Special Issue "Role and Regulation of Glutamate Metabolism"
A special issue of Biomolecules (ISSN 2218-273X).
Deadline for manuscript submissions: closed (31 August 2015)
Prof. Dr. Kenneth E. Miller
Glutamate is a key amino acid related to intermediary metabolism in eukaryotic cells. A number of vertebrate tissues and organ systems, however, use glutamate and related amino acids, e.g., glutamine and aspartate, for specific functions. Neurons use glutamate as an excitatory neurotransmitter and as a precursor for the inhibitory neurotransmitter, gamma-amino butyric acid (GABA). Renal tubule cells regulate ammonia levels via glutamate production. Glutamate and glutamine are important amino acids for proper skeletal muscle function. Glutamate is influential in inflammatory activity of resident and recruited macrophages. Furthermore, many malignant cell phenotypes are dependent on glutamate metabolism for sustaining cell growth.
We invite submissions of research or review manuscripts related to the role and regulation of glutamate metabolism. Areas of interest include regulation of glutamate in specific tissue types, e.g., neuronal, glial, renal, muscle, immune, lung, intestinal, and tumor cells. These areas can include transcriptional and translational regulation of glutamate-related enzymes or transporters, intracellular signal modulation of glutamate metabolism, metabolic flux or allosteric modulation of glutamate synthesis, and the functional outcome of increased or diminished glutamate production. This issue will review recent findings and showcase original research in this diverse field.
We look forward to your contributions,
Prof. Dr. Kenneth E. Miller
Manuscript Submission Information
Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.
Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Biomolecules is an international peer-reviewed open access quarterly journal published by MDPI.
Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 650 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.
- glutamine synthetase
- glutamate dehydrogenase
- aspartate aminotransferase
- PRPP amidotransferase
- glutamate transport
- glutamine transport
The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.
Type of Paper: Review
Title: Computational Studies of Glutamate Transporters and Receptors
Authors: Serdar Kuyucak
Affiliation: School of Physics, University of Sydney, Sydney, New South Wales 2006, Australia;
Abstract: Glutamate is the major excitatory neurotransmitter in the human brain whose binding to receptors on neurons excites them while excess glutamate are removed from synapses via transporter proteins. Determination of the crystal structures of glutamate transporters and receptors has paved the way for computational investigation of their function at the molecular level. Here we review the molecular dynamics and free energy simulation methods used in these computational studies, and discuss the recent applications to glutamate transporters and receptors. The focus of the review is on the insights gained on the transport mechanism through computational methods, which otherwise is not directly accessible by experimental probes. Recent efforts to model the mammalian glutamate transporters, whose crystal structures have not been solved yet, are included in the review.
Type of Paper: Review
Title: Central Role of Glutamate Metabolism in the Maintenance of Nitrogen Homeostasis in Normal and Hyperammonemic Brain
Authors: Arthur J. L. Cooper and Thomas M. Jeitner
Affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla, NY 10595, USA;
E-Mail: email@example.com (A.J.L.C.); Thomas_Jeitner@nymc.edu (T.M.J.)
Abstract: Glutamate is present in the brain at an average concentration (typically 10-12 mM), far in excess of those of other amino acids. In glutamate-containing vesicles in the brain the concentration of glutamate may even exceed 100 mM. Yet because glutamate is a major excitatory neurotransmitter the concentration of this amino acid in the cerebral extracellular fluid must be kept low – typically µM. The remarkable gradient of glutamate in the different cerebral compartments (i.e., vesicles > cytosol/mitochondria > extracellular fluid) attests to the extraordinary effectiveness of glutamate transporters and the strict control of enzymes of glutamate synthesis and catabolism in well-defined cellular and subcellular compartments in the brain. Although the glutamate transporters are briefly discussed the major emphasis of the present review is on the enzymology contributing to the maintenance of glutamate levels under normal and hyperammonemic conditions. A major route for glutamate and ammonia removal is via the glutamine synthetase reaction. Glutamate is also removed by conversion to the inhibitory neurotransmitter GABA via the action of glutamate decarboxylase. On the other hand, cerebral glutamate levels are maintained by the action of glutaminase and by various α-ketoglutarate-linked aminotransferases (particularly aspartate aminotransferase and the mitochondrial and cytosolic forms of the branched-chain aminotransferases). Although the glutamate dehydrogenase reaction is freely reversible, owing to rapid removal of ammonia as glutamine, the direction of the glutamate dehydrogenase reaction in the brain in vivo is toward glutamate catabolism rather than toward the net synthesis of glutamate, even under hyperammonemia conditions. During hyperammonemia there is a large increase in cerebral glutamine content, but only small changes in the level of glutamate and α-ketoglutarate. In other words, hyperammonemia stimulates the net synthesis of 5-C units. This is accomplished by the ammonia-induced stimulation of the anaplerotic enzyme pyruvate carboxylase. Emphasis in this review will be on the central role of glutamate in the glutamate-glutamine and GABA-glutamine neurotransmitter cycles between neurons and astrocytes. Also discussed will be the recent finding of a “new” glutamate dehydrogenase isozyme in human brain and its possible relationship to neurodegenerative diseases.