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Offers a review of developments along with tried and tested methods for isolation, resolution and quantification of inositol phospholipids and inositol polyphosphates in both cells and tissues. This book includes detailed methodology for identification of molecular species of inositol phospholipids, including their phosphates and glycans.
This book offers a wide ranging and review of cutting edge developments along with tried and tested methods for isolation, resolution and quantification of inositol phospholipids and inositol polyphosphates in both cells and tissues. It includes detailed and rigorous methodology for identification of molecular species of inositol phospholipids, including their phosphates and glycans, with numerous examples of specific applications. Wherever available, both chromatographic and mass spectrometric evidence is presented for specific phospholipid involvement in the biochemical transformations accompanying metabolic signalling events and, where possible, controversies have been resolved on basis of analytical ambiguity. The review of the lipid analyses extends to products of phosphatidylinositol kinases, phosphatases and lipases. A general review chapter is included on metabolic signalling with special emphasis on the lipid products of 3-kinases. In view of the general lack of commercially available standards for inositol phospholipids and inositol phosphates, the book concludes with a chapter on the preparation and collection of chromatographic and mass spectrometric proof of their purity and identity. This book complements recent books and reviews on the mechanisms metabolic signalling, receptor binding and the polypeptide structure of the proteins involved in the various signalling pathways. It also complements those texts that deal exclusively with the chemical synthesis of the phosphatidylinositols and their polyphosphates and glycans.
Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume I untangles the web of these enzymes and their products, and relates them to function in health and disease. Phosphoinositide 3-kinases and 3-phosphatases have received a special focus in volume I, and recent therapeutic developments in human disease are presented along with a historical perspective illustrating the impressive progress in the field.
This text introduces the basic methodological tools to measure inositol lipids and phosphates and also describes new approaches that have become available in the last ten years, including g RNA-silencing and the protocols involving inositol pyrophosphates.
`The heterogeneity of topics ... is very ambitious, and the result is, overall, successful because of the high quality of the individual contributions ... highly recommended.' -American Scientist, from a review of a previous volume Volume 26 examines the emerging areas of signal transduction based on myoinositol phosphates and Ca2+ while focusing on plant and animal responses. Chapters explore synthesis, separation, and identification of different inositol phosphates.
An understanding of the mechanisms by which plants perceive environmental cues, both physical and chemical, and transduce the signals that influence specific expression of genes, is an area of intensive scientific research. With the completion of the genome sequence of Arabidopsis it is understood now that a larger number of genes encode for proteins involved in signalling cascades and transcription factors. In this volume, different chapters deal with plant receptors, second messengers like calcium ions, phosphoinositides, salicylic acid and nitrous oxide, calcium binding proteins and kinases. In addition to dealing with the response of plants to light, hormones, pathogens, heat, etc. on cellular activity, work currently going on in apoptosis, cell division, and plastid gene expression is also covered in this book.
Phosphoinositides play a major role in cellular signaling and membrane organization. During the last three decades we have learned that enzymes turning over phosphoinositides control vital physiological processes and are involved in the initiation and progression of cancer, inflammation, neurodegenerative, cardiovascular, metabolic disease and more. In two volumes, this book elucidates the crucial mechanisms that control the dynamics of phosphoinositide conversion. Starting out from phosphatidylinositol, a chain of lipid kinases collaborates to generate the oncogenic lipid phosphatidylinositol(3,4,5)-trisphosphate. For every phosphate group added, there are specific lipid kinases – and phosphatases to remove it. Additionally, phospholipases can cleave off the inositol head group and generate poly-phosphoinositols, which act as soluble signals in the cytosol. Volume II extends into the role of phosphoinositides in membrane organization and vesicular traffic. Endocytosis and exocytosis are modulated by phosphoinositides, which determine the fate and activity of integral membrane proteins. Phosphatidylinositol(4,5)-bisphosphate is a prominent flag in the plasma membrane, while phosphatidylinositol-3-phosphate decorates early endosomes. The Golgi apparatus is rich in phosphatidylinositol-4-phosphate, stressed cells increase phosphatidylinositol(3,5)-bisphosphate, and the nucleus has a phosphoinositide metabolism of its own. Phosphoinositide-dependent signaling cascades and the spatial organization of distinct phosphoinositide species are required in organelle function, fission and fusion, membrane channel regulation, cytoskeletal rearrangements, adhesion processes, and thus orchestrate complex cellular responses including growth, proliferation, differentiation, cell motility, and cell polarization.
Lipids are the most abundant organic compounds found in the brain, accounting for up to 50% of its dry weight. The brain lipidome includes several thousands of distinct biochemical structures whose expression may greatly vary according to age, gender, brain region, cell type, as well as subcellular localization. In synaptic membranes, brain lipids specifically interact with neurotransmitter receptors and control their activity. Moreover, brain lipids play a key role in the generation and neurotoxicity of amyloidogenic proteins involved in the pathophysiology of neurological diseases. The aim of this book is to provide for the first time a comprehensive overview of brain lipid structures, and to explain the roles of these lipids in synaptic function, and in neurodegenerative diseases, including Alzheimer’s, Creutzfeldt-Jakob’s and Parkinson’s. To conclude the book, the authors present new ideas that can drive innovative therapeutic strategies based on the knowledge of the role of lipids in brain disorders. Written to provide a "hands-on" approach for readers Biochemical structures explained with molecular models, and molecular mechanisms explained with simple drawings Step-by-step guide to memorize and draw lipid structures Each chapter features a content summary, up-to-date references for additional study, and a key experiment with an explanation of the technique
The volumes in this authoritative series present a multidisciplinary approach to modeling and simulation of flows in the cardiovascular and ventilatory systems, especially multiscale modeling and coupled simulations. The cardiovascular and respiratory systems are tightly coupled, as their primary function is to supply oxygen to and remove carbon dioxide from the body's cells. Because physiological conduits have deformable and reactive walls, macroscopic flow behavior and prediction must be coupled to phenomenological models of nano- and microscopic events in a corrector scheme of regulated mechanisms when the vessel lumen caliber varies markedly. Therefore, investigation of flows of blood and air in physiological conduits requires an understanding of the biology, chemistry, and physics of these systems together with the mathematical tools to describe their functioning. Volume 4 is devoted to major sets of intracellular mediators that transmit signals upon stimulation of cell-surface receptors. Activation of signaling effectors triggers the release of substances stored in cellular organelles and/or gene transcription and protein synthesis. Complex stages of cell signaling can be studied using proper mathematical models, once the role of each component is carefully handled. Volume 4 also reviews various categories of cytosolic and/or nuclear mediators and illustrates some major signal transduction pathways, such as NFkappaB axis, oxygen sensing, and mechanotransduction.