Phase II Conjugation Enzymes and Transport Systems

This volume on conjugation enzymes and transporters serves to bring together current methods and concepts in an interesting, important and rapidly developing field of cell and systems biology. Phase II Conjugation Enzymes and Transport Systems focuses on the so-called Phase II enzymes of drug metabolism (xenobiotics), which has important ramifications for endogenous metabolism and nutrition. Also included are aspects on Phase III, transport systems. This volume of Methods in Enzymology presents current knowledge and methodology on glucuronidation, sulfation, acetylation, and transport systems in this field of research. Together with the volumes on Quinones and Quinone Enzymes (volumes 378 and 382), and on Glutathione Transferases and gamma-Glutamyl Transpeptidases (volume 401), the state of knowledge on proteomics and metabolomics of many pathways of (waste) product elimination, enzyme protein induction and gene regulation and feedback control is provided. This volume will help stimulate future investigations and speed the advance of knowledge in systems biology.

Autorentext
Helmut Sies, MD, PhD (hon), studied medicine at the universities of Tübingen, Munich, and Paris. He was the professor and chair of the Institute for Biochemistry and Molecular Biology I at Heinrich-Heine-University Düsseldorf, Germany, where he is now professor emeritus. He is a member of the German National Academy of Sciences Leopoldina and was the president of the North Rhine-Westphalian Academy of Sciences and Arts. He was named 'Redox Pioneer'; was the president of the Society for Free Radical Research International (SFRRI). Helmut Sies introduced the concept of Oxidative Stress” in 1985, and was the first to reveal hydrogen peroxide as a normal constituent of aerobic cell metabolism. His research interests comprise redox biology, oxidants, antioxidants, micronutrients.Lester Packer received a PhD in Microbiology and Biochemistry in 1956 from Yale University. In 1961, he joined the University of California at Berkeley serving as Professor of Cell and Molecular Biology until 2000, and then was appointed Adjunct Professor, Pharmacology and Pharmaceutical Sciences, School of Pharmacy at the University of Southern California. Dr Packer received numerous distinctions including three honorary doctoral degrees, several distinguished Professor appointments. He was awarded Chevalier de l'Ordre National du Merite (Knight of the French National Order of Merit) and later promoted to the rank of Officier. He served as President of the Society for Free Radical Research International (SFRRI), founder and Honorary President of the Oxygen Club of California. He has edited numerous books and published research; some of the most cited articles have become classics in the field of free radical biology: Dr Packer is a member of many professional societies and editorial boards. His research elucidated - the Antioxidant Network concept. Exogenous lipoic acid was discovered to be one of the most potent natural antioxidants and placed as the ultimate reductant or in the pecking order of the Antioxidant Network” regenerating vitamins C and E and stimulating glutathione synthesis, thereby improving the overall cellular antioxidant defense. The Antioxidant Network is a concept addressing the cell's redox status. He established a world-wide network of research programs by supporting and co-organizing conferences on free radical research and redox biology in Asia, Europe, and America.

Zusammenfassung
Focuses on the Phase II enzymes of drug metabolism (xenobiotics), which has important ramifications for endogenous metabolism and nutrition. This volume presents the knowledge and methodology on glucuronidation, sulfation, acetylation, and transport systems in this field of research. It also includes aspects on Phase III, transport systems.

Inhalt
1 UDP-glucuronosyltransferases: Gene structures of the UGT1 and UGT2 families; 2
Identification and characterization of functional hepatocyte nuclear factor 1 binding sites in UDP-Glucuronosytransferase genes; 3 Substrate Specificity of Human Hepatic UDP-Glucuronosyltransferaes; 4 UDP-glucuronosytransferase (UGT) 1A6: structural, functional and regulatory aspects; 5 The Role of Ah Receptor in Induction of Human UDP-glucuronosyltransferase 1A1; 6 Regulation of the human UGT1A1 gene by nuclear receptors CAR, PXR and GR; 7 Isoform-selective probe substrates for in vitro studies of human UDP-glucuronosyltransferases; 8 Structure of UDP-glucuronosyltransferases in membranes; 9 Human SULT1A genes: Cloning and activity assays of the SULT1A promoters; 10 Vitamin D Receptor Regulation of the Steroid/Bile Acid Sulfotransferase SULT2A1; 11 Screening and characterizing human NAT2 variant; 12 Inactivation of human arylamine N-acetyltransferase 1 by hydrogen peroxide and peroxinitrite; 13 SULT and NAT in Mutagenicity Testing: Technical Aspects; 14 A comparative molecular field analysis (CoMFA) based approach to prediction of sulfotransferase catalytic specificity; 15 Glucuronidase deconjugation in inflammation; 16 Three-dimensional structures of sulfatases; 17 Estrogen sulfatase; 18 Analysis for localization of steroid sulfatase in human tissues; 19 Metabolism of Phytoestrogen Conjugates; 20 Coenzyme Q and phenolic conjugate metabolism; 21 Synthesis of bile acid CoA thioesters in the amino acid conjugation of bile acids; 22 Bile acid CoA: amino acid N-acyltransferase in the amino acid conjugation of bile acids; 23 Multidrug resistance protein 1-mediated export of glutathione and glutathione disulphide from brain astrocytes; 24 The genetics of ATP-binding cassette transporters; 25 Functional analysis of detergent-solubilized and membrane-reconstituted ABC Transporters; 26 Yeast ABC transporters - Cellular cleaning pumps; 27 High-speed screening of human ABC transporter function and genetic polymorphisms: New strategies in pharmacogenomics; 28 Coordinate transcriptional regulation of transport and metabolism; 29 Uptake and efflux transporters for anionic conjugates in human Hepatocytes; 30 Biliary canalicular transport systems: short-term regulation; 31 Inborn errors of biliary canalicular transport systems; 32 Epoxide Hydrolases - Structure, function, mechanism and assay; 33 Pregnane X receptor-mediated transcription; 34 Animal models of xenobiotic receptors in drug metabolism and diseases; 35 Cancer and molecular biomarkers of Phase 2

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