The life of proteins starts and ends as amino acids. In addition to the primary function as protein building blocks, amino acids serve multiple other purposes to make a plant's life worth living. This is true especially for the amino acids of the glutamate family, namely glutamate (Glu), glutamine (Gln), proline (Pro) and arginine (Arg), as well as the product of Glu decarboxylation, ?-aminobutyric acid (GABA). Synthesis, accumulation, interconversion and degradation of these five compounds contribute in many ways to the regulation of plant development and to responses to environmental challenges. Glu and Gln hold key positions as entry points and master regulators of nitrogen metabolism in plants, and have a pivotal role in the regulatory interplay between carbon and nitrogen metabolism. Pro and GABA are among the best-studied compatible osmolytes that accumulate in response to water deficit, yet the full range of protective functions is still to be revealed. Arg, with its exceptionally high nitrogen-to-carbon ratio, has long been recognized as a major storage form of organic nitrogen. Most of the enzymes involved in metabolism of the amino acids of the glutamate family in plants have been identified or can be predicted according to similarity with animal or microbial homologues. However, for some of these enzymes the detailed biochemical properties still remain to be determined in order to understand activities in vivo. Additionally, uncertainties regarding the subcellular localization of proteins and especially the lack of knowledge about intracellular transport proteins leave significant gaps in our understanding of the metabolic network connecting Glu, Gln, Pro, GABA and Arg. While anabolic reactions are distributed between the cytosol and chloroplasts, catabolism of the amino acids of the glutamate family takes place in mitochondria and has been implicated in fueling energy-demanding physiological processes such as root elongation, recovery from stress, bolting and pollen tube elongation. Exceeding the metabolic functions, the amino acids of the glutamate family were recently identified as important signaling molecules in plants. Extracellular Glu, GABA and a range of other metabolites trigger responses in plant cells that resemble the actions of Glu and GABA as neurotransmitters in animals. Plant homologues of the Glu-gated ion channels from mammals and protein kinase signaling cascades have been implicated in these responses. Pollen tube growth and guidance depend on GABA signaling and the root architecture is specifically regulated by Glu. GABA and Pro signaling or metabolism were shown to contribute to the orchestration of defense and programmed cell death in response to pathogen attacks. Pro signaling was additionally proposed to regulate developmental processes and especially sexual reproduction. Arg is tightly linked to nitric oxide (NO) production and signaling in plants, although Arg-dependent NO-synthases could still not be identified. Potentially Arg-derived polyamines constitute the missing link between Arg and NO signaling in response to stress. Taken together, the amino acids of the glutamate family emerge as important signaling molecules that orchestrate plant growth and development by integrating the metabolic status of the plant with environmental signals, especially in stressful conditions. This research topic collects contributions from different facets of glutamate family amino acid signaling or metabolism to bring together, and integrate in a comprehensive view the latest advances in our understanding of the multiple functions of Glu-derived amino acids in plants.

The life of proteins starts and ends as amino acids. In addition to the primary function as protein building blocks, amino acids serve multiple other purposes to make a plant's life worth living. This is true especially for the amino acids of the glutamate family, namely glutamate (Glu), glutamine (Gln), proline (Pro) and arginine (Arg), as well as the product of Glu decarboxylation, ?-aminobutyric acid (GABA). Synthesis, accumulation, interconversion and degradation of these five compounds contribute in many ways to the regulation of plant development and to responses to environmental challenges. Glu and Gln hold key positions as entry points and master regulators of nitrogen metabolism in plants, and have a pivotal role in the regulatory interplay between carbon and nitrogen metabolism. Pro and GABA are among the best-studied compatible osmolytes that accumulate in response to water deficit, yet the full range of protective functions is still to be revealed. Arg, with its exceptionally high nitrogen-to-carbon ratio, has long been recognized as a major storage form of organic nitrogen. Most of the enzymes involved in metabolism of the amino acids of the glutamate family in plants have been identified or can be predicted according to similarity with animal or microbial homologues. However, for some of these enzymes the detailed biochemical properties still remain to be determined in order to understand activities in vivo. Additionally, uncertainties regarding the subcellular localization of proteins and especially the lack of knowledge about intracellular transport proteins leave significant gaps in our understanding of the metabolic network connecting Glu, Gln, Pro, GABA and Arg. While anabolic reactions are distributed between the cytosol and chloroplasts, catabolism of the amino acids of the glutamate family takes place in mitochondria and has been implicated in fueling energy-demanding physiological processes such as root elongation, recovery from stress, bolting and pollen tube elongation. Exceeding the metabolic functions, the amino acids of the glutamate family were recently identified as important signaling molecules in plants. Extracellular Glu, GABA and a range of other metabolites trigger responses in plant cells that resemble the actions of Glu and GABA as neurotransmitters in animals. Plant homologues of the Glu-gated ion channels from mammals and protein kinase signaling cascades have been implicated in these responses. Pollen tube growth and guidance depend on GABA signaling and the root architecture is specifically regulated by Glu. GABA and Pro signaling or metabolism were shown to contribute to the orchestration of defense and programmed cell death in response to pathogen attacks. Pro signaling was additionally proposed to regulate developmental processes and especially sexual reproduction. Arg is tightly linked to nitric oxide (NO) production and signaling in plants, although Arg-dependent NO-synthases could still not be identified. Potentially Arg-derived polyamines constitute the missing link between Arg and NO signaling in response to stress. Taken together, the amino acids of the glutamate family emerge as important signaling molecules that orchestrate plant growth and development by integrating the metabolic status of the plant with environmental signals, especially in stressful conditions. This research topic collects contributions from different facets of glutamate family amino acid signaling or metabolism to bring together, and integrate in a comprehensive view the latest advances in our understanding of the multiple functions of Glu-derived amino acids in plants.

Genetic alterations in cancer, in addition to being the fundamental drivers of tumorigenesis, can give rise to a variety of metabolic adaptations that allow cancer cells to survive and proliferate in diverse tumor microenvironments. This metabolic flexibility is different from normal cellular metabolic processes and leads to heterogeneity in cancer metabolism within the same cancer type or even within the same tumor. In this book, we delve into the complexity and diversity of cancer metabolism, and highlight how understanding the heterogeneity of cancer metabolism is fundamental to the development of effective metabolism-based therapeutic strategies. Deciphering how cancer cells utilize various nutrient resources will enable clinicians and researchers to pair specific chemotherapeutic agents with patients who are most likely to respond with positive outcomes, allowing for more cost-effective and personalized cancer therapeutic strategies.

This manual deals specifically with laboratory approaches to diagnosing inborn errors of metabolism. The key feature is that each chapter is sufficiently detailed so that any individual can adopt the described method into their own respective laboratory.

Glutamate is the most pervasive neurotransmitter in the central nervous system (CNS). Despite this fact, no validated biological markers, or biomarkers, currently exist for measuring glutamate pathology in CNS disorders or injuries. Glutamate dysfunction has been associated with an extensive range of nervous system diseases and disorders. Problems with how the neurotransmitter glutamate functions in the brain have been linked to a wide variety of disorders, including schizophrenia, Alzheimer's, substance abuse, and traumatic brain injury. These conditions are widespread, affecting a large portion of the United States population, and remain difficult to treat. Efforts to understand, treat, and prevent glutamate-related disorders can be aided by the identification of valid biomarkers. The Institute of Medicine's Forum on Neuroscience and Nervous System Disorders held a workshop on June 21-22, 2010, to explore ways to accelerate the development, validation, and implementation of such biomarkers. Glutamate-Related Biomarkers in Drug Development for Disorders of the Nervous System: Workshop Summary investigates promising current and emerging technologies, and outlines strategies to procure resources and tools to advance drug development for associated nervous system disorders. Moreover, this report highlights presentations by expert panelists, and the open panel discussions that occurred during the workshop.

Fundamental biochemical studies of basic brain metabolism focusing on the neuroactive amino acids glutamate and GABA combined with the seminal observation that one of the key enzymes, glutamine synthetase is localized in astroglial cells but not in neurons resulted in the formulation of the term “The Glutamate-Glutamine Cycle.” In this cycle glutamate released from neurons is taken up by surrounding astrocytes, amidated by the action of glutamine synthetase to glutamine which can be transferred back to the neurons. The conversion of glutamate to glutamine is like a stealth technology, hiding the glutamate molecule which would be highly toxic to neurons due to its excitotoxic action. This series of reactions require the concerted and precise interaction of a number of enzymes and plasma membrane transporters, and this volume provides in-depth descriptions of these processes. Obviously such a series of complicated reactions may well be prone to malfunction and therefore neurological diseases are likely to be associated with such malfunction of the enzymes and transporters involved in the cycle. These aspects are also discussed in several chapters of the book. A number of leading experts in neuroscience including intermediary metabolism, enzymology and transporter physiology have contributed to this book which provides comprehensive discussions of these different aspects of the functional importance of the glutamate-glutamine cycle coupling homeostasis of glutamatergic, excitatory neurotransmission to basic aspects of brain energy metabolism. This book will be of particular importance for students as well as professionals interested in these fundamental processes involved in brain function and dysfunction.