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Cytochrome P450 2D6
Structure, Function, Regulation and Polymorphism
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Main description:

Cytochromes are proteins that catalyze electron transfer reactions of well-known metabolic pathways and are classified in various superfamilies. The CYP, or P450, superfamily accounts for 90% of the oxidative metabolism of clinical drugs. One member of this superfamily, P450 2D6 (or CYP2D6), singlehandedly metabolizes about 25% of all medications in the human liver. Cytochrome P450 2D6: Structure, Function, Regulation, and Polymorphism reviews the current knowledge of CYP2D6 as well as the maturing body of evidence indicating its significance to clinical and pharmacological researchers and practitioners. This book focuses on the critical role CYP2D6 plays in the human liver. It examines the genetic, epigenetic, physiological, pathological, and structural factors of the gene that govern the highly variable metabolism of a number of drugs in clinical use. It highlights the impact of the functional roles of CYP2D6 on clinical practice and drug development and also discusses implications for precise medicine, strategies to avoid adverse drug reactions, and paths for future research. Cytochrome P450 2D6 is a unique, valuable book focusing on a single but immensely powerful human gene.
It provides the first single source of comprehensive information on CYP2D6 that serves as an important reference for medical, biomedical, pharmaceutical, and nursing researchers, practitioners, and students.


Contents:

Introduction to Human Cytochrome P450 Superfamily The Cytochrome P450s in Nature Human CYP Superfamily Human CYP1 Family Human CYP2ABFGST Cluster: CYP2A6, 2A7, 2A13, 2B6, 2F1, and 2S1 Human CYP2C Cluster: CYP2C8, 2C9, 2C18, and 2C19 Other Human CYP2 Family Members Human CYP3A Cluster: CYP3A4, 3A5, 3A7, and 3A43 Human CYP4ABXZ Cluster: CYP4A11, 4A22, 4B1, 4X1, and 4Z1 Human CYP4F Cluster: CYP4F2, 4F3, 4F8, 4F11, 4F12, and 4F22 Other Human CYP4 Family Members Human CYP5 Family Human CYP7 Family Human CYP8 Family Human CYP11 Family Human CYP17 Family Human CYP19 Family Human CYP20 Family Human CYP21 Family Human CYP24 Family Human CYP26 Family Human CYP27 Family Human CYP39A1, 46A1, and 51A1 Human CYP46 Family Human CYP51 Family Highlights of This Book References Mammalian CYP2D Members: A Comparison of Structure, Function, and Regulation Introduction Rat Cyp2d Subfamily: Cyp2d1, 2d2, 2d3, 2d4, and 2d5 Mouse Cyp2d Subfamily: Cyp2d9-2d13, 2d22, 2d26, 2d34, and 2d40 Bovine CYP2D14 Dog CYP2D15 Guinea Pig Cyp2d16 Macaque CYP2D17, 2D29, 2D42, and 2D44 Marmoset CYP2D8, 2D19, and 2D30 Rabbit CYP2D23 and CYP2D24 Pig CYP2D25 Syrian Hamster Cyp2d27 Chicken CYP2D49 Horse CYP2D50 Conclusions and Future Perspectives References Substrates of Human CYP2D6 Introduction Probes of CYP2D6 Therapeutic Drugs as Substrates of CYP2D6 Drugs of Abuse as Substrates of CYP2D6 Fluorescent Probes as Substrates of CYP2D6 Plant Alkaloids, Toxicants, and Environmental Compounds as Substrates of CYP2D6 Endogenous Compounds as Substrates of CYP2D6 Structure-Activity Relationships of CYP2D6 Substrates Conclusions and Future Directions References Inhibitors of Human CYP2D6 Introduction Selective Inhibitors of CYP2D6 Reversible and Mixed-Type Inhibitors of CYP2D6 Structure-Activity Relationships of CYP2D6 Inhibitors Conclusions and Future Directions References Regulation of Human CYP2D6 Introduction Effects of Physiological Factors on CYP2D6 Activity Effects of Environmental Factors on CYP2D6 Activity Human CYP2D6 Is Largely Uninducible by Prototypical Inducers of CYPs Transcriptional and Posttranscriptional Regulation of CYP2D6 by HNF-4alpha and FXR Posttranslational Regulation of CYP2D6 Genome-Wide Association Studies on the Regulation of CYP2D6 Effects of Diseases on CYP2D6 Expression and Activity Conclusions and Future Directions References Structure and Function of Human CYP2D6 Introduction Pharmacophore Models and Structural Requirements of CYP2D6 Ligands Homology Modeling Studies of Human CYP2D6 Site-Directed Mutagenesis Studies of CYP2D6 Studies Using Aryldiazene Probes Antibody Studies of Human CYP2D6 Other Molecular Modeling Studies X-ray Crystallographic Study of Human CYP2D6 and Functional Implications Bindings Modes of the Substrates and Inhibitors with CYP2D6 Conclusions and Future Directions References Clinical Pharmacogenomics of Human CYP2D6 Introduction Interindividual Variability in CYP2D6 Expression and Activity Alleles of the CYP2D6 Gene Ethnic Variation in the Distribution of CYP2D6 Polymorphisms Antianginal Drugs Antiarrhythmic Drugs Antidepressants Antipsychotics Centrally Acting Cholinesterase Inhibitors Drugs for the Treatment of Attention-Deficit/Hyperactivity Disorder Drugs for the Treatment of Senile Dementia Antimuscarinic Drugs Antiemetics Antihistamine ss-Blockers Opioids Oral Hypoglycemic Drugs Selective Estrogen Receptor Modulators Other Drugs Conclusions and Future Perspectives References General Discussion about Human CYP2D6 References


PRODUCT DETAILS

ISBN-13: 9781466597884
Publisher: Taylor & Francis (CRC Press Inc)
Publication date: February, 2016
Pages: 500

Subcategories: Gastroenterology, Pharmacology