Topics in Dental Biochemistry (eBook)

Topics in DentalBiochemistry 2
Copyrightpage 3
Dedication 4
Preface 5
Contents 7
1: Necessary Basics: Elements, Isotopes, Ions, Chemical Reactions, Energy Metabolism, and Bacterial Structures 12
1.1.1. Atomic Structure: Elements and Isotopes 12
1.1.2. Isotopes Date Paleontology Samples Such as Teeth 15
1.1.3. Isotopes Indicate Ancient Life Forms and Climate Changes 16
1.1.4. The Elements in Biology 16
1.1.5. Fluorides 17
1.2.1. Chemical Bonds 17
1.2.2. Electrostatic Bonds 17
1.2.3. Covalent Bonds 18
1.2.4. Polarized Covalent Bonds 18
1.2.5. Hydrophobic Bonds 19
1.3.1. Mechanisms of Energy Production: Respiration and Fermentation 20
1.3.2. The Oral Microbiota, Dental Caries, and Periodontal Disease 21
1.4.1. Bacterial Cell Structures 25
1.4.2. The Bacterial Outer Surface 25
2: Photosynthesis and Sucrose Production 28
2.1.1. Role of Photosynthesis in Living Organisms 28
2.1.2. The Light Reaction 29
2.2.1. The Dark Reaction 32
2.2.2. Starch and Sucrose Provide the Carbon Skeletons of All Plant Compounds 35
2.2.3. Plants Are Autotrophs 35
2.3.1. Sucrose Is the Primary Transport Sugar and Plays a Central Role in Plant Growth and Development 37
3: The Connective Tissue Extracellular Matrix and Its Major Components 39
3.1.1. Major Components of the Connective Tissue (Stromal) Matrix 39
3.1.2. Collagen 40
3.1.3. Elastic Fiber System 44
3.1.4. Glycosaminoglycans 46
3.1.5. Alveolar Bone, Teeth, and Periodontium 46
3.2.1. Cell Surface Binding: Integrins, Fibronectin, and Collagen 50
3.2.2. Thrombospondins and Transforming Growth Factor-ß 51
3.3.1. Stromal Nutrition 53
3.3.2. Stromal Turnover, Inflammation, and Bone Loss 54
4: Fibrillar and Non-fibrillar Collagens and Integrins 55
4.1.1. Fibrillar Collagens 55
4.2.1. Collagen Fiber Formation 60
4.2.2. Fiber Cross-Linking: Formation of b- and g-Tropocollagen 62
4.3.1. The Collagen Superfamily 65
4.3.2. Fiber-Modifying Non-fibrillar Collagens 65
4.3.3. General Structure of Non-fibrous Collagens 66
4.3.4. Beaded Collagen Filaments 66
4.4.1. Integrins and Regulation of Stromal Composition 68
5: Basal Laminas and Epithelia 74
5.1.1. Basal Lamina and its Stromal Attachment 74
5.1.2. Hemidesmosomal Proteins 76
5.1.3. Basal Lamina of the Dental Epithelial Attachment 80
5.2.1. General Structure of Skin, Oral and Junctional Epithelia 82
6: Elastic Fibers and Proteoglycans 90
6.1.1. Fibrillin 90
6.2.1. Elastin 94
6.3.1. Glycosaminoglycans 98
6.4.1. Proteo-Glycosaminoglycan Core Proteins and Cartilage Collagens 104
6.5.1. Major Collagen–Glycosaminoglycan Interactions 107
7: Collagen Synthesis, Genetic Diseases, and Scurvy 109
7.1.1. Intracellular Collagen Synthesis 109
7.2.1. Effects of Collagen Polypeptide Mutations 112
7.2.2. Ehlers-Danlos syndrome (EDS) 113
7.3.1. Ascorbate and Antioxidants 117
8: The Zincins: Collagen Fiber Processing and Degradation 121
8.1.1. The Zincin Enzyme Family 121
8.1.2. Catalytic Action of the Metzincin Family 123
8.1.3. Metzincin Activation 125
8.2.1. Fibrillar Procollagen Processing 128
8.3.1. Matrilysins (MMPs) Hydrolyze Collagen and Stromal Proteins 132
8.3.2. Stromelysins 134
8.3.3. Enamelysin 134
8.3.4. Collagenases and Gelatinases 135
9: Biological Mineralization 137
9.1.1. Fundamental Properties of Calcium Phosphate Precipitation 137
9.1.2. Nature of the Apatite Precipitate 138
9.1.3. Apatite Crystal Substitutions Influence Bone Strength and Solubility 139
9.1.4. Nucleation 139
9.2.1. The Structures of Bone, Dentin, and Cementum 140
9.2.2. Two Mechanisms of Mineralization 142
9.3.1. Secretion of Osteoid Matrix 142
9.3.2. Osteoblast Transport of Calcium and Phosphate Ions to Matrix Vesicles 144
9.3.3. Calcium and Phosphate Ions Precipitate and Rupture Secreted Matrix Vesicles 146
9.3.4. Structure of the Calcium Transporter Proteins in Matrix Vesicles 146
9.3.5. The Phosphate Transporter Proteins and Pyrophosphate in Matrix Vesicles 148
9.4.1. Non-collagenous Bone Proteins in Bone and Dentin 150
9.4.2. Osteocalcin Is Required for Bone Modeling 151
9.5.1. Enamel Organ and Matrix Development 152
9.5.2. Proteins Involved in Enamel Synthesis 154
9.5.3. Proposed Mechanism of Enamel Synthesis 155
9.6.1. Summary of Ways in Which Enamel and Bone Differ 158
9.6.2. Summary of the Vitamins for Bone and Enamel Formation 159
10: Bone Remodeling and Calcium Metabolism 160
10.1.1. Bone Turnover, Osteoclasts, and Lysosomes 160
10.1.2. Proteolysis in the Bone Resorbing Compartment 164
10.1.3. Demineralization and remineralization 164
10.1.4. Osteoclast Ion and Proton Transport 166
10.2.1. Osteoclast Differentiation 167
10.2.2. Osteoclasts and Inflammation 168
10.2.3. Osteoporosis: Major Causes and Therapies 170
10.3.1. Calcium Metabolism, Parathyroid Hormone, and Calcitriol 172
10.4.1. Vitamin D, Calcitriol, and Calbindins 175
10.4.2. Rickets and Osteomalacia 178
10.5.1. Actions of Calcitonin 179
10.5.2. Calcitonin and PTH Therapy for Osteoporosis 180
11: Blood Coagulation 181
11.1.1 The Vascular System 181
11.1.2 Bleeding and Blood Clotting Problems 182
11.2.1 Blood Vessel Injury, von Willebrand Factor, and Platelets 184
11.2.2 The Gamma-Carboxyglutamate Domain: A Calcium Ion Chelator 186
11.3.1 The Extrinsic, Intrinsic, and Common Coagulation Pathways 189
11.3.2 The Extrinsic Pathway 189
11.3.3 The Intrinsic Pathway 191
11.3.4 The Common Pathway 191
11.3.5 The Hemophiliac (Excessive Bleeding Diseases) 193
11.4.1 The Fibrin Blood Clot: Production and Prevention 194
11.4.2 Removal of a Blood Clot 196
11.5.1 Prevention of Unwanted Blood Clotting 198
11.5.2 Thrombomodulin and Protein C and Protein S 201
11.6.1 Drugs to Remove a Pathogenic Thrombus or Embolus: “Clot Busters” 202
11.6.2 Drugs That Inhibit Excessive Clot Formation 204
11.6.3 Drugs That Retard Clot Formation 204
11.6.4 Drugs That Inhibit Platelet Activation 205
11.6.5 Drugs That Promote Clotting 205
11.6.6 Laboratory Tests to Determine the State of the Blood Clotting System 206
12: Saliva 208
12.1.1. Cell Biology of Salivary Glands 208
12.1.2. Whole Saliva: Collection and Composition 208
12.1.3. Functions of the Salivary Components 210
12.1.4. Innate and Acquired Immune Proteins in Saliva 212
12.1.5. Poor Oral Hygiene Adds Bacteria and host leukocyte Products to Saliva 213
12.2.1. Physiology and Biochemistry of Saliva Secretion 214
12.3.1. Salivary Mucin Composition 216
12.3.2. Glycan Composition of Salivary Mucins 218
12.4.1. Mucin Glycans, ABO Antigens, and Forensic Dentistry 221
12.5.1. Amylase: Substrates, Products, and Mode of Action 224
12.5.2. Mechanism of Action of Salivary Amylase 226
12.5.3. Detection of Salivary and Pancreatic Amylase 230
12.6.1. Proline-Rich Proteins 232
12.6.2. Salivary Agglutinin 233
13: Chronic Periodontitis 236
13.1.1 Detecting Periodontal Disease 236
13.1.2 Gingivitis and Chronic Periodontitis in Humans and Animals 237
13.1.3 Microbiota of Gingivitis and Chronic Periodontitis in Man 238
13.1.4 Drugs to Prevent Gingivitis 241
13.2.1 Mammalian Cells Recognize Prokaryotic Molecules 242
13.2.2 PAMPs Induce PRRs to Release Cytokines That Attract Leukocytes 243
13.2.3 IL-1: A Host Mediator of Gingival Inflammation 246
13.2.4 Neutrophils Function in Tissue Destruction 246
13.2.5 Gingivitis is Reversible Antiinflammatory Cytokines Mediate Repair
13.3.1 Long-term Effects of Persistent PAMP Stimulation 249
13.4.1 Apoptosis in Chronic Periodontitis 251
13.4.2 Intracellular Induction of Apoptosis 252
13.4.3 Mechanisms of Apoptosis 254
13.5.1 Eicosanoids and Periodontal Repair 257
13.5.2 Eicosanoid Structure 257
13.5.3 Functions of the Proinflammatory Eicosanoids 260
13.5.4 Lipoxygenase-Mediated Resolution of Inflammation 260
13.5.5 Antiinflammatory Drugs 262
14: Aggressive Periodontitis 264
14.1.1. Generalized Aggressive Periodontitis 264
14.2.1. Localized Aggressive Periodontitis 265
14.2.2. Aa Leukotoxin Composition and Properties 266
14.2.3. Mutations Enhance Aa Ltx and LAP Severity 268
14.2.4. Cytolethal Distending Toxin (Cdt) 269
15: Dental Caries 272
15.1.1. Dental Caries: Definition and Measurement 272
15.1.2. Sugar, Dental Caries, and the Dental Profession 272
15.1.3. Sucrose and the Appearance of Acid in Dental Biofilms 274
15.1.4. Cavities in Animals and Streptococcus mutans 275
15.2.1. How Sucrose Connects S. mutans to the Oral Microbiota and Dental Caries 277
15.2.2. Sources of Bacterial Lactic Acid in Caries 282
15.2.3. Dentinal (Advanced) Dental Caries 282
15.3.1. Variation in Individual Human Caries Experience 283
15.3.2. Bacterial Causes of the Variation in Caries Susceptibility 284
15.3.3. Saliva Causes of Caries Susceptibility 286
15.3.4. Caries Immunity and Susceptibility 287
16: Fluoride 289
16.1.1.Properties of Fluorine and Fluoride 289
16.1.2. How Mottled Enamel Relates to Fluoride in the Water Supply 290
16.1.3. Mottled Enamel Is Moderate to Severe Enamel Fluorosis 291
16.1.4. Identification of 1 ppm Fluoride in the Water as Optimal for Cavity Protection 293
16.2.1. Mechanisms of Fluoride Protection from Caries 295
16.2.2. How Fluoride Protects from Caries 296
16.3.1. Systemic Effects of Fluoride 298
16.3.2. Fluoride Toxicity 299
Index 302