ABSTRACT

Compiling landmark research from those laying the foundation for medical science's next leap forward, Thiamine: Catalytic Mechanisms in Normal and Disease States fully explores the pathophysiological aspects of a spectrum of diseases associated with TDP-requiring enzymes. Providing brilliant new insights into neurogenerative diseases, this comprehensive volume associates defects in the function of TDP-dependent enzymes with numerous metabolic disorders and disease states, and offers novel aspects of thiamine enzymes in chiral synthesis, as well as new perspectives on the cellular role of thiamine triphosphate and thiamine triphosphates.

Series Introduction, Preface, Contributors, Part I: Introduction, 1. Chemical Intermediates in Catalysis by Thiamine Diphosphate, Part II: Biosynthesis of Thiamine and Its Phosphorylated Terms 2. Mechanistic and Structural Studies on Thiamine Biosynthetic Enzymes, 3. Studies on the Structure and Function of Thiamine Pyrophosphokinase, 4. New Perspectives on the Cellular Role of Thiamine Triphosphate and Thiamine Triphosphatase, Part III: Enzymology of Thiamine Diphosphate Enzymes, 5. How Thiamine Works in Enzymes: Time-Resolved NMR Snapshots of TDP-Dependent Enzymes in Action, 6. Thiamine-Dependent Enzymes as Catalysts of C C Bond-Forming Reactions: The Role of “Orphan” Enzymes, 7. Ligand-Induced Conformational Changes in Thiamine Diphosphate-Dependent Enzymes: Comparison Between Crystal and Solution Structures, 8. Enantioselective Synthesis of Hydroxy Ketones via Benzoylformate Decarboxylase and Benzaldehyde Lyase-Catalyzed C-C Bond Formation, 9. Benzoylformate Decarboxylase: Lessons in Enzymology, 10. New Concept on the Nature of the Induced Absorption Band of Holotransketolase, 11. Structure of the a-Carbanion/Enamine Reaction Intermediate in the Active Site of Transketolase, Determined by Kinetic Crystallography, 12. Yeast Pyruvate Decarboxylase: New Features of the Structure and Mechanism, 13. Solvent and Carbon Kinetic Isotope Effects on Active-Site and Regulatory Site Variants of Yeast Pyruvate Decarboxylase, 14. Insights into the Mechanism and Regulation of Bacterial Acetohydroxyacid Synthases, 15. Structure and Properties of Acetohydroxyacid Synthase, 16. Exploring the Substrate Specificity of Benzoylformate Decarboxylase, Pyruvate Decarboxylase, and Benzaldehyde Lyase, 17. Benzoylformate Decarboxylase: Intermediates, Transition States, and Diversions, Part IV: Structure and Function of Thiamine Diphosphate Multienzyme Complexes, 18. Structural and Functional Organization of PyruvateDehydrogenase Complexes, 19. The Pyruvate Dehydrogenase Multienzyme Complex, 20. Activation and Transfer of Lipoic Acid in Protein Lipoylation in Mammals, 21. Central Organization of Mammalian Pyruvate Dehydrogenase (PD) Complex and Lipoyl Domain-Mediated Activated Function and Control of PD Kinases and Phosphatase, 22. Physiological Effects of Replacing the PDH Complex of E. coli by Genetically Engineered Variants or by Pyruvate Oxidase, 23. Structure and Intersubunit Information Transfer in the E. coli Pyruvate Dehydrogenase Multienzyme Complex, 24. Structure, Function, and Regulation of Pyruvate Dehydrogenase Kinase, 25. Three-Dimensional Structures for Components and Domain of the Mammalian Branched-Chain a-Ketoacid Dehydrogenase Complex, Part V: Biomedical Aspects of Thiamine Diphosphate Dependent Enzymes, 26. Variability of Human Pyruvate Dehydrogenase Complex Deficiency, 27. Kinetic Studies of Human Pyruvate Dehydrogenase and Its Mutants: Interactions with Thiamine Pyrophosphate, 28. The Complexity of Single-Gene Disorders: Lessons from Maple Syrup Urine Disease and Thiamine Responsiveness, 29. Thiamine Pyrophosphate: An Essential Cofactor in the Mammalian Metabolism of 3-Methyl-Branched Fatty Acids, 30. Pathogenesis of Selective Neuronal Loss in Wemicke Korsakoff Syndrome: Role of Oxidative Stress, 31. Thiamine-Responsive Megaloblastic Anemia Syndrome: Clinical Aspects and Molecular Genetics, Part VI: Concluding Remarks, 32. Accomplishments and Future Directions, Index