Vitamin K (eBook)

Cover 1
Contents 8
Contributors 14
Preface 20
Chapter 1: Determinants of Vitamin K Status in Humans 22
I. Introduction 23
II. Assessment of Vitamin K Status 23
III. Nongenetic Determinants 26
IV. Genetic Determinants 35
V. Conclusions and Future Directions 37
Acknowledgments 38
References 38
Chapter 2: VKORC1 and the Vitamin K Cycle 44
I. Vitamin K Cycle: Limiting Step of Carboxylation 45
II. VKOR: Is It a Complex? 48
III. VKORC1 in Clinical Practice 50
IV. Conclusion 52
Acknowledgment 221
References 221
Chapter 3: The Vitamin K Cycle 56
I. Introduction 57
II. Vitamin K Biosynthesis 58
III. Vitamin K Cycle 60
IV. Physiological Role of Vitamin K Dependent Proteins 65
V. Clinical Phenotypes Related to the Vitamin K Pathway in Man 68
VI. Conclusions and Perspectives 74
Acknowledgments 75
References 75
Chapter 4: Structure, Function, and Mechanism of Cytosolic Quinone Reductases 84
I. Introduction 85
II. Quinone Reductase Type 1 86
III. Quinone Reductase Type 2 98
IV. Disclaimer 100
References 221
Chapter 5: Quinone Oxidoreductases and Vitamin K Metabolism 106
I. Vitamin K and Vitamin K Cycle 107
II. Quinone Oxidoreductases 108
III. Quinone Oxidoreductases and Reduction of Vitamin K to Hydroquinone 112
IV. Quinone Oxidoreductases and Metabolic Detoxification or Activation of Vitamin K 114
V. Quinone Oxidoreductases and Anticancer Effects of Vitamin K 116
VI. Future Perspectives 117
Acknowledgments 221
References 221
Chapter 6: Structure and Function of Vitamin K Epoxide Reductase 124
I. Introduction 125
II. Purification of VKOR 127
III. Mechanism of Vitamin K Epoxide Reduction Catalyzed by VKOR 131
IV. Identification of the Active Site of VKOR 136
V. Warfarin Inhibition of VKOR 138
VI. Membrane Topology of VKOR 143
VII. Conclusion 145
References 146
Chapter 7: Vitamin K Dependent Carboxylation 152
I. Vitamin K-Dependent Protein Function 153
II. Vitamin K Forms 155
III. Mechanism of Carboxylation 156
IV. Functional Regions of the Carboxylase 159
V. Vitamin K Reduction Is Required for Carboxylation in Tissue 163
VI. Carboxylation Interfaces with Secretion 165
VII. The Capacity of Vitamin K-Dependent Protein Carboxylation Is Limited in Cultured Cells 167
VIII. Summary 169
References 221
Chapter 8: Vitamin K-Dependent gamma-Glutamylcarboxylation: An Ancient Posttranslational Modification 178
I. Introduction 179
II. Reviews 180
III. gamma-Carboxylation Reaction 180
IV. Vitamin K Cycle 182
V. Mechanism of gamma-Carboxylation 183
VI. Proposed Topology of gamma-Glutamyl Carboxylase 183
VII. Substrate Recognition (Propeptide) 184
VIII. Structure-Function Relationship 185
IX. Expression of GGCX During Development 187
X. Gla-Containing Proteins and gamma-Carboxylase in Urochordate 187
XI. Drosophila gamma-Glutamyl Carboxylase 188
XII. gamma-Carboxylated Peptides in Conus 188
XIII. Conus gamma-Glutamyl Carboxylase 195
XIV. Future Prospects 196
Acknowledgments 198
References 198
Chapter 9: Vitamin K-De pendent Actions of Gas6 206
I. Introduction 207
II. Gas6 Structure 207
III. Cellular Effects of Gas6 208
IV. Interaction with TAM Receptor Molecules and Signal Transduction in the Gas6/TAM Ligand/Receptor System 212
V. Role of the Gas6/TAM System in Vascular Biology 215
VI. Gas6 in Innate Immunity: A Modulator of the Inflammatory Response 216
VII. Further Functions of Gas6/TAM Receptors in Cellular Homeostasis 218
VIII. Overlapping Functions of Gas6 and Protein S 218
IX. The Implications of Vitamin K in Gas6 Function 220
Acknowledgment 221
References 221
Chapter 10: Vitamin K2-Mediated Apoptosis in Cancer Cells: Role of Mitochondrial Transmembrane Potential 232
I. Introduction 233
II. Growth-Inhibitory Effect of Vitamin K2 234
III. Induction of Differentiation of Leukemia Cells by Vitamin K2 234
IV. Induction of Apoptosis by Vitamin K2 in Human Cancer Cells 235
V. Association with Reduced Mitochondrial Membrane Potential (DeltaPsim) 238
VI. Conclusion 242
References 243
Chapter 11: VKORC1: A Warfarin-Sensitive Enzyme in Vitamin K Metabolism and Biosynthesis of Vitamin K-Dependent Blood Coagulation Factors 248
I. Introduction 249
II. The Vitamin K-Dependent gamma-Carboxylation System 252
III. Genetics of Warfarin Resistance 262
IV. Future Perspectives 263
References 221
Chapter 12: Warfarin Therapy: Influence of Pharmacogenetic and Environmental Factors on the Anticoagulant Response to Warfarin 268
I. Introduction 269
II. Vitamin K and Vitamin K Antagonists and Blood Coagulation 270
III. Pharmacology of Warfarin 272
IV. Influence of Environmental Factors on the Anticoagulant Response to Warfarin 274
V. Influence of Pharmacogenetics on the Anticoagulant Response to Warfarin 278
VI. Conclusion 282
References 221
Chapter 13: Vitamin K and Thrombosis 286
I. Introduction 287
II. Pharmacology of Vitamin K 287
III. Therapeutic Uses of Vitamin K 290
IV. Patients with Major Hemorrhage 292
V. Patients Without Bleeding but Prolonged INR 292
VI. New Physiologic Functions of Vitamin K 295
VII. Warfarin Effects on Vitamin K 296
VIII. Summary 297
References 221
Chapter 14: Congenital Bleeding Disorders of the Vitamin K-Dependent Clotting Factors 302
I. Introduction 304
II. Congenital Prothrombin (Factor II) Deficiency 306
III. Congenital Factor VII Deficiency 324
IV. Congenital Factor IX Deficiency (Hemophilia B) 339
V. Congenital Factor X Deficiency 350
VI. Combined Congenital Deficiency of FII, FVII, FIX, FX 368
VII. Deficiency of Protein Z 375
VIII. Conclusions 376
References 221
Chapter 15: Role of Growth Arrest-Specific Gene 6 in Diabetic Nephropathy 396
I. Introduction 397
II. Role of Gas6 in STZ-I nduced Diabetic Rats 398
III. In Vitro Effect of Gas6 in Mesangial Cells 402
IV. Role of the Akt Pathway in Diabetic Nephropathy 403
V. High Glucose Induces Mesangial Hypertrophy Via Gas6/Axl In Vitro 407
VI. Study Using Gas6-Knockout Mice 409
VII. Conclusions 410
Acknowledgments 412
References 412
Chapter 16: Vitamin K and Bone Health in Adult Humans 414
I. Introduction 415
II. Vitamin K Intake and Bone Health 418
III. Reasons for the Inconsistent Results 426
IV. Vitamin K Recommendations 429
V. Anticoagulation Treatment and Risk of Osteoporosis 430
VI. Interactions Between Vitamin K and Vitamin D 431
VII. Discussion and Conclusion 432
References 432
Chapter 17: Diagnosis of Osteoporosis with Vitamin K as a New Biochemical Marker 438
I. Introduction 439
II. The Important Role of Vitamin K in Bone Metabolism 442
III. Biochemical Markers as Indices of Bone Turnover 449
Acknowledgments 450
References 221
Chapter 18: Hepatocellular Carcinoma and Vitamin K 456
I. Introduction 456
II. Antitumor Effects of VK 457
III. Mechanism of Growth Inhibition of HCC Cells by VK2 458
IV. Analysis of Tumor Recurrence Suppression Following Liver Cancer Treatment 460
V. Future Tasks 461
References 221
Index 464