Metabolism of Drugs and Other Xenobiotics

Preface
 
PART ONE: Biochemistry and Molecular Genetics of Drug Metabolism
 
DRUG-METABOLIZING ENZYMES - AN OVERVIEW
Introduction: Fate of a Drug in the Human Body
Classification Systems of Drug-Metabolizing Enzymes According to Different Criteria
Overview of the Most Important Drug-Metabolizing Enzyme
 
CYTOCHROMES P450
Introduction and Historical Perspective
Nomenclature and Gene Organization
Regulation
Polymorphisms
Protein Structure
Catalytic Mechanisms
What Determines P450 Catalytic Selectivity?
Oxidative Stress and P450s
Relevance in Drug Metabolism and Clinical Medicine
 
UDP-GLUCURONOSYLTRANSFERASES
Introduction
A Simple Phenotype: Unconjugated Nonhemolytic
Hyperbilirubinemia and Glucuronidation
Organization of UGTs and the UGT1A Gene Locus
UGT1A Gene Nomenclature
Human UGT1A Gene Locus and Sequence Variability
Glucuronidation of Bilirubin
UGT1A1 Gene
Is There an Advantage or Risk Associated with UGT1A1 Variability?
UGT1A1 Gene and Pharmacogenetic Protection
UGT1A1 Gene and Pharmacogenetic Risks
UGT1A1 Variability and Cancer Risk
UGT1A3 Gene
UGT1A7 Gene
Transcriptional Regulation of UGT1A Genes
Aryl Hydrocarbon Receptor/Aryl Hydrocarbon Receptor Nuclear Translocator Regulation of UGT1A Genes
Regulation by Hepatic Nuclear Factors
Regulation by the Farnesoid X Receptor
Regulation by Nuclear Factor Erythroid 2-Related Factor 2
Regulation by Splice Variants
Animal Models to Study UGT1A Genes
Outlook
 
SULFOTRANSFERASES
Introduction
Background
PAPS Synthesis
SULT Enzyme Family
Assays for SULT Activity
Structure and Function of SULT
SULT Pharmacogenetics
Bioactivation and the Role of SULTs in Toxicology
Conclusions and Future Perspectives
 
GLUTATHIONE S-TRANSFERASES
Introduction and History
Nomenclature, Structure, and Function
Substrates
Regulation, Induction, and Inhibition
Gene Polymorphism of GSTs
 
HYDROLYTIC ENZYMES
Carboxylesterases
Epoxide

Pavel Anzenbacher heads the Department of Pharmacology at Palacky University, Olomouc (Czech Republic). Having obtained his academic degrees from Charles University, Prague and from the Academy of Sciences of the Czech Republic he joined the Faculty of Medicine at Palacky University. His scientific contacts and stays have included e.g. the Princeton University, University of Connecticut, INSERM Montpellier, University of Lubeck, Technical University Berlin and Cracow University. Professor Anzenbacher has authored over 150 original scientific publications has, among other honours, received the Fogarty Award of the USPHS.

Ulrich M. Zanger is the Deputy Head of the Margarete Fischer Bosch Institute for Clinical Pharmacology, Stuttgart (Germany). A chemist by training, Dr. Zanger began to work on drug metabolism at the Biocenter of the University of Basel, Switzerland, where he obtained a PhD degree in biochemistry in 1988. He undertook postdoctoral studies at the Southwestern Medical Center at Dallas, Texas before returning to Basel and later moving to Stuttgart. His major research interests are in drug metabolism, basic and clinical aspects of pharmacogenetics / genomics, and molecular genetics of human drug metabolizing cytochromes P450. Dr. Zanger has authored more than 130 scientific articles and is lecturing in Pharmacology and Toxicology at the University of Tübingen.cut, INSERM Montpellier, University of Lubeck, Technical University Berlin and Cracow University. Professor Anzenbacher has authored over 150 original scientific publications has, among other honours, received the Fogarty Award of the USPHS.

Ulrich M. Zanger is the Deputy Head of the Margarete Fischer Bosch Institute for Clinical Pharmacology, Stuttgart (Germany). A chemist by training, Dr. Zanger began to work on drug metabolism at the Biocenter of the University of Basel, Switzerland, where he obtained a PhD degree in biochemistry in 1988. He undertook postdoctoral studies at the Southwestern

"Overall therefore, a book which can be read in its own right for the first half and then a valuable source of reference for the second half. A useful tome to have on the bookshelf for anyone in the field." ( British Toxicology Society , 1 July 2013)