Vitamin K
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Table of contents
- Contentsvii
- Contributorsxiii
- Prefacexix
- Chapter 1: Determinants of Vitamin K Status in Humans1
- I. Introduction2
- II. Assessment of Vitamin K Status2
- III. Nongenetic Determinants5
- IV. Genetic Determinants14
- V. Conclusions and Future Directions16
- Acknowledgments17
- References17
- Chapter 2: VKORC1 and the Vitamin K Cycle23
- I. Vitamin K Cycle: Limiting Step of Carboxylation24
- II. VKOR: Is It a Complex?27
- III. VKORC1 in Clinical Practice29
- IV. Conclusion31
- Acknowledgment200
- References200
- Chapter 3: The Vitamin K Cycle35
- I. Introduction36
- II. Vitamin K Biosynthesis37
- III. Vitamin K Cycle39
- IV. Physiological Role of Vitamin K Dependent Proteins44
- V. Clinical Phenotypes Related to the Vitamin K Pathway in Man47
- VI. Conclusions and Perspectives53
- Acknowledgments54
- References54
- Chapter 4: Structure, Function, and Mechanism of Cytosolic Quinone Reductases63
- I. Introduction64
- II. Quinone Reductase Type 165
- III. Quinone Reductase Type 277
- IV. Disclaimer79
- References200
- Chapter 5: Quinone Oxidoreductases and Vitamin K Metabolism85
- I. Vitamin K and Vitamin K Cycle86
- II. Quinone Oxidoreductases87
- III. Quinone Oxidoreductases and Reduction of Vitamin K to Hydroquinone91
- IV. Quinone Oxidoreductases and Metabolic Detoxification or Activation of Vitamin K93
- V. Quinone Oxidoreductases and Anticancer Effects of Vitamin K95
- VI. Future Perspectives96
- Acknowledgments200
- References200
- Chapter 6: Structure and Function of Vitamin K Epoxide Reductase103
- I. Introduction104
- II. Purification of VKOR106
- III. Mechanism of Vitamin K Epoxide Reduction Catalyzed by VKOR110
- IV. Identification of the Active Site of VKOR115
- V. Warfarin Inhibition of VKOR117
- VI. Membrane Topology of VKOR122
- VII. Conclusion124
- References125
- Chapter 7: Vitamin K Dependent Carboxylation131
- I. Vitamin K-Dependent Protein Function132
- II. Vitamin K Forms134
- III. Mechanism of Carboxylation135
- IV. Functional Regions of the Carboxylase138
- V. Vitamin K Reduction Is Required for Carboxylation in Tissue142
- VI. Carboxylation Interfaces with Secretion144
- VII. The Capacity of Vitamin K-Dependent Protein Carboxylation Is Limited in Cultured Cells146
- VIII. Summary148
- References200
- Chapter 8: Vitamin K-Dependent gamma-Glutamylcarboxylation: An Ancient Posttranslational Modificatio157
- I. Introduction158
- II. Reviews159
- III. gamma-Carboxylation Reaction159
- IV. Vitamin K Cycle161
- V. Mechanism of gamma-Carboxylation162
- VI. Proposed Topology of gamma-Glutamyl Carboxylase162
- VII. Substrate Recognition (Propeptide)163
- VIII. Structure-Function Relationship164
- IX. Expression of GGCX During Development166
- X. Gla-Containing Proteins and gamma-Carboxylase in Urochordate166
- XI. Drosophila gamma-Glutamyl Carboxylase167
- XII. gamma-Carboxylated Peptides in Conus167
- XIII. Conus gamma-Glutamyl Carboxylase174
- XIV. Future Prospects175
- Acknowledgments177
- References177
- Chapter 9: Vitamin K-De pendent Actions of Gas6185
- I. Introduction186
- II. Gas6 Structure186
- III. Cellular Effects of Gas6187
- IV. Interaction with TAM Receptor Molecules and Signal Transduction in the Gas6/TAM Ligand/Receptor191
- V. Role of the Gas6/TAM System in Vascular Biology194
- VI. Gas6 in Innate Immunity: A Modulator of the Inflammatory Response195
- VII. Further Functions of Gas6/TAM Receptors in Cellular Homeostasis197
- VIII. Overlapping Functions of Gas6 and Protein S197
- IX. The Implications of Vitamin K in Gas6 Function199
- Acknowledgment200
- References200
- Chapter 10: Vitamin K2-Mediated Apoptosis in Cancer Cells: Role of Mitochondrial Transmembrane Poten211
- I. Introduction212
- II. Growth-Inhibitory Effect of Vitamin K2213
- III. Induction of Differentiation of Leukemia Cells by Vitamin K2213
- IV. Induction of Apoptosis by Vitamin K2 in Human Cancer Cells214
- V. Association with Reduced Mitochondrial Membrane Potential (DeltaPsim)217
- VI. Conclusion221
- References222
- Chapter 11: VKORC1: A Warfarin-Sensitive Enzyme in Vitamin K Metabolism and Biosynthesis of Vitamin227
- I. Introduction228
- II. The Vitamin K-Dependent gamma-Carboxylation System231
- III. Genetics of Warfarin Resistance241
- IV. Future Perspectives242
- References
- Chapter 12: Warfarin Therapy: Influence of Pharmacogenetic and Environmental Factors on the Anticoag247
- I. Introduction248
- II. Vitamin K and Vitamin K Antagonists and Blood Coagulation249
- III. Pharmacology of Warfarin251
- IV. Influence of Environmental Factors on the Anticoagulant Response to Warfarin253
- V. Influence of Pharmacogenetics on the Anticoagulant Response to Warfarin257
- VI. Conclusion261
- References
- Chapter 13: Vitamin K and Thrombosis265
- I. Introduction266
- II. Pharmacology of Vitamin K266
- III. Therapeutic Uses of Vitamin K269
- IV. Patients with Major Hemorrhage271
- V. Patients Without Bleeding but Prolonged INR271
- VI. New Physiologic Functions of Vitamin K274
- VII. Warfarin Effects on Vitamin K275
- VIII. Summary276
- References
- Chapter 14: Congenital Bleeding Disorders of the Vitamin K-Dependent Clotting Factors281
- I. Introduction283
- II. Congenital Prothrombin (Factor II) Deficiency285
- III. Congenital Factor VII Deficiency303
- IV. Congenital Factor IX Deficiency (Hemophilia B)318
- V. Congenital Factor X Deficiency329
- VI. Combined Congenital Deficiency of FII, FVII, FIX, FX347
- VII. Deficiency of Protein Z354
- VIII. Conclusions355
- References
- Chapter 15: Role of Growth Arrest-Specific Gene 6 in Diabetic Nephropathy375
- I. Introduction376
- II. Role of Gas6 in STZ-I nduced Diabetic Rats377
- III. In Vitro Effect of Gas6 in Mesangial Cells381
- IV. Role of the Akt Pathway in Diabetic Nephropathy382
- V. High Glucose Induces Mesangial Hypertrophy Via Gas6/Axl In Vitro386
- VI. Study Using Gas6-Knockout Mice388
- VII. Conclusions389
- Acknowledgments391
- References391
- Chapter 16: Vitamin K and Bone Health in Adult Humans393
- I. Introduction394
- II. Vitamin K Intake and Bone Health397
- III. Reasons for the Inconsistent Results405
- IV. Vitamin K Recommendations408
- V. Anticoagulation Treatment and Risk of Osteoporosis409
- VI. Interactions Between Vitamin K and Vitamin D410
- VII. Discussion and Conclusion411
- References411
- Chapter 17: Diagnosis of Osteoporosis with Vitamin K as a New Biochemical Marker417
- I. Introduction418
- II. The Important Role of Vitamin K in Bone Metabolism421
- III. Biochemical Markers as Indices of Bone Turnover428
- Acknowledgments429
- References
- Chapter 18: Hepatocellular Carcinoma and Vitamin K435
- I. Introduction435
- II. Antitumor Effects of VK436
- III. Mechanism of Growth Inhibition of HCC Cells by VK2437
- IV. Analysis of Tumor Recurrence Suppression Following Liver Cancer Treatment439
- V. Future Tasks440
- References
- Index443
Vitamin K, one of the group of fat-soluble vitamins (A, D, E and K), has come into prominence lately because its activity as a blood coagulation factor impinges on the widespread occurrence of deep vein thrombosis in the human population especially in the older age group. This volume focuses, not only on the problem of blood coagulation and hypercoagulability, but upon the individual status of vitamin K in the human.
First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists.
*Focuses on the problem of blood coagulation and hypercoagulability as well as bone metabolism and vascular biology
*In the category of basic science, contributions cover: VKOR1, the quinone reductases including structure, function and mechanism, vitamin K-dependent carboxylation, the actions of Gas6, vitamin K2-mediated apoptosis and other topics
*In the category of disease-related subjects, contributions cover warfarin therapy, diabetic nephropathy, bone health, including osteoporosis and tumor cell suppression, as well as other topics
First published in 1943, Vitamins and Hormones is the longest-running serial published by Academic Press. Under the capable and qualified editorial leadership of Dr. Gerald Litwack, Vitamins and Hormones continues to publish cutting-edge reviews of interest to endocrinologists, biochemists, nutritionists, pharmacologists, cell biologists, and molecular biologists.
*Focuses on the problem of blood coagulation and hypercoagulability as well as bone metabolism and vascular biology
*In the category of basic science, contributions cover: VKOR1, the quinone reductases including structure, function and mechanism, vitamin K-dependent carboxylation, the actions of Gas6, vitamin K2-mediated apoptosis and other topics
*In the category of disease-related subjects, contributions cover warfarin therapy, diabetic nephropathy, bone health, including osteoporosis and tumor cell suppression, as well as other topics