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Carbonic Anhydrase: Mechanism, Regulation, Links to Disease, and Industrial Applications

Author: Susan C. Frost

Publisher: Springer Science & Business Media

Published: 2013-10-22

Total Pages: 429

ISBN-13: 9400773595

The study of carbonic anhydrase has spanned multiple generations of scientists. Carbonic anhydrase was first discovered in 1932 by Meldrum and Roughton. Inhibition by sulfanilamide was shown in 1940 by Mann and Keilin. Even Hans Krebs contributed to early studies with a paper in 1948 showing the relationship of 25 different sulfonamides to CA inhibition. It was he who pointed out the importance of both the charged and uncharged character of these compounds for physiological experiments. The field of study that focuses on carbonic anhydrase (CA) has exploded in recent years with the identification of new families and isoforms. The CAs are metalloenzymes which are comprised of 5 structurally different families: the alpha, beta, gamma, and delta, and epsilon classes. The alpha class is found primarily in animals with several isoforms associated with human disease. The beta CAs are expressed primarily in plants and are the most divergent. The gamma CAs are the most ancient. These are structurally related to the beta CAs, but have a mechanism more similar to the alpha CAs. The delta CAs are found in marine algae and diflagellates. The epsilon class is found in prokaryotes in which it is part of the carboxysome shell perhaps supplying RuBisCO with CO2 for carbon fixation. With the excitement surrounding the discovery of disease-related CAs, scientists have redoubled their efforts to better understand structure-function relationships, to design high affinity, isotype-specific inhibitors, and to delineate signaling systems that play regulatory roles over expression and activity. We have designed the book to cover basic information of mechanism, structure, and function of the CA families. The authors included in this book bring to light the newest data with regard to the role of CA in physiology and pathology, across phylums, and in unique environmental niches.

Carbonic Anhydrase as Drug Target

Author: Daumantas Matulis

Publisher: Springer

Published: 2019-05-21

Total Pages: 353

ISBN-13: 303012780X

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This book offers deep insights into the thermodynamics and molecular structures of the twelve catalytically active isoforms of human carbonic anhydrase (CA) with a particular focus on inhibitor binding for drug design. X-ray crystallographic structures in combination with enzyme kinetic testing provide information on the interaction of CAs and their inhibitors, knowledge which is crucial for rational drug design. CAs are zinc carrying enzymes that catalyse the reversible interconversion of carbon dioxide and bicarbonate and are involved in numerous cellular processes. They are therefore a common target for drugs. The suppression of CA activities through inhibitory compounds has found application for example in diuretics and in glaucoma therapy. In this book methods used to determine binding thermodynamics of inhibitory compounds (Isothermal titration calorimetry, Fluorescent thermal shift assay/differential scanning fluorimetry and others) will be compared in detail. Also types and chemical synthesis of CA inhibitors, the use of antibodies against CAs as well as inhibitor application in animals are discussed.

The Carbonic Anhydrases

Author: W.R. Chegwidden

Publisher: Birkhäuser

Published: 2013-11-11

Total Pages: 614

ISBN-13: 303488446X

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Carbonic anhydrase (CA) is a seemingly ubiquitous enzyme of profound physiological importance, which plays essential roles in respiration, acid-base homeostasis, bone resorption, calcification, photosynthesis, several biosynthetic pathways and a variety of processes involving ion, gas and fluid transfer. This enzyme, which is present in at least three gene families (a, ß, ?), has found favour as a model for the study of evolution of gene families and for site-directed mutagenesis in structure/function relationships, for protein folding and for transgenic and gene target studies. Since the early use of CA inhibitors as diuretics and in treating congestive heart failure, the enzyme has been target of considerable clinical attention. Much of this is now focused on endeavours to produce a new generation of such drugs for the effective treatment of glaucoma and other potential applications. Recent data, suggesting links between CA and various disease processes, including cancer, have stimulated further...

The Carbonic Anhydrases

Author: N.D. Carter

Publisher: Springer Science & Business Media

Published: 2013-06-29

Total Pages: 374

ISBN-13: 1489907505

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As we approach the twenty-first century the problems of industrialization are evident: we find there is a greenhouse effect, the ozone layer is being depleted, the rain is acidified, and there is a terrible problem of increasing C0 concentrations in the atmo 2 sphere. The carbonic anhydrases are a unique family of enzymes that solve these problems in the human body: they are responsible for converting C0 (a gas) to 2 HC0-, which is the biggest intracellular buffer, with a concomitant decrease in a 3 hydroxyl ion. Globally, the functions of the carbonic anhydrases in photosynthesis in rain forests and in the algae and plankton that cover our oceans indicate that they are also of utmost importance in the maintenance of the acid-base balance on our planet. Although the whole field of C0 metabolism is enormous and still rapidly 2 expanding, because of the research interests of the editors this book is mainly concerned with mammalian carbonic anhydrases. However, if the interested reader intends to purify carbonic anhydrases from nonmammalian sources, Dr. Cheg widden has provided the necessary information in Chapter 7. The carbonic anhydrases were first discovered in 1933; until1976 there were thought to be only two isozymes. Since then CA ill, IY, V, VI, and Vll have been discovered and well characterized. There is, of course, no reason to believe that we have found them all.

Carbonic Anhydrase

Author: Claudiu T. Supuran

Publisher: CRC Press

Published: 2004-05-27

Total Pages: 588

ISBN-13: 1134400152

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Carbonic Anhydrase: Its Inhibitors and Activators provides a state-of-the-art overview of the latest developments and challenges in carbonic anhydrase research. Authors describe the mechanisms of action of specific inhibitors in relation to physiological function, and present previously unpublished research on CA activators. Written by a team of in

The Carbonic Anhydrases: Current and Emerging Therapeutic Targets

Author: W. Richard Chegwidden

Publisher:

Published: 2021

Total Pages: 0

ISBN-13: 9783030795122

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This volume assembles and integrates the wealth of diverse information that is now accumulating in this burgeoning field. The existing and potential therapeutic applications of targeting CA cover a remarkably wide-range of diseases and disorders and have generated increasing and extensive interest in recent years. Its inter-disciplinary approach embraces both the most up-to-date therapeutic application of CA-targeting and the latest research data that will provide a platform for the development of novel applications. The interested audience comprises scientists and clinicians from many relevant disciplines within science and medicine.

Hepatotoxicity

Author: Hyman J. Zimmerman

Publisher: Lippincott Williams & Wilkins

Published: 1999

Total Pages: 848

ISBN-13: 9780781719520

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Written by the foremost authority in the field, this volume is a comprehensive review of the multifaceted phenomenon of hepatotoxicity. Dr. Zimmerman examines the interface between chemicals and the liver; the latest research in experimental hepatotoxicology; the hepatotoxic risks of household, industrial, and environmental chemicals; and the adverse effects of drugs on the liver. This thoroughly revised, updated Second Edition features a greatly expanded section on the wide variety of drugs that can cause liver injury. For quick reference, an appendix lists these medications and their associated hepatic injuries. Also included are in-depth discussions of drug metabolism and factors affecting susceptibility to liver injury.

Carbonic Anhydrases as Biocatalysts

Author: Claudiu T. Supuran

Publisher: Elsevier

Published: 2015-01-14

Total Pages: 398

ISBN-13: 0444632638

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Carbonic anhydrases (CAs, EC 4.2.1.1) are ubiquitous metalloenzymes, present throughout most living organisms and encoded by five evolutionarily unrelated gene families. The Carbonic Anhydrases as Biocatalysts: From Theory to Medical and Industrial Applications presents information on the growing interest in the study of this enzyme family and their applications to both medicine and biotechnology. Offers comprehensive coverage of the carbonic anhydrases enzyme family and their properties as biocatalysts Includes current applications of carbonic anhydrases in biotechnology on the basis of their catalytic efficiency, including new technologies for CO2 capture processes Identifies new targets for drug design studies Provides a selectivity profile for the different carbonic anhydrases and their related biomedical applications

Seldin and Giebisch's The Kidney

Author: Robert J. Alpern

Publisher: Elsevier

Published: 2007-10-10

Total Pages: 2928

ISBN-13: 0080559506

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A classic nephrology reference for over 20 years, Seldin & Giebisch’s The Kidney, is the acknowledged authority on renal physiology and pathophysiology. The fourth edition follows the changed focus of nephrology research to the study of how individual molecules work together to affect cellular and organ function, emphasizing the mechanisms of disease. With over 40 new chapters and over 1000 illustrations, this edition offers the most in-depth discussion anywhere of the physiologic and pathophysiologic processes of renal disease. Comprehensive, authoritative coverage progresses from molecular biology and cell physiology to clinical issues regarding renal function and dysfunction. If you research the development of normal renal function or the mechanisms underlying renal disease, Seldin & Giebisch’s The Kidney is your number one source for information. * Offers the most comprehensive coverage of fluid and electrolyte regulation and dysregulation in 51 completely revised chapters unlike Brenner & Rector's The Kidney which devotes only 7 chapters to this topic. * Includes 3 sections, 31 chapters, devoted to regulation and disorders of acid-base homeostasis, and epithelial and nonepithelial transport regulation. Brenner & Rector's only devotes 5 chapters to these topics. * Previous three editions edited by Donald Seldin and Gerhard Giebisch, world renowned names in nephrology. The title for the fourth edition has been changed to reflect their considerable work on previous editions and they have also written the forward for this edition. * Over 20 million adults over age 20 have chronic kidney disease with the number of people diagnosed doubling each decade making it America's ninth leading cause of death.

In-cell NMR Spectroscopy

Author: Yutaka Ito

Publisher: Royal Society of Chemistry

Published: 2019-12-09

Total Pages: 322

ISBN-13: 1839160934

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In-cell NMR spectroscopy is a relatively new field. Despite its short history, recent in-cell NMR-related publications in major journals indicate that this method is receiving significant general attention. This book provides the first informative work specifically focused on in-cell NMR. It details the historical background of in-cell NMR, host cells for in-cell NMR studies, methods for in-cell biological techniques and NMR spectroscopy, applications, and future perspectives. Researchers in biochemistry, biophysics, molecular biology, cell biology, structural biology as well as NMR analysts interested in biological applications will all find this book valuable reading.