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New Insights on Cell Metabolism
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New Insights on Cell Metabolism

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

Deadline for manuscript submissions: closed (31 August 2021) | Viewed by 21522

Special Issue Editor

Prof. Dr. Enrique Meléndez-Hevia

E-Mail Website
Guest Editor
Instituto del Metabolismo Celular, Calle Manuel de Fallanº15, 38208 Tenerife, Canary Islands, La Laguna, Spain
Interests: cell metabolism; evolution and natural selection; phylogeny; evolution of metabolism; metabolic control theory (control analysis); degenerative and metabolic diseases (osteoarthritis; diabetes, hypertension, obesity (metabolic syndrome); cancer)
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

In recent years, the study of metabolism seems to have decreased in interest to some classic researchers—and also in some classical journals—in the field, and to those who have to apply it. This is perhaps because it is thought that the “metabolic chart” is considered finished. The practice of medicine is still very classic in many cases, without attending to new discoveries on metabolism. Perhaps this is because it is thought that the current challenges of medicine are not focussed on the way a mechanism that is considered very stable can indicate something new, and whose transcendence in health is minimal. However, current studies of cellular metabolism are revealing a panorama that is enriching our classic knowledge of this chemical machinery of cells. The contributions of different approaches from biochemists, biophysicists, and physiologists through experimental, theoretical, computerized knowledge and information about the genome, which has a broad range of new applications, some of which are unexpected, to many research fields, and for modern medicine in particular. The objective of this Special Issue is an update of this panorama, which can serve readers to learn new approaches and results, and new ways to apply them, and to authors to present their innovative results. The aim of this Special Issue is to provide this information in an interdisciplinary way. This means that authors will endeavor to present their results so that researchers from other fields can understand them well, avoiding unnecessary technical terms.

Prof. Dr. Enrique Meléndez-Hevia
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. 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

  • experimental approaches
  • genomics and proteomics with special attention to enzymes
  • metabolomics
  • computer studies
  • metabolic design
  • theoretical approaches
  • evolution of metabolism
  • energy metabolism
  • metabolic nutrition (new concepts about essential or indispensable amino acids, fatty acids, and vitamins)
  • new applications of metabolism to health, medicine, and sport, including degenerative and infectious diseases, and cancer

Published Papers (5 papers)

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Research

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15 pages, 3038 KiB  
Article
Bioenergetic Alterations of Metabolic Redox Coenzymes as NADH, FAD and FMN by Means of Fluorescence Lifetime Imaging Techniques
by Sviatlana Kalinina, Christian Freymueller, Nilanjon Naskar, Bjoern von Einem, Kirsten Reess, Ronald Sroka and Angelika Rueck
Int. J. Mol. Sci. 2021, 22(11), 5952; https://doi.org/10.3390/ijms22115952 - 31 May 2021
Cited by 25 | Viewed by 3200
Abstract
Metabolic FLIM (fluorescence lifetime imaging) is used to image bioenergetic status in cells and tissue. Whereas an attribution of the fluorescence lifetime of coenzymes as an indicator for cell metabolism is mainly accepted, it is debated whether this is valid for the redox [...] Read more.
Metabolic FLIM (fluorescence lifetime imaging) is used to image bioenergetic status in cells and tissue. Whereas an attribution of the fluorescence lifetime of coenzymes as an indicator for cell metabolism is mainly accepted, it is debated whether this is valid for the redox state of cells. In this regard, an innovative algorithm using the lifetime characteristics of nicotinamide adenine dinucleotide (phosphate) (NAD(P)H) and flavin adenine dinucleotide (FAD) to calculate the fluorescence lifetime induced redox ratio (FLIRR) has been reported so far. We extended the FLIRR approach and present new results, which includes FLIM data of the various enzymes, such as NAD(P)H, FAD, as well as flavin mononucleotide (FMN). Our algorithm uses a two-exponential fitting procedure for the NAD(P)H autofluorescence and a three-exponential fit of the flavin signal. By extending the FLIRR approach, we introduced FLIRR1 as protein-bound NAD(P)H related to protein-bound FAD, FLIRR2 as protein-bound NAD(P)H related to free (unbound) FAD and FLIRR3 as protein-bound NAD(P)H related to protein-bound FMN. We compared the significance of extended FLIRR to the metabolic index, defined as the ratio of protein-bound NAD(P)H to free NAD(P)H. The statistically significant difference for tumor and normal cells was found to be highest for FLIRR1. Full article
(This article belongs to the Special Issue New Insights on Cell Metabolism)
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17 pages, 5862 KiB  
Article
Functional Characterisation of Three Glycine N-Acyltransferase Variants and the Effect on Glycine Conjugation to Benzoyl–CoA
by Johann M. Rohwer, Chantelle Schutte and Rencia van der Sluis
Int. J. Mol. Sci. 2021, 22(6), 3129; https://doi.org/10.3390/ijms22063129 - 18 Mar 2021
Cited by 3 | Viewed by 5290
Abstract
The glycine conjugation pathway in humans is involved in the metabolism of natural substrates and the detoxification of xenobiotics. The interactions between the various substrates in this pathway and their competition for the pathway enzymes are currently unknown. The pathway consists of a [...] Read more.
The glycine conjugation pathway in humans is involved in the metabolism of natural substrates and the detoxification of xenobiotics. The interactions between the various substrates in this pathway and their competition for the pathway enzymes are currently unknown. The pathway consists of a mitochondrial xenobiotic/medium-chain fatty acid: coenzyme A (CoA) ligase (ACSM2B) and glycine N-acyltransferase (GLYAT). The catalytic mechanism and substrate specificity of both of these enzymes have not been thoroughly characterised. In this study, the level of evolutionary conservation of GLYAT missense variants and haplotypes were analysed. From these data, haplotype variants were selected (156Asn > Ser, [17Ser > Thr,156Asn > Ser] and [156Asn > Ser,199Arg > Cys]) in order to characterise the kinetic mechanism of the enzyme over a wide range of substrate concentrations. The 156Asn > Ser haplotype has the highest frequency and the highest relative enzyme activity in all populations studied, and hence was used as the reference in this study. Cooperative substrate binding was observed, and the kinetic data were fitted to a two-substrate Hill equation. The coding region of the GLYAT gene was found to be highly conserved and the rare 156Asn > Ser,199Arg > Cys variant negatively affected the relative enzyme activity. Even though the 156Asn > Ser,199Arg > Cys variant had a higher affinity for benzoyl-CoA (s0.5,benz = 61.2 µM), kcat was reduced to 9.8% of the most abundant haplotype 156Asn > Ser (s0.5,benz = 96.6 µM), while the activity of 17Ser > Thr,156Asn > Ser (s0.5,benz = 118 µM) was 73% of 156Asn > Ser. The in vitro kinetic analyses of the effect of the 156Asn > Ser,199Arg > Cys variant on human GLYAT enzyme activity indicated that individuals with this haplotype might have a decreased ability to metabolise benzoate when compared to individuals with the 156Asn > Ser variant. Furthermore, the accumulation of acyl-CoA intermediates can inhibit ACSM2B leading to a reduction in mitochondrial energy production. Full article
(This article belongs to the Special Issue New Insights on Cell Metabolism)
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16 pages, 3062 KiB  
Article
Aerobic Exercise Ameliorates Cancer Cachexia-Induced Muscle Wasting through Adiponectin Signaling
by Makoto Morinaga, Naoki Sako, Mari Isobe, Sachiko Lee-Hotta, Hideshi Sugiura and Satoshi Kametaka
Int. J. Mol. Sci. 2021, 22(6), 3110; https://doi.org/10.3390/ijms22063110 - 18 Mar 2021
Cited by 17 | Viewed by 3138
Abstract
Cachexia is a multifactorial syndrome characterized by muscle loss that cannot be reversed by conventional nutritional support. To uncover the molecular basis underlying the onset of cancer cachectic muscle wasting and establish an effective intervention against muscle loss, we used a cancer cachectic [...] Read more.
Cachexia is a multifactorial syndrome characterized by muscle loss that cannot be reversed by conventional nutritional support. To uncover the molecular basis underlying the onset of cancer cachectic muscle wasting and establish an effective intervention against muscle loss, we used a cancer cachectic mouse model and examined the effects of aerobic exercise. Aerobic exercise successfully suppressed muscle atrophy and activated adiponectin signaling. Next, a cellular model for cancer cachectic muscle atrophy using C2C12 myotubes was prepared by treating myotubes with a conditioned medium from a culture of colon-26 cancer cells. Treatment of the atrophic myotubes with recombinant adiponectin was protective against the thinning of cells through the increased production of p-mTOR and suppression of LC3-II. Altogether, these findings suggest that the activation of adiponectin signaling could be part of the molecular mechanisms by which aerobic exercise ameliorates cancer cachexia-induced muscle wasting. Full article
(This article belongs to the Special Issue New Insights on Cell Metabolism)
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Review

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19 pages, 8431 KiB  
Review
Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions
by Antonia Donat, Paul-Richard Knapstein, Shan Jiang, Anke Baranowsky, Tobias-Malte Ballhause, Karl-Heinz Frosch and Johannes Keller
Int. J. Mol. Sci. 2021, 22(8), 4120; https://doi.org/10.3390/ijms22084120 - 16 Apr 2021
Cited by 18 | Viewed by 5083
Abstract
Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. [...] Read more.
Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy. In turn, clinical conditions associated with impaired glucose metabolism, including type I and type II diabetes and anorexia nervosa, are associated with impaired bone turnover. As osteoblasts are required for collagen synthesis and matrix mineralization, they represent one of the most important targets for pharmacological augmentation of bone mass. To fulfill their function, osteoblasts primarily utilize glucose through aerobic glycolysis, a process which is regulated by various molecular switches and generates adenosine triphosphate rapidly. In this regard, researchers have been investigating the complex processes of energy utilization in osteoblasts in recent years, not only to improve bone turnover in metabolic disease, but also to identify novel treatment options for primary bone diseases. This review focuses on the metabolism of glucose in osteoblasts in physiological and pathophysiological conditions. Full article
(This article belongs to the Special Issue New Insights on Cell Metabolism)
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23 pages, 2181 KiB  
Review
Functional Fine-Tuning of Metabolic Pathways by the Endocannabinoid System—Implications for Health and Disease
by Estefanía Moreno, Milena Cavic and Enric I. Canela
Int. J. Mol. Sci. 2021, 22(7), 3661; https://doi.org/10.3390/ijms22073661 - 1 Apr 2021
Cited by 13 | Viewed by 4009
Abstract
The endocannabinoid system (ECS) employs a huge network of molecules (receptors, ligands, and enzymatic machinery molecules) whose interactions with other cellular networks have still not been fully elucidated. Endogenous cannabinoids are molecules with the primary function of control of multiple metabolic pathways. Maintenance [...] Read more.
The endocannabinoid system (ECS) employs a huge network of molecules (receptors, ligands, and enzymatic machinery molecules) whose interactions with other cellular networks have still not been fully elucidated. Endogenous cannabinoids are molecules with the primary function of control of multiple metabolic pathways. Maintenance of tissue and cellular homeostasis by functional fine-tuning of essential metabolic pathways is one of the key characteristics of the ECS. It is implicated in a variety of physiological and pathological states and an attractive pharmacological target yet to reach its full potential. This review will focus on the involvement of ECS in glucose and lipid metabolism, food intake regulation, immune homeostasis, respiratory health, inflammation, cancer and other physiological and pathological states will be substantiated using freely available data from open-access databases, experimental data and literature review. Future directions should envision capturing its diversity and exploiting pharmacological options beyond the classical ECS suspects (exogenous cannabinoids and cannabinoid receptor monomers) as signaling through cannabinoid receptor heteromers offers new possibilities for different biochemical outcomes in the cell. Full article
(This article belongs to the Special Issue New Insights on Cell Metabolism)
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