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Cancer therapeutics has seen an emergence and re-emergence of two metabolic fields in recent years, namely bioactive sphingolipids and glycolytic metabolism. Anaerobic glycolysis and its role in cancer has been recognized in cancer biology over 90 years. In recent decades, the role of sphingolipids in cancer cell metabolism has gained recognition, notably ceramide's essential role in programmed cell death and the role of the glucosylceramide synthase (GCS) in chemotherapeutic resistance. Despite this knowledge, a direct link between these two fields has yet to be concretely drawn. Herein, we show that in a model of highly glycolytic cells, generation of the glycosphingolipid (GSL) glucosylceramide (GlcCer) by GCS was elevated in response to increased glucose availability, while glucose deprivation diminished GSL levels. This effect was likely substrate dependent, independent of both GCS levels and activity. Conversely, leukemia cells with elevated GSLs showed a significant change in GCS activity, but no change in glucose uptake or GCS expression. In a leukemia cell line with elevated GlcCer, treatment with inhibitors of glycolysis or the pentose phosphate pathway significantly decreased GlcCer levels. When combined with pre-clinical inhibitor ABT-263, this effect was augmented and production of proapoptotic sphingolipid ceramide increased. Taken together, we have shown that there exists a definitive link between glucose metabolism and GSL production, laying the groundwork for connecting two distinct yet essential metabolic fields in cancer research. Furthermore, we have proposed a novel combination therapeutic option targeting two metabolic vulnerabilities for the treatment of leukemia.
This book provides the first comprehensive coverage of the quickly evolving research field of membrane contact sites (MCS). A total of 16 chapters explain their organization and role and unveil the significance of MCS for various diseases. MCS, the intracellular structures where organellar membranes come in close contact with one another, mediate the exchange of proteins, lipids, and ions. Via these functions, MCS are critical for the survival and the growth of the cell. Owing to that central role in the functioning of cells, MCS dysfunctions lead to important defects of human physiology, influence viral and bacterial infection, and cause disease such as inflammation, type II diabetes, neurodegenerative disorders, and cancer. To approach such a multifaceted topic, this volume assembles a series of chapters dealing with the full array of research about MCS and their respective roles for diseases. Most chapters also introduce the history and the state of the art of MCS research, which will initiate discussion points for the respective types of MCS for years to come. This work will appeal to all cell biologists as well as researchers on diseases that are impacted by MCS dysfunction. Additionally, it will stimulate graduate students and postdocs who will energize, drive, and develop the research field in the near future.
Metabolism includes various pathways of chemical reactions; understanding these pathways leads to an improved knowledge of the causes, preventions, and cures for human diseases. Medical Biochemistry: Human Metabolism in Health and Disease provides a concise yet thorough explanation of human metabolism and its role in health and diseases. Focusing on the physiological context of human metabolism without extensive consideration of the mechanistic principles of underlying enzymology, the books serves as both a primary text and resource for students and professional in medical, dental, and allied health programs.
A review of childhood neurodegenerative and other progressive but non-degenerative disorders to guide their diagnosis and management.
Totally revised and expanded, the Color Atlas of Biochemistry presents the fundamentals of human and mammalian biochemistry on 215 stunning color plates.Alongside a short introduction to chemistry and the classical topics of biochemistry, the 2nd edition covers new approaches and aspects in biochemistry, such as links between chemical structure and biological function or pathways for information transfer, as well as recent developments and discoveries, such as the structures of many new important molecules. Key features of this title include:- The unique combination of highly effective color graphics and comprehensive figure legends;- Unified color-coding of atoms, coenzymes, chemical classes, and cell organelles that allows quick recognition of all involved systems;- Computer graphics provide simulated 3D representation of many important molecules.This Flexibook is ideal for students of medicine and biochemistry and a valuable source of reference for practitioners.
Rewritten and redesigned, this remains the one essential text on the diseases of skeletal muscle.
This third edition is a comprehensive and extended study about the best known approaches for preparing the main types of glycosides, covering the classic and more recent glycosylation reactions used for preparing simple and challenging glycosides currently used as potent antiviral and antineoplastic drugs, or fluorogenic substrates used for enzymatic detection in cell biology. Besides, this new edition provides more examples of the glycosidic methodologies followed for preparing complex glycoconjugates such as glycoproteins and glycosphingolipids and gangliosides used as adjuvants or as synthetic vaccines candidates. Also, additional mechanistic evidence is presented for better understanding of the glycosylation reaction, trying to identify the variables mainly depending on protecting and leaving groups, as well as catalyst and reaction condition which altogether directs the anomeric stereo control. A chapter on the glycoside hydrolysis is included in view of the increasing interest in the use of biomass as a natural and renewable source for obtaining important intermediates or products used in food or valuable materials. The author includes information in the characterization of glycosides section with the aim of giving additional tools for the structural assignment through NMR, X-Ray and mass spectra techniques.
Chemistry, Biochemistry, and Biology of 1-3 Beta Glucans and Related Polysaccharides presents a comprehensive, systematic and authoritative survey of information about a family of chemically related, but functionally diverse, naturally occurring polysaccharides--the (1-3)-glucans. International contributors describe the chemical and physicochemical properties of these glucans and their derivatives and the molecular biological and structural aspects of the enzymes involved in their formation and breakdown. A detailed analysis of their physiological roles in the various biological situations in which they are found will be provided. Additionally, evolutionary relationships among the family of these glucans will be described. Topics of medical relevance include detailing the glucans' interactions with the immune system and research for cancer therapy applications Web resource links allow scientists to explore additional beta glucan research Separate indexes divided into Species and Subject for enhanced searchability
Nutrient Metabolism defines the molecular fate of nutrients and other dietary compounds in humans, as well as outlining the molecular basis of processes supporting nutrition, such as chemical sensing and appetite control. It focuses on the presentation of nutritional biochemistry; and the reader is given a clear and specific perspective on the events that control utilization of dietary compounds. Slightly over 100 self-contained chapters cover all essential and important nutrients as well as many other dietary compounds with relevance for human health. An essential read for healthcare professionals and researchers in all areas of health and nutrition who want to access the wealth of nutrition knowledge available today in one single source. Key Features * Highly illustrated with relevant chemical structures and metabolic pathways * Foreword by Steven Zeisel, Editor-in-chief of the Journal of Nutritional Biochemistry * First comprehensive work on the subject
Liver disease in children is increasing in prevalence, placing a huge burden on healthcare systems and often requiring long-term management. Offering an integrative approach to the science and clinical practice of pediatric hepatology, this is the definitive reference text for improved diagnosis and treatment strategies. In the new edition of this authoritative text, chapters have been thoroughly revised in line with major advances in the field, such as recognizing the increased frequency of fatty liver disease, and how genetic testing has the potential to establish earlier diagnoses for a variety of diseases. Disorders covered include cholestasis, metabolic disorders and hepatitis, with their presentation across the spectrum of infancy, childhood and adolescence discussed. The indications and surgical aspects of liver transplant are explained and post-transplant care is described in detail. This is a valuable resource for pediatricians, hepatologists, gastroenterologists and all clinicians involved in the care of children with liver diseases.