of Chemical Kinetics					82
5.3.	The Evolution of Enzyme Kinetics					83
5.3.1.	Historical					83
5.3.2.	Time Course of Enzyme-Catalyzed Reactions					84
5.3.3.	Derivation of the Henri--Michaelis--Menten Equation					85
5.3.4.	The Haldane Equation					91
5.3.5.	Shorthand Method for Deriving Rate Equations for the Reverse Reaction					92
5.3.6.	Enzyme Inhibition					92
5.3.7.	Reversible Enzyme Inhibition					93
5.3.8.	The Effect of pH on Enzyme Kinetics					99
5.3.9.	The Effect of Temperature on Enzyme Kinetics					101
5.3.10.	The Integrated Henri--Michaelis--Menten Equation					101
5.3.11.	Kinetic Isotope Effects					103
5.3.12.	Miscellaneous Methods for Studying Enzyme Kinetics					105
5.3.13.	Cooperativity and Sigmoidal Kinetics					106
	References					122
6.	Coenzymes and Vitamins					123
6.1.	Coenzymes					123
6.1.1.	NAD+ and NADP+					123
6.1.2.	Biotin					126
6.1.3.	Thiamine Pyrophosphate					127
6.1.4.	Coenzyme A					129
6.1.5.	Pyridoxal Phosphate					130
6.1.6.	Flavin Coenzymes					133
6.1.7.	Lipoic Acid					135
6.1.8.	Folic Acid Coenzymes					136
6.1.9.	Vitamin B12 Coenzymes					139
6.2.	Vitamins					143
6.2.1.	Vitamin A					143
6.2.2.	Vitamin C					144
6.2.3.	Vitamin D					144
6.2.4.	Vitamin E					145
6.2.5.	Vitamin K					146
	References					148
7.	Introduction to Metabolism					149
7.1.	High Energy Compounds					151
7.1.1.	ATP (as Well as Other Nucleoside Di-and Triphosphates)					152
7.1.2.	Acetyl Phosphate					152
7.1.3.	Creatine Phosphate					153
7.1.4.	Phosphoenolpyruvate					153
7.1.5.	Pyrophosphate					153
7.1.6.	Acetyl-Coenzyme A (Acetyl-CoA)					154
7.2.	Intermediate Energy Compounds					154
7.3.	Low Energy Compounds					155
7.4.	Regeneration of Nucleoside Di- and Tri-Phosphates					155
7.5.	Metabolic Pathways and Their Regulation					156
7.5.1.	The Concept of the "Committed Step" in a Metabolic Pathway					156
7.5.2.	Metabolic Pathways Are Highly Exergonic					157
7.5.3.	Pathways Are Not Thermodynamically Reversible, But They Are Physiologically Reversible					158
7.5.4.	Feed Forward Activation and Feed-Back Inhibition					158
7.5.5.	Equilibrium Versus Nonequilibrium Enzymes as Sites of Regulation					158
7.5.6.	Modulation of Enzyme Activity					159
	References					161
8.	Carbohydrate Metabolism A: Glycolysis and Gluconeogenesis					163
8.1.	Glycolysis					163
8.1.1.	Glycolytic Enzymes and Their Mechanisms of Action					165
8.1.2.	Metabolism of D-Mannose and D-Galactose					176
8.1.3.	Regulation of Glycolysis					180
8.2.	Gluconeogenesis					183
8.2.1.	Pyruvate Carboxylase					184
8.2.2.	Phosphoenolpyruvate Carboxykinase					186
8.2.3.	Fructose-1,6-Bisphosphatase1					187
8.2.4.	Glucose-6-Phosphatase					188
8.3.	Coordinated Regulation Between Glycolysis and Gluconeogenesis					189
8.4.	The Cori Cycle					193
8.5.	The Glucose--Alanine Cycle					194
8.6.	Shuttle Mechanisms Allow Oxaloacetate Transport from Mitochondria to the Cytosol					195
8.7.	The Pentose Phosphate Shunt					196
8.7.1.	The Enzymes of the Pentose Phosphate Shunt					197
8.7.2.	Regulation of the Pentose Phosphate Pathway					202
	References					203
9.	The Tricarboxylic Acid Cycle					205
9.1.	The Conversion of Pyruvate to Acetyl-CoA					206
9.2.	The TCA Cycle: The Fate of Acetyl-CoA					210
9.3.	Energetics of Pyruvate Oxidation					212
9.4.	Stereochemistry of the TCA Cycle					213
9.5.	TCA Cycle Enzymes and Their Mechanisms					214
9.5.1.	Citrate Synthase					214
9.5.2.	Aconitase					215
9.5.3.	Isocitrate Dehydrogenase					216
9.5.4.	α-Ketoglutarate Dehydrogenase					217
9.5.5.	Succinyl-CoA Synthetase					217
9.5.6.	Succinate Dehydrogenase					218
9.5.7.	Fumarase					219
9.5.8.	Malate Dehydrogenase					220
9.6.	Regulation of Acetyl-CoA Oxidation					220
9.6.1.	Pyruvate Dehydrogenase Regulation					220
9.6.2.	TCA Cycle Regulation					221
	References					222
10.	Electron Transport and Oxidative Phosphorylation					223
10.1.	Electron Transport					224
10.2.	Components of the Electron Transport Chain					226
10.2.1.	Coenzyme Q					226
10.2.2.	Iron Sulfur Proteins					228
10.2.3.	The Cytochromes					229
10.3.	Electron and Proton Transport					230
10.4.	The Chemiosmotic Hypothesis					230
10.5.	ATP Synthase					233
10.5.1.	The Binding Change Mechanism					233
10.5.2.	Chemical Mechanism of the ATP Synthase Reaction					235
10.6.	Transport of Nucleotides and Pi Through Mitochondrial Membranes					235
10.7.	The Fate of NADH in Aerobic Tissue					236
10.8.	The Regulation of Oxidative Phosphorylation					237
10.9.	Inhibitors of Oxidative Phosphorylation					237
	References					238
11.	Carbohydrate Metabolism B: Di-, Oligo-, and Polysaccharide Synthesis and Degradation					239
11.1.	Disaccharide Synthesis and Degradation					239
11.1.1.	Sucrose (Table Sugar)					239
11.1.2.	Lactose					241
11.1.3.	Maltose					244
11.2.	Glycogenolysis					245
11.2.1.	Glycogen Phosphorylase					245
11.2.2.	Glucan Transferase					247
11.2.3.	α(1[→]6) Glucosidase (Debranching Enzyme)					248
11.3.	Glycogenesis					249
11.3.1.	Glycogen Synthase					249
11.3.2.	The Branching Enzyme (Amylo-(1,4[→]1,6)-Transglucosylase)					250
11.3.3.	Glycogenin					252
11.4.	Regulation of Glycogen Metabolism					253
11.5.	Regulation of Phosphorylase					253
11.6.	Regulation of Glycogen Synthase					254
11.7.	Synthesis and Degradation of Starch					255
11.8.	Synthesis and Degradation of Cellulose					255
	References					256
12.	Lipid Metabolism					257
12.1.	Lipid Digestion					257
12.2.	Degradation of Fatty Acids					258
12.3.	Transport of Fatty Acids into Mitochondria					260
12.4.	β-Oxidation of Fatty Acids					261
12.5.	Energetics of the β-Oxidation Pathway					262
12.6.	β-Oxidation of Unsaturated Fatty Acids					263
12.7.	Oxidation of Odd Numbered Fatty Acids					263
12.8.	Fatty Acid Biosynthesis					264
12.9.	Comments on the FAS system					266
12.10.	Regulation of Fatty Acid Metabolism					267
12.11.	Triacylglycerol Biosynthesis					268
12.12.	Ketone Body Formation					269
12.13.	Fatty Acid Elongation					271
12.14.	Fatty Acid Desaturation					271
12.15.	Lipoproteins and Lipid Transport					273
12.16.	Cholesterol Biosynthesis					275
12.17.	The Glyoxylate Cycle					276
	References					277
13.	Amino Acid Metabolism					279
13.1.	The Nitrogen Cycle					279
13.2.	Amino Acid Metabolism					280
13.3.	Biosynthesis of the Nonessential Amino Acids					280
13.4.	Amino Acid Degradation					284
13.5.	Essential Amino Acids					285
13.6.	Amino Acids Are Precursors of Metabolic Regulators					286
13.6.1.	Glutathione					286
13.6.2.	Epinephrine					287
13.6.3.	Histamine					287
13.6.4.	Serotonin					287
13.6.5.	Thyroxine					288
13.6.6.	Nitric Oxide					288
13.6.7.	S-adenosylmethionine					288
13.7.	The Krebs Urea Cycle					290
	References					292
14.	Nucleotide Metabolism					293
14.1.	De Novo Pyrimidine Nucleotide Biosynthesis					293
14.1.1.	The Synthesis of Uridine-5'-Monophosphate					293
14.1.2.	Enzymes of Pyridine Nucleotide Biosynthesis					295
14.1.3.	Synthesis of Cytidine Nucleotides					299
14.1.4.	Control of Pyrimidine Nucleotide Biosynthesis					300
14.2.	Pyrimidine Catabolism					302
14.3.	De Novo Purine Nucleotide Biosynthesis					302
14.3.1.	The Biosynthesis of Inosine-5'-Monophosphate					303
14.3.2.	AMP and GMP Biosynthesis					304
14.3.3.	Purine Nucleotide Biosynthesis: Enzyme Mechanisms					305
14.3.4.	Regulation of Purine Nucleotide Biosynthesis					309
14.4.	Deoxyribonucleotide Synthesis and Regulation					310
14.5.	Thymidylate Synthase					312
14.6.	Degradation of Purines					313
14.7.	Purine and Pyrimidine Nucleotide Salvage Pathways					314
	References					314
15.	Photosynthesis					317
15.1.	The Chloroplast					317
15.2.	Light and Its Properties					318
15.3.	Photosynthesis Pigments					319
15.4.	The Photosystems					320
15.4.1.	PSII					321
15.4.2.	PSI					323
15.5.	ATP Synthesis					324
15.6.	The Light Independent Reactions					324
15.7.	The Calvin Cycle					325
15.7.1.	The Mechanism of the Rubisco Reaction					327
15.7.2.	Starch and Sucrose Can Be Used to Synthesize D-Glucose					327
15.7.3.	Regulation of the Calvin Cycle					328
15.7.4.	Comments on the Calvin Cycle					328
	References					329
16.	DNA, RNA, and Protein Metabolism					331
16.1.	DNA					331
16.1.1.	Structure					331
16.1.2.	DNA Replication					334
16.1.3.	Repair of DNA					337
16.1.4.	Degradation of Cellular DNA					338
16.2.	RNA					338
16.2.1.	The Central Dogma Hypothesis					339
16.2.2.	Posttranslational Modification of tRNA, rRNA, and mRNA					341
16.2.3.	Ribozymes					343
16.2.4.	Degradation of RNA					344
16.3.	Protein Metabolism					344
16.3.1.	Protein Synthesis					344
16.3.2.	Intracellular Protein Catabolism					351
	References					351
	Index					353