The ABC Transporters of Human Physiology and Disease


Book Description

ATP Binding Cassette (ABC) transporters are a family of integral membrane proteins present in all cells of all species of archaea, eubacteria and eukaryota. The vast majority of these proteins control the transport across cellular membranes of molecules ranging from small ions to drugs, lipids and proteins. The human genome encodes 48 ABC transporter genes and mutations in most have been linked to disease. This book OCo that brings together state-of-the-art knowledge on ABC proteins in one volume OCo will provide students, professors and medical professionals with a background to the human ABC transporters that are known to be relevant to disease. Each of the 14 chapters is written by a leading researcher in the field. The genetics, structure and function of the proteins, and the future direction of research including the implications for human health are discussed in depth.




ABC Transporters in Human Disease


Book Description

The ATP-binding cassette (ABC) transporter genes are ubiquitous in the genomes of all vertebrates so far studied. The human ABC transporter superfamily contains 48 genes, subdivided into 7 subfamilies ranging from A to G (based on sequence homology of their nucleotide binding domains). The ABC proteins encoded by these genes are ATP-driven transmembrane pumps, some of which possess the capacity to efflux harmful toxic substances and therefore play a key role in xenobiotic defense. ABC proteins have been evolutionarily conserved from bacteria to humans and multiple gene duplication and deletion events in the ABC genes indicate that the process of gene evolution is still ongoing. Polymorphisms and variations in these genes are linked to variations in expression, function, drug disposition, and drug response. Single nucleotide polymorphisms (SNPs) in these genes could be markers of individual risk for adverse drug reactions or susceptibility to complex diseases. The pharmacogenetics of this unique family of transporters is still under study; however, in the context of human health, it is a well-known fact that variations in these transporters are the underlying cause for several human diseases including cystic fibrosis, Pseudoxanthoma elasticum (PXE), and X-linked adenoleukodystrophy (X-ALD).




Plant ABC Transporters


Book Description

This book is devoted to the fascinating superfamily of plant ATP-binding cassette (ABC) transporters and their variety of transported substrates. It highlights their exciting biological functions, covering aspects ranging from cellular detoxification, through development, to symbiosis and defense. Moreover, it also includes a number of chapters that center on ABC transporters from non-Arabidopsis species. ABC proteins are ubiquitous, membrane-intrinsic transporters that catalyze the primary (ATP-dependent) movement of their substrates through biological membranes. Initially identified as an essential aspect of a vacuolar detoxification process, genetic work in the last decade has revealed an unexpectedly diverse variety of ABC transporter substrates, which include not only xenobiotic conjugates, but also heavy metals, lipids, terpenoids, lignols, alkaloids and organic acids. The discovery that members of the ABCB and ABCG family are involved in the movement of phytohormones has further sparked their exploration and provided a new understanding of the whole family. Accordingly, the trafficking, regulation and structure-function of ABCB-type auxin transporters are especially emphasized in this book.




ABC Transporters - 40 Years on


Book Description

This book provides new structural, biochemical, and clinical information on ABC transporters. The authors explore and describe the state of the art of research, knowledge, and prospects for the future for this important family of proteins. The first ABC transporter was discovered in 1973 and was named P-glycoprotein. It elicits resistance to cytotoxic drugs, chiefly in human tumours, within which chemotherapy failure is observed in about 50% of cases. Together with its complex pharmacology, and even a suspected role in Alzheimer’s disease, this ABC transporter still eludes a clinical solution to its multidrug resistance property. ABC transporters are integral membrane active proteins and they belong to one of the largest protein families across all species. Their myriad roles encompass the import or export of a diverse range of allocrites, including ion, nutrients, peptides, polysaccharides, lipids, and xenobiotics. They are of major medical importance with many members elaborating multidrug resistance in bacteria, fungi, yeast, parasites, and humans. Other ABC transporters are involved in a number of inherited diseases, including cystic fibrosis, macular degeneration, gout, and several other metabolic disorders




The ABC Transporters of Human Physiology and Disease


Book Description

ATP Binding Cassette (ABC) transporters are a family of integral membrane proteins that are likely to be represented in all the cells of all species of archaea, eubacteria and eukaryota. The vast majority of these proteins control the transport of molecules (from small hydrophilic ions to lipids and proteins) across cellular membranes. The human genome encodes 48 ABC transporters and most have been shown to underlie one or more human diseases. This book that brings together state-of-the-art knowledge on proteins in one volume will provide students, professors and medical professionals with a background to the human ABC transporters that are known to be relevant to diseases. Each of the 14 chapters is written by a leading researcher in the field and includes contributions from Joe Bryan and Lydia Aguilar-Bryan, Kazu Ueda, Jack Riordan and Robert Tamp. The genetics, structure and function of the proteins, and the future direction of research including the implications for human health are discussed in depth.




ABC Proteins


Book Description

ABC Proteins is an in-depth, up-to-date analysis of all that is known about the subject to date. It discusses and compares evolution, biology and mechanism of action of all known ABC proteins, including the first structural studies as well as clinical implications. It will be useful to anyone trying to stay abreast of the latest findings. This book is sure to become a classic and will regularly be updated. Phylogeny and Evoloution of ABC Transporters Fundamental Aspects of the Mechanism of Action of ABC Transporters Prokaryote ABC Transporters Non-Mammalian Transporters Multidrug Transporters ABC Transporters, Physiological Roles and Human Disease Full color throughout




ABC Transporters in Human Diseases


Book Description

Mammalian ATP-binding cassette (ABC) transporters constitute a superfamily of proteins involved in many essential cellular processes. Most of these transporters are transmembrane proteins and allow the active transport of solutes, small molecules, and lipids across biological membranes. On the one hand, some of these transporters are involved in drug resistance (also referred to as MDR or multidrug resistance), a process known to be a major brake in most anticancer treatments, and the medical challenge is thus to specifically inhibit their function. On the other hand, molecular defects in some of these ABC transporters are correlated with several rare human diseases, the most well-documented of which being cystic fibrosis, which is caused by genetic variations in ABCC7/CFTR (cystic fibrosis transmembrane conductance regulator). In the latter case, the goal is to rescue the function of the deficient transporters using various means, such as targeted pharmacotherapies and cell or gene therapy. The aim of this Special Issue, "ABC Transporters in Human Diseases", is to present, through original articles and reviews, the state-of-the-art of our current knowledge about the role of ABC transporters in human diseases and the proposed therapeutic options based on studies ranging from cell and animal models to patients.




ABC Transporters: Biochemical, Cellular, and Molecular Aspects


Book Description

The critically acclaimed laboratory standard for more than forty years, Methods in Enzymology is one of the most highly respected publications in the field of biochemistry. Since 1955, each volume has been eagerly awaited, frequently consulted, and praised by researchers and reviewers alike. More than 285 volumes have been published (all of them still in print) and much of the material is relevant even today-truly an essential publication for researchersin all fields of life sciences. Prokaryotic ABC Transporters Eukaryotic ABC Transporters Nonmammalian ABC Transport Systems Mammalian P-Glycoproteins Multidrug Resistance Associated Protein Cystic Fibrosis Transmembrane Conductance Regulator Sulfonylurea Receptor Intracellular ABC Transporters




Encyclopedia of Molecular Pharmacology


Book Description

An essential text, this is a fully updated second edition of a classic, now in two volumes. It provides rapid access to information on molecular pharmacology for research scientists, clinicians and advanced students. With the A-Z format of over 2,000 entries, around 350 authors provide a complete reference to the area of molecular pharmacology. The book combines the knowledge of classic pharmacology with the more recent approach of the precise analysis of the molecular mechanisms by which drugs exert their effects. Short keyword entries define common acronyms, terms and phrases. In addition, detailed essays provide in-depth information on drugs, cellular processes, molecular targets, techniques, molecular mechanisms, and general principles.




The Liver


Book Description

Bridging the gap between basic scientific advances and the understanding of liver disease — the extensively revised new edition of the premier text in the field. The latest edition of The Liver: Biology and Pathobiology remains a definitive volume in the field of hepatology, relating advances in biomedical sciences and engineering to understanding of liver structure, function, and disease pathology and treatment. Contributions from leading researchers examine the cell biology of the liver, the pathobiology of liver disease, the liver’s growth, regeneration, metabolic functions, and more. Now in its sixth edition, this classic text has been exhaustively revised to reflect new discoveries in biology and their influence on diagnosing, managing, and preventing liver disease. Seventy new chapters — including substantial original sections on liver cancer and groundbreaking advances that will have significant impact on hepatology — provide comprehensive, fully up-to-date coverage of both the current state and future direction of hepatology. Topics include liver RNA structure and function, gene editing, single-cell and single-molecule genomic analyses, the molecular biology of hepatitis, drug interactions and engineered drug design, and liver disease mechanisms and therapies. Edited by globally-recognized experts in the field, this authoritative volume: Relates molecular physiology to understanding disease pathology and treatment Links the science and pathology of the liver to practical clinical applications Features 16 new “Horizons” chapters that explore new and emerging science and technology Includes plentiful full-color illustrations and figures The Liver: Biology and Pathobiology, Sixth Edition is an indispensable resource for practicing and trainee hepatologists, gastroenterologists, hepatobiliary and liver transplant surgeons, and researchers and scientists in areas including hepatology, cell and molecular biology, virology, and drug metabolism.