Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
5.3
4.1
Journals
Metabolites
Special Issues
Metabolites and Signaling Pathways
share announcement

Metabolites and Signaling Pathways

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

Deadline for manuscript submissions: closed (31 October 2021) | Viewed by 34525

Special Issue Editor

Dr. Cholsoon Jang

E-Mail Website
Guest Editor
Department of Biological Chemistry, University of California, Irvine, CA 92697, USA
Interests: metabolomics; isotope tracing; nutrient metabolism; cancer metabolism

Special Issue Information

Dear Colleagues,

Metabolites have long been regarded as mere intermediates of the metabolic process. However, the recent surge of metabolism research has revealed metabolites as central players for regulating signaling proteins via gene expression and protein modifications to epigenetics. Conversely, signaling pathways also regulate metabolic enzymes at various steps, modulating the metabolism of cells. This Special Issue of Metabolites, “Metabolites and Signaling Pathways”, is dedicated to new discoveries regarding how metabolites and signaling pathways interact with each other. Topics will include but are not limited to metabolites that regulate signaling pathways and vice versa, development/application of new analytical or bioinformatics methods to discover metabolite-protein interactions or signaling metabolites, and other related issues.

Prof. Cholsoon Jang
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 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

  • metabolites
  • signaling pathways
  • metabolism
  • signaling molecules
  • enzyme regulation
  • allosteric regulators
  • epigenetics
  • gene expression

Published Papers (7 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

16 pages, 2497 KiB  
Article
Fructose Causes Liver Damage, Polyploidy, and Dysplasia in the Setting of Short Telomeres and p53 Loss
by Christopher Chronowski, Viktor Akhanov, Doug Chan, Andre Catic, Milton Finegold and Ergün Sahin
Metabolites 2021, 11(6), 394; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11060394 - 17 Jun 2021
Cited by 3 | Viewed by 2604
Abstract
Studies in humans and model systems have established an important role of short telomeres in predisposing to liver fibrosis through pathways that are incompletely understood. Recent studies have shown that telomere dysfunction impairs cellular metabolism, but whether and how these metabolic alterations contribute [...] Read more.
Studies in humans and model systems have established an important role of short telomeres in predisposing to liver fibrosis through pathways that are incompletely understood. Recent studies have shown that telomere dysfunction impairs cellular metabolism, but whether and how these metabolic alterations contribute to liver fibrosis is not well understood. Here, we investigated whether short telomeres change the hepatic response to metabolic stress induced by fructose, a sugar that is highly implicated in non-alcoholic fatty liver disease. We find that telomere shortening in telomerase knockout mice (TKO) imparts a pronounced susceptibility to fructose as reflected in the activation of p53, increased apoptosis, and senescence, despite lower hepatic fat accumulation in TKO mice compared to wild type mice with long telomeres. The decreased fat accumulation in TKO is mediated by p53 and deletion of p53 normalizes hepatic fat content but also causes polyploidy, polynuclearization, dysplasia, cell death, and liver damage. Together, these studies suggest that liver tissue with short telomers are highly susceptible to fructose and respond with p53 activation and liver damage that is further exacerbated when p53 is lost resulting in dysplastic changes. Full article
(This article belongs to the Special Issue Metabolites and Signaling Pathways)
►▼ Show Figures

Figure 1

21 pages, 8609 KiB  
Article
13C Metabolic Flux Analysis Indicates Endothelial Cells Attenuate Metabolic Perturbations by Modulating TCA Activity
by Bilal Moiz, Jonathan Garcia, Sarah Basehore, Angela Sun, Andrew Li, Surya Padmanabhan, Kaitlyn Albus, Cholsoon Jang, Ganesh Sriram and Alisa Morss Clyne
Metabolites 2021, 11(4), 226; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11040226 - 07 Apr 2021
Cited by 11 | Viewed by 3567
Abstract
Disrupted endothelial metabolism is linked to endothelial dysfunction and cardiovascular disease. Targeted metabolic inhibitors are potential therapeutics; however, their systemic impact on endothelial metabolism remains unknown. In this study, we combined stable isotope labeling with 13C metabolic flux analysis (13C [...] Read more.
Disrupted endothelial metabolism is linked to endothelial dysfunction and cardiovascular disease. Targeted metabolic inhibitors are potential therapeutics; however, their systemic impact on endothelial metabolism remains unknown. In this study, we combined stable isotope labeling with 13C metabolic flux analysis (13C MFA) to determine how targeted inhibition of the polyol (fidarestat), pentose phosphate (DHEA), and hexosamine biosynthetic (azaserine) pathways alters endothelial metabolism. Glucose, glutamine, and a four-carbon input to the malate shuttle were important carbon sources in the baseline human umbilical vein endothelial cell (HUVEC) 13C MFA model. We observed two to three times higher glutamine uptake in fidarestat and azaserine-treated cells. Fidarestat and DHEA-treated HUVEC showed decreased 13C enrichment of glycolytic and TCA metabolites and amino acids. Azaserine-treated HUVEC primarily showed 13C enrichment differences in UDP-GlcNAc. 13C MFA estimated decreased pentose phosphate pathway flux and increased TCA activity with reversed malate shuttle direction in fidarestat and DHEA-treated HUVEC. In contrast, 13C MFA estimated increases in both pentose phosphate pathway and TCA activity in azaserine-treated cells. These data show the potential importance of endothelial malate shuttle activity and suggest that inhibiting glycolytic side branch pathways can change the metabolic network, highlighting the need to study systemic metabolic therapeutic effects. Full article
(This article belongs to the Special Issue Metabolites and Signaling Pathways)
►▼ Show Figures

Figure 1

16 pages, 2614 KiB  
Article
Cholesterol Activates Cyclic AMP Signaling in Metaplastic Acinar Cells
by Francesca Grisan, Martina Spacci, Carlotta Paoli, Andrea Costamagna, Marco Fantuz, Miriam Martini, Konstantinos Lefkimmiatis and Alessandro Carrer
Metabolites 2021, 11(3), 141; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11030141 - 26 Feb 2021
Cited by 4 | Viewed by 10630
Abstract
Cholesterol is a non-essential metabolite that exerts both structural and signaling functions. However, cholesterol biosynthesis is elevated, and actively supports, pancreatic carcinogenesis. Our previous work showed that statins block the reprogramming of mutant KRAS-expressing acinar cells, that spontaneously undergo a metaplastic event termed [...] Read more.
Cholesterol is a non-essential metabolite that exerts both structural and signaling functions. However, cholesterol biosynthesis is elevated, and actively supports, pancreatic carcinogenesis. Our previous work showed that statins block the reprogramming of mutant KRAS-expressing acinar cells, that spontaneously undergo a metaplastic event termed acinar-to-ductal metaplasia (ADM) to initiate carcinogenesis. Here we tested the impact of cholesterol supplementation on isolated primary wild-type acinar cells and observed enhanced ductal transdifferentiation, associated with generation of the second messenger cyclic adenosine monophosphate (cAMP) and the induction of downstream protein kinase A (PKA). Inhibition of PKA suppresses cholesterol-induced ADM ex vivo. Live imaging using fluorescent biosensors dissected the temporal and spatial dynamics of PKA activation upon cholesterol addition and showed uneven activation both in the cytosol and on the outer mitochondrial membrane of primary pancreatic acinar cells. The ability of cholesterol to activate cAMP signaling is lost in tumor cells. Qualitative examination of multiple normal and transformed cell lines supports the notion that the cAMP/PKA axis plays different roles during multi-step pancreatic carcinogenesis. Collectively, our findings describe the impact of cholesterol availability on the cyclic AMP/PKA axis and plasticity of pancreatic acinar cells. Full article
(This article belongs to the Special Issue Metabolites and Signaling Pathways)
►▼ Show Figures

Figure 1

17 pages, 6906 KiB  
Article
An Integrated Metabolomics Study of Glucosinolate Metabolism in Different Brassicaceae Genera
by Yu Liu, Merja Rossi, Xu Liang, Hui Zhang, Li Zou and Choon Nam Ong
Metabolites 2020, 10(8), 313; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo10080313 - 31 Jul 2020
Cited by 17 | Viewed by 2952
Abstract
Glucosinolates are a group of plant secondary metabolites that can be hydrolyzed into a variety of breakdown products such as isothiocyanates, thiocyanates, and nitriles. These breakdown products can facilitate plant defense and function as attractants to natural enemies of insect pests. As part [...] Read more.
Glucosinolates are a group of plant secondary metabolites that can be hydrolyzed into a variety of breakdown products such as isothiocyanates, thiocyanates, and nitriles. These breakdown products can facilitate plant defense and function as attractants to natural enemies of insect pests. As part of the diet, some of these compounds have shown cancer-preventing activities, and the levels of these metabolites in the edible parts of the plants are of interest. In this study, we systematically examined variations in glucosinolates, their precursors, and their breakdown products in 12 commonly consumed vegetables of the Brassicaceae family with gas chromatography—quadrupole time-of-flight mass spectrometer (GC-Q-TOF/MS), liquid chromatography–quadrupole time-of-flight mass spectrometer (LC-Q-TOF/MS), and liquid chromatography—triple quadrupole mass spectrometer (LC-QQQ/MS), using both untargeted and targeted approaches. The findings were integrated with data from literature to provide a comprehensive map of pathways for biosynthesis of glucosinolates and isothiocyanates. The levels of precursor glucosinolates are found to correlate well with their downstream breakdown products. Further, the types and abundances of glucosinolates among different genera are significantly different, and these data allow the classification of plants based on morphological taxonomy. Further validation on three genera, which are grown underground, in damp soil, and above ground, suggests that each genus has its specific biosynthetic pathways and that there are variations in some common glucosinolate biosynthesis pathways. Our methods and results provide a good starting point for further investigations into specific aspects of glucosinolate metabolism in the Brassica vegetables. Full article
(This article belongs to the Special Issue Metabolites and Signaling Pathways)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

16 pages, 3614 KiB  
Review
Sensing and Signaling of Methionine Metabolism
by Linda Lauinger and Peter Kaiser
Metabolites 2021, 11(2), 83; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11020083 - 31 Jan 2021
Cited by 54 | Viewed by 6897
Abstract
Availability of the amino acid methionine shows remarkable effects on the physiology of individual cells and whole organisms. For example, most cancer cells, but not normal cells, are hyper dependent on high flux through metabolic pathways connected to methionine, and diets restricted for [...] Read more.
Availability of the amino acid methionine shows remarkable effects on the physiology of individual cells and whole organisms. For example, most cancer cells, but not normal cells, are hyper dependent on high flux through metabolic pathways connected to methionine, and diets restricted for methionine increase healthy lifespan in model organisms. Methionine’s impact on physiology goes beyond its role in initiation of translation and incorporation in proteins. Many of its metabolites have a major influence on cellular functions including epigenetic regulation, maintenance of redox balance, polyamine synthesis, and phospholipid homeostasis. As a central component of such essential pathways, cells require mechanisms to sense methionine availability. When methionine levels are low, cellular response programs induce transcriptional and signaling states to remodel metabolic programs and maintain methionine metabolism. In addition, an evolutionary conserved cell cycle arrest is induced to ensure cellular and genomic integrity during methionine starvation conditions. Methionine and its metabolites are critical for cell growth, proliferation, and development in all organisms. However, mechanisms of methionine perception are diverse. Here we review current knowledge about mechanisms of methionine sensing in yeast and mammalian cells, and will discuss the impact of methionine imbalance on cancer and aging. Full article
(This article belongs to the Special Issue Metabolites and Signaling Pathways)
►▼ Show Figures

Graphical abstract

11 pages, 1025 KiB  
Review
Metabolic Control of m6A RNA Modification
by Joohwan Kim and Gina Lee
Metabolites 2021, 11(2), 80; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11020080 - 30 Jan 2021
Cited by 24 | Viewed by 4063
Abstract
Nutrients and metabolic pathways regulate cell growth and cell fate decisions via epigenetic modification of DNA and histones. Another key genetic material, RNA, also contains diverse chemical modifications. Among these, N6-methyladenosine (m6A) is the most prevalent and evolutionarily conserved [...] Read more.
Nutrients and metabolic pathways regulate cell growth and cell fate decisions via epigenetic modification of DNA and histones. Another key genetic material, RNA, also contains diverse chemical modifications. Among these, N6-methyladenosine (m6A) is the most prevalent and evolutionarily conserved RNA modification. It functions in various aspects of developmental and disease states, by controlling RNA metabolism, such as stability and translation. Similar to other epigenetic processes, m6A modification is regulated by specific enzymes, including writers (methyltransferases), erasers (demethylases), and readers (m6A-binding proteins). As this is a reversible enzymatic process, metabolites can directly influence the flux of this reaction by serving as substrates and/or allosteric regulators. In this review, we will discuss recent understanding of the regulation of m6A RNA modification by metabolites, nutrients, and cellular metabolic pathways. Full article
(This article belongs to the Special Issue Metabolites and Signaling Pathways)
►▼ Show Figures

Figure 1

16 pages, 1365 KiB  
Review
Physiological Responses of Post-Dietary Effects: Lessons from Pre-Clinical and Clinical Studies
by Christy Yeung, Irisa Qianwen Shi and Hoon-Ki Sung
Metabolites 2021, 11(2), 62; https://0-doi-org.brum.beds.ac.uk/10.3390/metabo11020062 - 20 Jan 2021
Cited by 1 | Viewed by 2528
Abstract
Dieting regimens such as calorie restriction (CR) are among the most commonly practiced interventions for weight management and metabolic abnormalities. Due to its independence from pharmacological agents and considerable flexibility in regimens, many individuals turn to dieting as a form of mitigation and [...] Read more.
Dieting regimens such as calorie restriction (CR) are among the most commonly practiced interventions for weight management and metabolic abnormalities. Due to its independence from pharmacological agents and considerable flexibility in regimens, many individuals turn to dieting as a form of mitigation and maintenance of metabolic health. While metabolic benefits of CR have been widely studied, weight loss maintenance and metabolic benefits are reported to be lost overtime when the diet regimen has been terminated—referred to as post-dietary effects. Specifically, due to the challenges of long-term adherence and compliance to dieting, post-dietary repercussions such as body weight regain and loss of metabolic benefits pose as major factors in the efficacy of CR. Intermittent fasting (IF) regimens, which are defined by periodic energy restriction, have been deemed as more flexible, compliant, and easily adapted diet interventions that result in many metabolic benefits which resemble conventional CR diets. Many individuals find that IF regimens are easier to adhere to, resulting in fewer post-dietary effects; therefore, IF may be a more effective intervention. Unfortunately, there is a severe gap in current research regarding IF post-dietary effects. We recognize the importance of understanding the sustainability of dieting; as such, we will review the known physiological responses of CR post-dietary effects and its potential mechanisms through synthesizing lessons from both pre-clinical and clinical studies. This review aims to provide insight from a translational medicine perspective to allow for the development of more practical and effective diet interventions. We suggest more flexible and easily practiced dieting regimens such as IF due to its more adaptable and practical nature. Full article
(This article belongs to the Special Issue Metabolites and Signaling Pathways)
►▼ Show Figures

Figure 1

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-7
Back to TopTop