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Metabolites
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Cellular Metabolism in the Omics Era
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Cellular Metabolism in the Omics Era

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Cell Metabolism".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 12363

Special Issue Editors

Dr. Greta Petrella

E-Mail Website
Guest Editor
Department of Chemical Sciences and Technologies, Università degli Studi di Roma Tor Vergata, 1, 00133 Rome, Italy
Interests: metabolomics; NMR; cellular metabolism; cancer; urinary biomarkers
Special Issues, Collections and Topics in MDPI journals
Dr. Daniel Oscar Cicero

E-Mail Website
Guest Editor
Department of Chemical Science and Technology, Università degli Studi di Roma Tor Vergata, 1, 00133 Rome, Italy
Interests: nuclear magnetic resonance; metabolomics; bladder cancer; cardiovascular diseases; metabolism and excercise
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The life of a cell is primarily based on a series of biochemical reactions that interconvert metabolites, which are turned on, turned off, accelerated, or slowed down according to the immediate needs of the cell. To regulate these processes, cells organize the reactions into various enzyme-catalyzed pathways, leading to the construction or destruction of cellular components that must be monitored and balanced in a coordinated manner, resulting in metabolism.

An organism’s biological processes and functions result from multiple interactions between tens of thousands of molecules. Moreover, understanding cellular metabolism occupies a crucial role in various scientific and clinical aspects.

The study of cell metabolism represents a junction between in vitro and in vivo experiments. Although cellular models simplify those mechanistic biological processes that can be reprogrammed within a complex organism, they are an intermediate and crucial step in getting in touch with understanding the biological events that occur in an entire body.

A cellular organism thrives on the fact that a multitude of metabolic pathways coexist simultaneously and are regulated in a concentrated manner. With the development of omics sciences, particularly metabolomics, the possibility has opened up to study how the levels of many metabolites vary correlatedly. In this context, metabolomics can be defined as an amplifier of a whole series of events that define characteristic phenotypes.

As Linus Pauling and Emil Zuckerkandl state, "life is a relationship among molecules and not a property of any one molecule."

Dr. Greta Petrella
Dr. Daniel Oscar Cicero
Guest Editors

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 submissions that pass pre-check are 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. Metabolites is an international peer-reviewed open access monthly 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 2700 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.

Keywords

  • cellular metabolism
  • omics sciences
  • metabolomics
  • metabolic networks
  • regulation
  • metabolic nodes
  • energy
  • homeostasis
  • signaling

Published Papers (6 papers)

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Research

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10 pages, 3080 KiB  
Article
Metabolic Modeling Identifies a Novel Molecular Type of Glioblastoma Associated with Good Prognosis
by Qiu Shen, Hua Yang, Qing-Peng Kong, Gong-Hua Li and Li Li
Metabolites 2023, 13(2), 172; https://doi.org/10.3390/metabo13020172 - 24 Jan 2023
Viewed by 1229
Abstract
Glioblastoma (GBM) is one of the most aggressive forms of cancer. Although IDH1 mutation indicates a good prognosis and a potential target for treatment, most GBMs are IDH1 wild-type. Identifying additional molecular markers would help to generate personalized therapies and improve patient outcomes. [...] Read more.
Glioblastoma (GBM) is one of the most aggressive forms of cancer. Although IDH1 mutation indicates a good prognosis and a potential target for treatment, most GBMs are IDH1 wild-type. Identifying additional molecular markers would help to generate personalized therapies and improve patient outcomes. Here, we used our recently developed metabolic modeling method (genome-wide precision metabolic modeling, GPMM) to investigate the metabolic profiles of GBM, aiming to identify additional novel molecular markers for this disease. We systematically analyzed the metabolic reaction profiles of 149 GBM samples lacking IDH1 mutation. Forty-eight reactions showing significant association with prognosis were identified. Further analysis indicated that the purine recycling, nucleotide interconversion, and folate metabolism pathways were the most robust modules related to prognosis. Considering the three pathways, we then identified the most significant GBM type for a better prognosis, namely N+P−. This type presented high nucleotide interconversion (N+) and low purine recycling (P−). N+P−-type exhibited a significantly better outcome (log-rank p = 4.7 × 10−7) than that of N−P+. GBM patients with the N+P−-type had a median survival time of 19.6 months and lived 65% longer than other GBM patients. Our results highlighted a novel molecular type of GBM, which showed relatively high frequency (26%) in GBM patients lacking the IDH1 mutation, and therefore exhibits potential in GBM prognostic assessment and personalized therapy. Full article
(This article belongs to the Special Issue Cellular Metabolism in the Omics Era)
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17 pages, 2294 KiB  
Article
Metabolic Reprogramming of Castration-Resistant Prostate Cancer Cells as a Response to Chemotherapy
by Greta Petrella, Francesca Corsi, Giorgia Ciufolini, Sveva Germini, Francesco Capradossi, Andrea Pelliccia, Francesco Torino, Lina Ghibelli and Daniel Oscar Cicero
Metabolites 2023, 13(1), 65; https://doi.org/10.3390/metabo13010065 - 31 Dec 2022
Cited by 6 | Viewed by 1946
Abstract
Prostate cancer at the castration-resistant stage (CRPC) is a leading cause of death among men due to resistance to anticancer treatments, including chemotherapy. We set up an in vitro model of therapy-induced cancer repopulation and acquired cell resistance (CRAC) on etoposide-treated CRPC PC3 [...] Read more.
Prostate cancer at the castration-resistant stage (CRPC) is a leading cause of death among men due to resistance to anticancer treatments, including chemotherapy. We set up an in vitro model of therapy-induced cancer repopulation and acquired cell resistance (CRAC) on etoposide-treated CRPC PC3 cells, witnessing therapy-induced epithelial-to-mesenchymal-transition (EMT) and chemoresistance among repopulating cells. Here, we explore the metabolic changes leading to chemo-induced CRAC, measuring the exchange rates cell/culture medium of 36 metabolites via Nuclear Magnetic Resonance spectroscopy. We studied the evolution of PC3 metabolism throughout recovery from etoposide, encompassing the degenerative, quiescent, and repopulating phases. We found that glycolysis is immediately shut off by etoposide, gradually recovering together with induction of EMT and repopulation. Instead, OXPHOS, already high in untreated PC3, is boosted by etoposide to decline afterward, though stably maintaining values higher than control. Notably, high levels of EMT, crucial in the acquisition of chemoresistance, coincide with a strong acceleration of metabolism, especially in the exchange of principal nutrients and their end products. These results provide novel information on the energy metabolism of cancer cells repopulating from cytotoxic drug treatment, paving the way for uncovering metabolic vulnerabilities to be possibly pharmacologically targeted and providing novel clinical options for CRPC. Full article
(This article belongs to the Special Issue Cellular Metabolism in the Omics Era)
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17 pages, 2509 KiB  
Article
Investigation of the Exometabolomic Profiles of Rat Islets of Langerhans Cultured in Microfluidic Biochip
by Amal Essaouiba, Rachid Jellali, Françoise Gilard, Bertrand Gakière, Teru Okitsu, Cécile Legallais, Yasuyuki Sakai and Eric Leclerc
Metabolites 2022, 12(12), 1270; https://doi.org/10.3390/metabo12121270 - 15 Dec 2022
Cited by 1 | Viewed by 1640
Abstract
Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic [...] Read more.
Diabetes mellitus (DM) is a complex disease with high prevalence of comorbidity and mortality. DM is predicted to reach more than 700 million people by 2045. In recent years, several advanced in vitro models and analytical tools were developed to investigate the pancreatic tissue response to pathological situations and identify therapeutic solutions. Of all the in vitro promising models, cell culture in microfluidic biochip allows the reproduction of in-vivo-like micro-environments. Here, we cultured rat islets of Langerhans using dynamic cultures in microfluidic biochips. The dynamic cultures were compared to static islets cultures in Petri. The islets’ exometabolomic signatures, with and without GLP1 and isradipine treatments, were characterized by GC-MS. Compared to Petri, biochip culture contributes to maintaining high secretions of insulin, C-peptide and glucagon. The exometabolomic profiling revealed 22 and 18 metabolites differentially expressed between Petri and biochip on Day 3 and 5. These metabolites illustrated the increase in lipid metabolism, the perturbation of the pentose phosphate pathway and the TCA cycle in biochip. After drug stimulations, the exometabolome of biochip culture appeared more perturbed than the Petri exometabolome. The GLP1 contributed to the increase in the levels of glycolysis, pentose phosphate and glutathione pathways intermediates, whereas isradipine led to reduced levels of lipids and carbohydrates. Full article
(This article belongs to the Special Issue Cellular Metabolism in the Omics Era)
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19 pages, 2293 KiB  
Article
The Glycosyltransferase Pathway: An Integrated Analysis of the Cell Metabolome
by Yannick Audet-Delage, Michèle Rouleau, Lyne Villeneuve and Chantal Guillemette
Metabolites 2022, 12(10), 1006; https://doi.org/10.3390/metabo12101006 - 21 Oct 2022
Cited by 2 | Viewed by 1838
Abstract
Nucleotide sugar-dependent glycosyltransferases (UGTs) are critical to the homeostasis of endogenous metabolites and the detoxification of xenobiotics. Their impact on the cell metabolome remains unknown. Cellular metabolic changes resulting from human UGT expression were profiled by untargeted metabolomics. The abundant UGT1A1 and UGT2B7 [...] Read more.
Nucleotide sugar-dependent glycosyltransferases (UGTs) are critical to the homeostasis of endogenous metabolites and the detoxification of xenobiotics. Their impact on the cell metabolome remains unknown. Cellular metabolic changes resulting from human UGT expression were profiled by untargeted metabolomics. The abundant UGT1A1 and UGT2B7 were studied as UGT prototypes along with their alternative (alt.) splicing-derived isoforms displaying structural differences. Nineteen biochemical routes were modified, beyond known UGT substrates. Significant variations in glycolysis and pyrimidine pathways, and precursors of the co-substrate UDP-glucuronic acid were observed. Bioactive lipids such as arachidonic acid and endocannabinoids were highly enriched by up to 13.3-fold (p < 0.01) in cells expressing the canonical enzymes. Alt. UGT2B7 induced drastic and unique metabolic perturbations, including higher glucose (18-fold) levels and tricarboxylic acid cycle (TCA) cycle metabolites and abrogated the effects of the UGT2B7 canonical enzyme when co-expressed. UGT1A1 proteins promoted the accumulation of branched-chain amino acids (BCAA) and TCA metabolites upstream of the mitochondrial oxoglutarate dehydrogenase complex (OGDC). Alt. UGT1A1 exacerbated these changes, likely through its interaction with the OGDC component oxoglutarate dehydrogenase-like (OGDHL). This study expands the breadth of biochemical pathways associated with UGT expression and establishes extensive connectivity between UGT enzymes, alt. proteins and other metabolic processes. Full article
(This article belongs to the Special Issue Cellular Metabolism in the Omics Era)
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Review

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26 pages, 1714 KiB  
Review
The Role of Cellular Metabolism in Maintaining the Function of the Dentine-Pulp Complex: A Narrative Review
by Kacper Nijakowski, Martyna Ortarzewska, Jakub Jankowski, Anna Lehmann and Anna Surdacka
Metabolites 2023, 13(4), 520; https://doi.org/10.3390/metabo13040520 - 05 Apr 2023
Cited by 3 | Viewed by 2954
Abstract
The cellular metabolic processes ensure the physiological integrity of the dentine-pulp complex. Odontoblasts and odontoblast-like cells are responsible for the defence mechanisms in the form of tertiary dentine formation. In turn, the main defence reaction of the pulp is the development of inflammation, [...] Read more.
The cellular metabolic processes ensure the physiological integrity of the dentine-pulp complex. Odontoblasts and odontoblast-like cells are responsible for the defence mechanisms in the form of tertiary dentine formation. In turn, the main defence reaction of the pulp is the development of inflammation, during which the metabolic and signalling pathways of the cells are significantly altered. The selected dental procedures, such as orthodontic treatment, resin infiltration, resin restorations or dental bleaching, can impact the cellular metabolism in the dental pulp. Among systemic metabolic diseases, diabetes mellitus causes the most consequences for the cellular metabolism of the dentine-pulp complex. Similarly, ageing processes present a proven effect on the metabolic functioning of the odontoblasts and the pulp cells. In the literature, several potential metabolic mediators demonstrating anti-inflammatory properties on inflamed dental pulp are mentioned. Moreover, the pulp stem cells exhibit the regenerative potential essential for maintaining the function of the dentine-pulp complex. Full article
(This article belongs to the Special Issue Cellular Metabolism in the Omics Era)
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22 pages, 2970 KiB  
Review
Survey for Computer-Aided Tools and Databases in Metabolomics
by Bayan Hassan Banimfreg, Abdulrahim Shamayleh and Hussam Alshraideh
Metabolites 2022, 12(10), 1002; https://doi.org/10.3390/metabo12101002 - 21 Oct 2022
Cited by 6 | Viewed by 1952
Abstract
Metabolomics has advanced from innovation and functional genomics tools and is currently a basis in the big data-led precision medicine era. Metabolomics is promising in the pharmaceutical field and clinical research. However, due to the complexity and high throughput data generated from such [...] Read more.
Metabolomics has advanced from innovation and functional genomics tools and is currently a basis in the big data-led precision medicine era. Metabolomics is promising in the pharmaceutical field and clinical research. However, due to the complexity and high throughput data generated from such experiments, data mining and analysis are significant challenges for researchers in the field. Therefore, several efforts were made to develop a complete workflow that helps researchers analyze data. This paper introduces a review of the state-of-the-art computer-aided tools and databases in metabolomics established in recent years. The paper provides computational tools and resources based on functionality and accessibility and provides hyperlinks to web pages to download or use. This review aims to present the latest computer-aided tools, databases, and resources to the metabolomics community in one place. Full article
(This article belongs to the Special Issue Cellular Metabolism in the Omics Era)
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