Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0


Book Description

This book, "Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity", presents five papers on human cytochrome P450 (CYP) and P450 reductase, three reviews on the role of CYPs in humans and their use as biomarkers, six papers on CYPs in microorganisms, and one study on CYP in insects. The first paper reports the in silico modeling of human CYP3A4 access channels. The second uses structural methods to explain the mechanism-based inactivation of CYP3A4 by mibefradil, 6,7-dihydroxy-bergamottin, and azamulin. The third article compares electron transfer in CYP2C9 and CYP2C19 using structural and biochemical methods, and the fourth uses kinetic methods to study electron transfer to CYP2C8 allelic mutants. The fifth article characterizes electron transfer between the reductase and CYP using in silico and in vitro methods, focusing on the conformations of the reductase. Then, two reviews describe clinical implications in cardiology and oncology and the role of fatty acid metabolism in cardiology and skin diseases. The second review is on the potential use of circulating extracellular vesicles as biomarkers. Five papers analyze the CYPomes of diverse microorganisms: the Bacillus genus, Mycobacteria, the fungi Tremellomycetes, Cyanobacteria, and Streptomyces. The sixth focuses on a specific Mycobacterium CYP, CYP128, and its importance in M. tuberculosis. The subject of the last paper is CYP in Sogatella furcifera, a plant pest, and its resistance to the insecticide sulfoxaflor.




Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity 2.0


Book Description

This book, "Cytochromes P450: Drug Metabolism, Bioactivation and Biodiversity", presents five papers on human cytochrome P450 (CYP) and P450 reductase, three reviews on the role of CYPs in humans and their use as biomarkers, six papers on CYPs in microorganisms, and one study on CYP in insects. The first paper reports the in silico modeling of human CYP3A4 access channels. The second uses structural methods to explain the mechanism-based inactivation of CYP3A4 by mibefradil, 6,7-dihydroxy-bergamottin, and azamulin. The third article compares electron transfer in CYP2C9 and CYP2C19 using structural and biochemical methods, and the fourth uses kinetic methods to study electron transfer to CYP2C8 allelic mutants. The fifth article characterizes electron transfer between the reductase and CYP using in silico and in vitro methods, focusing on the conformations of the reductase. Then, two reviews describe clinical implications in cardiology and oncology and the role of fatty acid metabolism in cardiology and skin diseases. The second review is on the potential use of circulating extracellular vesicles as biomarkers. Five papers analyze the CYPomes of diverse microorganisms: the Bacillus genus, Mycobacteria, the fungi Tremellomycetes, Cyanobacteria, and Streptomyces. The sixth focuses on a specific Mycobacterium CYP, CYP128, and its importance in M. tuberculosis. The subject of the last paper is CYP in Sogatella furcifera, a plant pest, and its resistance to the insecticide sulfoxaflor.




ADME Processes in Pharmaceutical Sciences


Book Description

Absorption, Distribution, Metabolism and Excretion (ADME) processes and their relationship with the design of dosage forms and the success of pharmacotherapy form the basis of this upper level undergraduate/graduate textbook. As an introduction oriented to pharmacy students, it is also written for scientist from different fields outside of pharmaceutics. (e.g. material scientist, material engineers, medicinal chemists) who might be working in a positions in pharmaceutical companies or whose work might benefit from basic training in the ADME concepts and some biological background. Pedagogical features such as objectives, keywords, discussion questions, summaries and case studies add valuable teaching tools. This book will provide not only general knowledge on ADME processes but also an updated insight on some hot topics such as drug transporters, multi-drug resistance related to pharmacokinetic phenomena, last generation pharmaceutical carriers (nanopharmaceuticals), in vitro and in vivo bioequivalence studies, biopharmaceuticals, pharmacogenomics, drug-drug and food-drug interactions, and in silico and in vitro prediction of ADME properties. In comparison with other similar textbooks, around half of the volume would be focused on the relationship between expanding scientific fields and ADME processes. Each of these burgeoning fields has a separate chapter in the second part of the volume, and was written with leading experts on the correspondent topic, including scientists and academics from USA and UK (Duquesne University School of Pharmacy, Indiana University School of Medicine, University of Utah College of Pharmacy, University of Maryland, University of Bath). Additionally, each of the initial chapters dealing with the generalities of drug absorption, distribution, metabolism and excretion would include relevant, classic examples related to each topic with appropriate illustrations (e.g. importance of active absorption of levodopa, implications in levodopa administration, drug drug interactions and food drug interactions emerging from the active uptake; intoxication with paracetamol as a result of glutathione depletion, CYP induction and its relationship with acute liver failure caused by paracetamol, etc). ADME Processes and Pharmaceutical Sciences is written as a core textbook for ADME processes, pharmacy, pharmacokinetics, drug delivery, biopharmaceutics, drug disposition, drug design and medicinal chemistry courses.




Cytochrome P450 Protocols


Book Description

Cytochromes P450 (CYPs) comprise a large superfamily of proteins that are of central importance in the detoxification or activation of a tremendous number of natural and synthetic hydrophobic xenobiotics, including many therapeutic drugs, chemical carcinogens and environmental pollutants. CYPs are important in mediating interactions between an organism and its chemical environment and in the regulation of physiological processes. Cytochrome P450 Protocols, Third Edition focuses on high-throughput methods for the simultaneous analysis of multiple CYPs, substrates or ligands. Although the emphasis is on CYPs of mammalian origin, it reflects an increasing interest in CYPs of bacterial species. Also included are chapters on cytochrome P450 reductase (the redox partner of CYPs) and the flavin-containing monooxygenases (FMOs), and metabolomic and lipidomic approaches for identification of endogenous substrates of CYPs (‘de-orphanizing’ CYP substrates). Written in the successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Cytochrome P450 Protocols, Third Edition provides a wide range of techniques accessible to researchers in fields as diverse as biochemistry, molecular biology, pharmacology, toxicology, environmental biology and genetics.




Drug Metabolism


Book Description

Drug metabolism comprises the identification, characterization, and quantification of the chemicals or compounds produced in an animal or human upon administration of a drug. Research practices not only require the chemical structure but also aim to determine the pharmacological activities and/or toxicity of these compounds. This is first performed in animals, as studies attempt to identify and quantify metabolites, and later in humans, with care to further characterize metabolites that are either unique to or produced disproportionately in humans compared to animals. Characterization includes the determination of enzyme systems or other biological mechanisms that produce each identified metabolite; this information is used to predict potential drug-drug interactions with other compounds that increase or decrease metabolite formation and sources of biological variability in response or toxicity with varying patient genetics, which affect CYP isoform expression. This book's purpose is to provide some understanding of the biology and current technology applied in the field of drug metabolism.




Cytochrome P450


Book Description

Cytochrome P450: Structure, Mechanism, and Biochemistry, third edition is a revision of a review that summarizes the current state of research in the field of drug metabolism. The emphasis is on structure, mechanism, biochemistry, and regulation. Coverage is interdisciplinary, ranging from bioinorganic chemistry of cytochrome P450 to its relevance in human medicine. Each chapter provides an in-depth review of a given topic, but concentrates on advances of the last 10 years.




Human Pharmaceuticals, Hormones and Fragrances


Book Description

The observed concentrations of pharmaceuticals and personal care products (PPCPs) in raw wastewater confirm that municipal wastewater represents the main disposal pathway for the PPCPs consumed in households, hospitals and industry. In sewage treatment plant effluents most PPCPs are still present, since many of these polar and persistent compounds are being removed only partially or, in some cases, not at all. Treated wastewater therefore represents an important point source for PPCPs into the environment. After passing a sewage treatment plant the treated wastewater is mostly discharged into rivers and streams or sometimes used to irrigate fields. If drinking water is produced using resources containing a substantial proportion of treated wastewater (e.g. from river water downstream of communities) the water cycle is closed and indirect potable reuse occurs. Human Pharmaceuticals, Hormones and Fragrances provides an overview of the occurrence, analytics, removal and environmental risk of pharmaceuticals and personal care products in wastewater, surface water and drinking water. The book covers all aspects of the fate and removal of PPCPs in the whole water cycle: consumption and occurrence, analytical methods, the legal background, environmental risk assessment, human and animal toxicology, source control options, wastewater and drinking water treatment as well as indirect reuse. The book presents a summary of the results obtained during the EU project "Poseidon", combined with further expert knowledge on the field, and is written at a level appropriate for professionals involved in management of water resource quality. Professionals in the field including decision makers, engineers and scientists, as well as students entering the field, will find this an invaluable source of information. First comprehensive study on the assessment, fate and removal of pharmaceuticals and personal care products in wastewater and drinking water treatment. Emphasises the importance of micropollutants in the water cycle, provides methods for quantifying their fate and technologies for their removal.




Plant-derived Natural Products


Book Description

Plants produce a huge array of natural products (secondary metabolites). These compounds have important ecological functions, providing protection against attack by herbivores and microbes and serving as attractants for pollinators and seed-dispersing agents. They may also contribute to competition and invasiveness by suppressing the growth of neighboring plant species (a phenomenon known as allelopathy). Humans exploit natural products as sources of drugs, flavoring agents, fragrances and for a wide range of other applications. Rapid progress has been made in recent years in understanding natural product synthesis, regulation and function and the evolution of metabolic diversity. It is timely to bring this information together with contemporary advances in chemistry, plant biology, ecology, agronomy and human health to provide a comprehensive guide to plant-derived natural products. Plant-derived natural products: synthesis, function and application provides an informative and accessible overview of the different facets of the field, ranging from an introduction to the different classes of natural products through developments in natural product chemistry and biology to ecological interactions and the significance of plant-derived natural products for humans. In the final section of the book a series of chapters on new trends covers metabolic engineering, genome-wide approaches, the metabolic consequences of genetic modification, developments in traditional medicines and nutraceuticals, natural products as leads for drug discovery and novel non-food crops.




The Biological Activity of Phytochemicals


Book Description

This is the first volume to be published under a new series agreement for Recent Advances in Phytochemistry, co-published with the Phytochemical Society of North America.




Handbook of hair in health and disease


Book Description

Hair is a major component of the body's tissue system that contributes to the individual's make up and confers a large degree of personal identity. Apart from its visible façade, hair also has a functional role. It has an unique structure and complex molecular development. The very nature of hair makes it a suitable marker for the prognosis of disease. Hair can also be used to screen for toxins and changes in the diet. However, there are currently no suitable publications available that describe hair in a rational scientific context. This handbook provides an academic approach to hair in health and disease. Divided into five sections the Handbook of Hair in Health and Disease provides an insight into hair growth and loss, molecular and cellular biology of hair, dietary toxicity and pathological history, diseases and treatments of hair, as well as shampoos and conditioners. Unique features of each chapter in this volume include relevant and useful 'Key facts' which highlight interesting or important findings of the specific subjects and 'Summary points' that will give a clear overview of the subjects treated in each chapter. The Handbook of Hair in Health and Disease will be essential to a variety of users, such as trichologists, doctors and nurses and all those interested or working within the area of hair health. This includes nutritionists and dieticians, scientific beauticians, health workers and practitioners, college and university lecturers and undergraduate and graduate students.