In 1962, 30 years after the discovery by du Vigneaud have pathologic consequences. One potentially sig- of a new sulfur amino acid, homocysteine; Carson and nificant health outcome of such mild to moderate Neil reported two siblings with mental retardation in hyperhomocysteinemia is an increased risk of occlu- northern Ireland with elevated urinary homocystine. sive vascular disease. Homocysteine concentrations in Nearly simultaneously, Gerritsen and Waisman patients with vascular disease were, on average, 31 % greater than in normal controls. Prospective assess- identified increased homocystine in the urine of a mentally retarded infant in Wisconsin. Within two ment of vascular disease risk among men with higher years, Harvey Mudd, James Finkelstein, and their homocysteine concentrations indicated that plasma coworkers at the National Institutes of health (USA) homocysteine at only 12% above the upper limit of that the enzyme cystathionine ~- normal levels was associated with a 3. 4-fold increase had reported synthase was lacking in a liver biopsy specimen from in risk of acute myocardial infarction. Studies from another patient with homocystinuria. This was the original Framingham Heart Study cohort (USA) the first indication of a vitamin relationship to have shown strong, positive correlation between homocystinuria, because that enzyme has as its co- plasma homocysteine concentration and degree of factor vitamin B6 (pyridoxal phosphate). Thereafter, carotid stenosis.

Food research (and funding) is becoming more and more focused on health. While researchers and product developers have made great strides in food engineering, there needs to be increased focus on what happens when the food is actually digested. How is the food absorbed? Do the benefits remain? Digestion is a complex topic, and this will be the first book aimed at food researchers. Authored by a physiologist and a food engineer, the book willbe a welcome addition to the literature.

calcium exchanger, which is the topic of the final chapter of the book by N. Gabellini, A. Zatti, and E. Carafoli. Padova Zurich, Ernesto Carafoli February 2000 Joachim Krebs "Yes, calcium, that is everything ..." Contents Calcium Homeostasis and Its Evolution Robert J. P. Williams ...Evolution of EF-Hand Proteins Susumu Nakayama, Hiroshi Kawasaki and Robert Kretsinger...29 . Calmodulin Target Recognition: Common Mechanism and Structural Diversity Tao Yuan, Kyoko L. Yap and Mitsuhiko Ikura ...59 ...Calcium-Binding EGF-like Domains A. K. Downing, P. A. Handford and J. D. Campbell...83 ...Calmodulin-Dependent Protein Kinases Joachim Krebs...101 ...Structure of Calcineurin and Its Complex with Immunophilins Claude B. Klee ...125 ...2 The Ca + Pump of Sarcoplasmic and Endoplasmic Reticulum Membranes Giuseppe Inesi and Chikashi Toyoshima...143 ...2 The Plasma Membrane Ca + ATPase Danilo Guerini ...155 ...2 The Na+/Ca+ Exchanger: Structural Aspects, Function and Regulation Nadia Gabellini, Alessandra Zatti and Ernesto Carafoli ...173 ...Calcium Homeostasis and Its Evolution Robert J. P. Williams Inorganic Chemistry Laboratory, University of Oxford, South Parks Road, Oxford, OXl 3QR, UK E-mail: Susie. Compton@chem. ox. ac. uk The homeostasis of calcium is managed very differently in different organisms. A general outline of homeostasis, a dynamic balanced flow, is therefore described before a description of the systems in particular classes of organism. The organisms are treated in the sequence: prokaryotes, single-cell eukaryotes and, lastly, multicellular organisms reaching up to man.

Recent research, which Bone- Metabolic Function and Modulators expands on, has added new support to the idea that bone not only serves as a support system, but also functions as an integrating organ, with a significant regulatory role for lipid and energy metabolism. Links between physical activity and the skeleton are also becoming increasingly clear. This fully illustrated volume contains up-to-date information on the metabolic role of the skeleton and what this can mean for the treatment of metabolic as well as skeletal and auditory diseases. Bone- Metabolic Function and Modulators is of particular interest to clinician scientists, clinical and basic bone researchers, orthopedists, endocrinologists, internists, dentists, nurse practitioners, medical and dental residents and physiotherapists as well as students of the musculoskeletal system. Bone- Metabolic Function and Modulators is the seventh volume in the series Topics in Bone Biology, edited by Felix Bronner and Mary C. Farach-Carson. Other titles in this series:- Bone Formation Bone Resorption Engineering of Functional Skeletal Tissues Bone and Osteoarthritis Bone and Cancer Bone and Development Bone- Metabolic Function and Modulators is of particular interest to clinician scientists, clinical and basic bone researchers, orthopedists, endocrinologists, internists, dentists, nurse practitioners, medical and dental residents and physiotherapists as well as students of the musculoskeletal system. Bone- Metabolic Function and Modulators is the seventh volume in the series Topics in Bone Biology, edited by Felix Bronner and Mary C. Farach-Carson. Other titles in this series:- Bone Formation Bone Resorption Engineering of Functional Skeletal Tissues Bone and Osteoarthritis Bone and Cancer Bone and Development Bone- Metabolic Function and Modulators is of particular interest to clinician scientists, clinical and basic bone researchers, orthopedists, endocrinologists, internists, dentists, nurse practitioners, medical and dental residents and physiotherapists as well as students of the musculoskeletal system. Bone- Metabolic Function and Modulators is the seventh volume in the series Topics in Bone Biology, edited by Felix Bronner and Mary C. Farach-Carson. Other titles in this series:- Bone Formation Bone Resorption Engineering of Functional Skeletal Tissues Bone and Osteoarthritis Bone and Cancer Bone and Development

This text covers the basic principles of mitochondrial dynamics in cardiovascular medicine, with particular emphasis on their functional roles in physiology and disease. The book will include articles pertaining to mitochondrial fitness on a global basis, providing therefore an update on the progress made in several aspects in the field. Thus, it will assist scientists and clinicians alike in furthering basic and translational research. Organized in sections focusing on: basic science, mitochondrial dysfunction in cardiac disorders, in vascular disorders, in metabolic disorders, in kidney disease, therapeutic challenges and options, this essential volume fills imperative gaps in understanding and potentially treating several cardiovascular disorders.

This book discusses the maximal power and capacity of the three major biochemical pathways - aerobic (oxygen consumption), anaerobic lactic (muscle lactate accumulation in absence of oxygen consumption), and anaerobic alactic (phosphocreatine hydrolysis) metabolism - as well as the factors that limit them. It also discusses the metabolic and cardio-pulmonary mechanisms of the dynamic response to exercise. The way and extent to which the power and capacity of the three major energy metabolisms are affected under a number of different conditions, such as training, hypoxia and microgravity, are also described.

As discussed in this book, a large body of evidence indicates that selenium is a cancer chemopreventive agent. Further evidence points to a role of this element in reducing viral expression, in preventing heart disease, and other cardiovascular and muscle disorders, and in delaying the progression of AIDS in HIV infected patients. Selenium may also have a role in mammalian development, in male fertility, in immune function and in slowing the aging process. The mechanism by which selenium exerts its beneficial effects on health may be through selenium-containing proteins. Selenium is incorporated into protein as the amino acid selenocysteine. Selenocysteine utilizes a specific tRNA, a specific elongation factor, a specific set of signals, and the codeword, UGA, for its cotranslational insertion into protein. It is indeed the 21st naturally occurring amino acid to be incorporated into protein and marks the first and only expansion of the genetic code since the code was deciphered in the mid 1960s.

The role of oxidative stress in human disease has become an area of intense interest. Free radicals, a normal product of metabolism, exist in all aerobic cells in balance with biochemical antioxidants. Environmental stress increases the levels of free radicals drastically, thereby disturbing the equilibrium between free radical production and the antioxidant capability causing oxidative stress. Over the years, ROS has been implicated in the pathologies of various diseases like cancer, neurological disorder, cardiovascular diseases rheumatoid arthritis, diabetes etc. This book provides an in depth critical state-of-art reviews from established investigators on free radicals, ROS associated pathogenesis of human diseases, biomarkers of oxidative damage, antioxidants, phytonutrients and other related health concerns of modern society. The present book is aimed at graduate students, researchers in academia, industry and clinicians with the interest in redox biology. Special attention has been devoted to the topic of ROS signalling, oxidative stress induced human pathologies & antioxidative therapies. The book consists of four parts in specified topics based on the current literatures for the better understanding of the readers with respect to their subject-wise interests. The first section of the book provides an overview about the ROS production and their measuring tools and techniques followed by the mechanisms involved in the oxidative stress in the second section. The third section describes the involvement of oxidative stress in different human diseases and the last section focuses on the different strategies to ameliorate oxidative stress induced stress.

The most recent developments in research on hepatic encephalopathy, inborn hyperammonaemic syndromes and nitrogen metabolism, including clinical aspects, were presented by international acknowledged experts in this active research field at the 12th International Symposium on Hepatic Encephalopathy, which was held from June 1 to 4, 2005 in Solingen, Schloss Burg, Germany. This book comprehensively summarizes the most important novel issues on hepatic encephalopathy and nitrogen metabolism and is of interest not only for scientists in the field, but also for interested clinicians. This update of present knowledge will provide a platform for future research in the field of hepatic encephalopathy and nitrogen metabolism.

The nitrogen-containing ring structures are at the hub of metabolism and include ATP, nucleic acids, many coenzymes, metabolic regulators and integrators such as adenosine and GTP, signalling compounds such as cyclic nucleotides and plant cytokinins and biochemically functional pigmets of which haemoglobin, the cytochromes and chlorophyll are examples. This important book collates and integrates current knowledge of all the biologically important N-heterocyclic compounds, covering the relationship between their chemical structures and physiological functions within this key group of compounds. Few biochemical reaction sequences do not involve one of these compounds as a substrate, product or coenzyme and a full understanding of the interrelationship between their structure and function is vital for all those woorking in the field of biochemistry. Professor Eric Brown who has a huge wealth of experience in teaching and research on these compounds has written a very comprehensible and thorough book which will be of great value for advanced students and researchers in biochemistry and those at the interfacing subject areas of chemistry, biology and pharmacology including all those employed in researching biological function within pharmaceutical companies.

Research over the years has demonstrated that free radicals mediated oxidative stress lies at the helm of almost all patho-physiological phenomena. These findings emphasize on the need to understand the underlying molecular mechanism(s) and their critical role in the pathogenesis. This book aims to focus on these areas to provide readers a comprehensive outlook about the major redox sensitive pathways and networks involved in various disease conditions. In the first chapter of the book, basic information about the oxidative stress, its generation, its biomarkers and its role in body are discussed. In the next three chapters, the role of oxidative stress in various pathologies ranging from neurological disorders, to cardiovascular diseases, cancers, metabolic diseases and ageing have been described. Chapter 5 cumulatively describes the most important molecular signaling pathways that are affected by reactive oxygen species (ROS). These are the mechanisms which are common denominators in various pathological states. In the next part of the book, various antioxidant strategies to target and mitigate ROS have been discussed with details on the mechanisms. Selenium, being the research focus and interest of the authors for years, the role of selenium as an antioxidant as part of selenoproteins has been included in the book. Finally, the book culminates with authors' perspective on the future of the redox biology field. Throughout the book, efforts have been made to use simplified language and suitable figures for ease to understand the contents. Although the authors have tried to touch on all the different aspects of oxidative stress in detail, the fact that it is a continuously growing field with updates coming every day, there might be some areas which might not be described in depth. This book is designed for students, young scientists to get acquainted with the redox biology. Overall, this book is a reference to understand the redox regulation of cellular signaling pathways involved in pathogenesis.

Experienced physicians concisely explain the pathophysiology and clinical manifestations of endocrine disorders and survey all the latest laboratory diagnostics. Topics range widely from an overview of the diagnosis of diabetes and the long-term monitoring of its complications to the evaluation of menstrual dysfunction. Coverage is also given to the diagnosis of pituitary tumors, Cushing's syndrome, thyroid disease, and hypoglycemia; the evaluation of endocrine-induced hypertension; the assessment of dyslipidemia and obesity; and approaches to diagnosing hyper- and hypocalcemia. There are also discussions of osteoporosis, hypogonadism and erectile dysfunction, and hyperandrogenism in women. The authors each review the complex physiological basis of the relevant endocrine processes and provide richly instructive recommendations for followup and long-term management of patients.

Atherosclerosis leading to coronary heart disease and to cerebrovascular disorders is the number one cause of death in industrialized societies. For the last two decades, great ad vances have been made in understanding the pathogenesis of those disorders. Recent studies have revealed that the earliest event in atherogenesis is the adhesion of circulating leukocytes to the vascular endothelial cells and their migration into the subendothelial space. These cells are known to playa central role in the formation of a fatty streak consist ing of lipid-laden foam cells. As pathological events continue, the lesion is converted to a more fibrous lesion associated with vascular smooth muscle cells. To solve the enigma of this complicated process, intensive studies in molecular biology have disclosed the genes involved in those events. Some of the genes have been verified by creation of novel animal models, which have led to novel therapeutic strategies for subjects with atherosclerosis. This volume contains papers presented at the International Symposium on Lipoprotein Metabolism and Atherogenesis held in Kyoto December 5-8, 1998, supported in part by the Japan Intractable Diseases Research Foundation. The following three topics were the focus of the three-day program: I) The molecular approach to studying risk factors and prevention 2) The creation of novel animal models 3) Lipoprotein disorder as a cause of activation of vascular endothelial cells Thirty distinguished researchers from the United States, the United Kingdom, Austria, Finland, Australia, and Japan were invited.

This book discusses the relationship between cellular immunity and tryptophan metabolism, as well as its products, serotonin and melatonin, in the development of several diseases and reappraises the common signal transduction pathways of the neurodegenerative diseases, carcinogenesis, immune tolerance, inflammation, hypersensitivity reactions, neuropsychiatric disorders, in addition to bacterial tryptophan biosynthesis and novel antimicrobials. Tryptophan Metabolism: Implications for Biological Processes, Health and Disease presents fundamental information on tryptophan related metabolic pathways and metabolites, implications of these products for specific biological processes, diseases and conditions. This book focuses on effects of tryptophan metabolites on human health and will appeal to researchers, clinicians and students within this field.

Internationally eminent scientists illuminate the most important scientific aspects of essential fatty acids (EFAs)-from their biochemistry to their physiological consequences in both health and illness. The distinguished contributors integrate a wide range of topics, including the basic biochemistry of EFAs and lipid metabolism, the role of EFAs in the neuronal membrane, the effects of EFAs and lipids in various diseases, and the effects of normal levels and EFA deficiencies on cognition and behavior. The book's consolidation of our knowledge of the biology and metabolism of the EFAs lays the groundwork for dramatic advances in our understanding of these ubiquitous biochemicals and their role in health and illness.

Systems Metabolic Engineering is changing the way microbial cell factories are designed and optimized for industrial production.
Integrating systems biology and biotechnology with new concepts from synthetic biology enables the global analysis and engineering of microorganisms and bioprocesses at super efficiency and versatility otherwise not accessible. Without doubt, systems metabolic engineering is a major driver towards bio-based production of chemicals, materials and fuels from renewables and thus one of the core technologies of global green growth. In this book, Christoph Wittmann and Sang-Yup Lee have assembled the world leaders on systems metabolic engineering and cover the full story from genomes and networks via discovery and design to industrial implementation practises.
This book is a comprehensive resource for students and researchers from academia and industry interested in systems metabolic engineering. It provides us with the fundaments to targeted engineering of microbial cells for sustainable bio-production and stimulates those who are interested to enter this exiting research field.