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Special Issue "Glutamine: An Essential Non-Essential Amino Acid"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: 31 October 2020.

Special Issue Editor

Special Issue Information

Dear Colleagues,

Glutamine is a non-essential amino acid that is derived from glutamate via the action of the enzyme glutamine synthetase in most cells, and is the most common amino acid found in the blood. However, it is essential that this amino acid is present in rapidly dividing cells such as cells of the immune system and tumor cells, as the ability of these cells to synthesize glutamine is limited, and it effectively becomes an essential amino acid.

Glutamine can donate its carbon and nitrogen to ensure nucleotide, amino acid, and other macromolecule biosynthesis occurs in the cell. It can also be used as a source of cellular energy. Glutamine is a gluconeogenic substrate in the kidney, and can act as a non-toxic carrier of ammonia in body fluids.

This Special Issue of the International Journal of Molecular Sciences, “Glutamine: The Essential Non-Essential Amino Acid” will focus on the role glutamine plays in normal and transformed cells, be it catabolized to supply cellular energy or anabolized for the creation of key biomolecules in the cell. Of interest is the role that glutamine plays in the regulation of gene transcription and the changes that occur in the cell when they start to rely on this amino acid to supply many of their needs. The results from these studies will help us better understand the central role that this amino acid plays in cell and organ metabolism, and how disrupting its role in tumor cell biology may give rise to new therapeutic agents.

Dr. Terrence Piva
Guest Editor

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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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.

Keywords

  • glutamine
  • amino acids
  • mitochondria and TCA cycle
  • enzymes
  • nucleotide synthesis
  • cell and body metabolism
  • gene regulation
  • cellular transport
  • immune cell function
  • cell proliferation
  • transformed cells
  • enzyme inhibition

Published Papers (2 papers)

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Research

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Open AccessArticle
Causes and Consequences of A Glutamine Induced Normoxic HIF1 Activity for the Tumor Metabolism
Int. J. Mol. Sci. 2019, 20(19), 4742; https://doi.org/10.3390/ijms20194742 - 24 Sep 2019
Cited by 3
Abstract
The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of genes that are involved in metabolism under hypoxic conditions, but information regarding the transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated under normoxic and hypoxic [...] Read more.
The transcription factor hypoxia-inducible factor 1 (HIF1) is the crucial regulator of genes that are involved in metabolism under hypoxic conditions, but information regarding the transcriptional activity of HIF1 in normoxic metabolism is limited. Different tumor cells were treated under normoxic and hypoxic conditions with various drugs that affect cellular metabolism. HIF1α was silenced by siRNA in normoxic/hypoxic tumor cells, before RNA sequencing and bioinformatics analyses were performed while using the breast cancer cell line MDA-MB-231 as a model. Differentially expressed genes were further analyzed and validated by qPCR, while the activity of the metabolites was determined by enzyme assays. Under normoxic conditions, HIF1 activity was significantly increased by (i) glutamine metabolism, which was associated with the release of ammonium, and it was decreased by (ii) acetylation via acetyl CoA synthetase (ACSS2) or ATP citrate lyase (ACLY), respectively, and (iii) the presence of L-ascorbic acid, citrate, or acetyl-CoA. Interestingly, acetylsalicylic acid, ibuprofen, L-ascorbic acid, and citrate each significantly destabilized HIF1α only under normoxia. The results from the deep sequence analyses indicated that, in HIF1-siRNA silenced MDA-MB-231 cells, 231 genes under normoxia and 1384 genes under hypoxia were transcriptionally significant deregulated in a HIF1-dependent manner. Focusing on glycolysis genes, it was confirmed that HIF1 significantly regulated six normoxic and 16 hypoxic glycolysis-associated gene transcripts. However, the results from the targeted metabolome analyses revealed that HIF1 activity affected neither the consumption of glucose nor the release of ammonium or lactate; however, it significantly inhibited the release of the amino acid alanine. This study comprehensively investigated, for the first time, how normoxic HIF1 is stabilized, and it analyzed the possible function of normoxic HIF1 in the transcriptome and metabolic processes of tumor cells in a breast cancer cell model. Furthermore, these data imply that HIF1 compensates for the metabolic outcomes of glutaminolysis and, subsequently, the Warburg effect might be a direct consequence of the altered amino acid metabolism in tumor cells. Full article
(This article belongs to the Special Issue Glutamine: An Essential Non-Essential Amino Acid)
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Open AccessReview
The Role of Glutamine in the Complex Interaction between Gut Microbiota and Health: A Narrative Review
Int. J. Mol. Sci. 2019, 20(20), 5232; https://doi.org/10.3390/ijms20205232 - 22 Oct 2019
Cited by 5
Abstract
The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy [...] Read more.
The scientific literature has demonstrated that glutamine is one of the main beneficial amino acids. It plays an important role in gut microbiota and immunity. This paper provides a critical overview of experimental studies (in vitro, in vivo, and clinical) investigating the efficacy of glutamine and its effect on gut microbiota. As a result of this review, we have summarized that glutamine could affect gut microbiota via different mechanisms including the reduction in the ratio of Firmicutes to Bacteroidetes, with the activation of NF-κB and PI3K-Akt pathways, reducing the intestinal colonization (Eimeria lesions) and bacterial overgrowth or bacterial translocation, increasing the production of secretory immunoglobulin A (SIgA) and immunoglobulin A+ (IgA+) cells in the intestinal lumen, and decreasing asparagine levels. The potential applications of glutamine on gut microbiota include, but are not limited to, the management of obesity, bacterial translocation and community, cytokines profiles, and the management of side effects during post-chemotherapy and constipation periods. Further studies and reviews are needed regarding the effects of glutamine supplementation on other conditions in humans. Full article
(This article belongs to the Special Issue Glutamine: An Essential Non-Essential Amino Acid)
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