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The Role of Enzymes in Metabolic Processes
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The Role of Enzymes in Metabolic Processes

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

Deadline for manuscript submissions: 20 May 2025 | Viewed by 6562

Special Issue Editor

Prof. Dr. Koichi Fujisawa

E-Mail Website
Guest Editor
Department of Environmental Oncology, Institute of Industrial Ecological Sciences, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu 807-8555, Japan
Interests: energy metabolism; adenylate kinase; mitochonodria; oncology; hepatology; regenerative medicine; stem cell; mesenchymal stem cell
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cellular metabolism is an important function that regulates nutrient storage and energy production. Enzymes, in particular, play an important role in regulating metabolic processes, including glycolysis and the TCA cycle. Furthermore, metabolic processes are closely related to cell proliferation, cell death, and carcinogenesis, and the importance of analyzing their functions continues to grow. This Special Issue solicits papers on enzymes involved in metabolic processes.

Prof. Dr. Koichi Fujisawa
Guest Editor

Manuscript Submission Information

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Keywords

  • enzyme
  • metabolism
  • glycolysis
  • mitochondria
  • kinase
  • cell growth
  • carcinogenesis

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Published Papers (4 papers)

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Research

11 pages, 2379 KiB  
Article
Intradomain Allosteric Regulation of Soluble Epoxide Hydrolase by Its Substrates
by Shin Matsumura, Ayano Shida, Moeno Tsuchii, Mika Wada, Jimmy Charneau, Motonori Tsuji, Keiji Hasumi and Eriko Suzuki
Int. J. Mol. Sci. 2024, 25(24), 13496; https://doi.org/10.3390/ijms252413496 - 17 Dec 2024
Viewed by 988
Abstract
Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with epoxide hydrolase activity in the C-terminal domain (C-EH) and lipid phosphate phosphatase activity in the N-terminal domain (N-phos). The C-EH hydrolyzes bioactive epoxy fatty acids such as epoxyeicosatrienoic acid (EET). The N-phos hydrolyzes lipid [...] Read more.
Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with epoxide hydrolase activity in the C-terminal domain (C-EH) and lipid phosphate phosphatase activity in the N-terminal domain (N-phos). The C-EH hydrolyzes bioactive epoxy fatty acids such as epoxyeicosatrienoic acid (EET). The N-phos hydrolyzes lipid phosphomonesters, including the signaling molecules of lysophosphatidic acid (LPA). Here, we report that the C-EH and N-phos are reciprocally regulated by their respective substrates. Full-length sEH (sEH-FL) showed positive cooperativity toward the substrate for each domain. Similar cooperativity was found when truncated enzymes having only C- and N-terminal domains, sEH-C and sEH-N, respectively, were used, suggesting an intra-domain nature of the cooperativity. In addition, the N-phos substrate LPA inhibited C-EH activity in sEH-FL and sEH-C equally. Similarly, the C-EH substrate EET inhibited N-phos activity. Structural and kinetic data suggest the presence of allosteric sites in each domain of the sEH enzyme, which share the binding of LPA and EET. Thus, each of the two sEH activities is regulated by a substrate of its own and by that of the other domain. This mechanism may explain why sEH has evolved to have two different enzyme activities, which possibly allows sEH to balance the metabolism of bioactive lipids. Full article
(This article belongs to the Special Issue The Role of Enzymes in Metabolic Processes)
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21 pages, 3197 KiB  
Article
Plasmalogens Improve Lymphatic Clearance of Amyloid Beta from Mouse Brain and Cognitive Functions
by Alexander Shirokov, Daria Zlatogosrkaya, Viktoria Adushkina, Elena Vodovozova, Kristina Kardashevskaya, Ruslan Sultanov, Sergey Kasyanov, Inna Blokhina, Andrey Terskov, Maria Tzoy, Arina Evsyukova, Alexander Dubrovsky, Matvey Tuzhilkin, Inna Elezarova, Alexander Dmitrenko, Maria Manzhaeva, Valeria Krupnova, Anastasiia Semiachkina-Glushkovskaia, Egor Ilyukov, Dmitry Myagkov, Dmitry Tuktarov, Sergey Popov, Tymophey Inozemzev, Nikita Navolokin, Ivan Fedosov and Oxana Semyachkina-Glushkovskayaadd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2024, 25(23), 12552; https://doi.org/10.3390/ijms252312552 - 22 Nov 2024
Cited by 1 | Viewed by 1215
Abstract
Amyloid beta (Aβ) is a neuronal metabolic product that plays an important role in maintaining brain homeostasis. Normally, intensive brain Aβ formation is accompanied by its effective lymphatic removal. However, the excessive accumulation of brain Aβ is observed with age and during the [...] Read more.
Amyloid beta (Aβ) is a neuronal metabolic product that plays an important role in maintaining brain homeostasis. Normally, intensive brain Aβ formation is accompanied by its effective lymphatic removal. However, the excessive accumulation of brain Aβ is observed with age and during the development of Alzheimer’s disease (AD) leading to cognitive impairment and memory deficits. There is emerging evidence that plasmalogens (Pls), as one of the key brain lipids, may be beneficial for AD and cognitive aging. Here, we studied the effects of Pls on cognitive functions and the lymphatic clearance of Aβ from the brain of AD mice and mice of different ages. The results showed that Pls effectively reduce brain Aβ levels and facilitate learning in aged but not old mice. In AD mice, Pls improve the lymphatic clearance of Aβ that is accompanied by an increase in general motor activity and an improvement of the emotional status and learning ability. Thus, these findings suggest that Pls could be a promising candidate for the alternative or concomitant therapy of AD and age-related brain diseases to enhance the lymphatic clearance of Aβ from the brain and cognitive functions. Full article
(This article belongs to the Special Issue The Role of Enzymes in Metabolic Processes)
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17 pages, 315 KiB  
Article
Assessing the Usefulness of Interleukin-8 as a Biomarker of Inflammation and Metabolic Dysregulation in Dairy Cows
by Kamila Puppel, Jan Slósarz, Paweł Solarczyk, Grzegorz Grodkowski, Piotr Kostusiak, Aleksandra Kalińska, Marek Balcerak, Małgorzata Kunowska-Slósarz and Marcin Gołębiewski
Int. J. Mol. Sci. 2024, 25(20), 11129; https://doi.org/10.3390/ijms252011129 - 16 Oct 2024
Cited by 1 | Viewed by 1214
Abstract
The study aimed to evaluate interleukin-8 (IL-8) as a biomarker for udder inflammation in dairy cows and to explore its associations with various metabolic parameters indicative of systemic inflammation and metabolic dysregulation. Dairy cows (multiparous) were categorized into five somatic cell count (SCC) [...] Read more.
The study aimed to evaluate interleukin-8 (IL-8) as a biomarker for udder inflammation in dairy cows and to explore its associations with various metabolic parameters indicative of systemic inflammation and metabolic dysregulation. Dairy cows (multiparous) were categorized into five somatic cell count (SCC) classes: Class I (<100,000 cells/mL; n = 45), Class II (100,000–200,000 cells/mL; n = 62), Class III (201,000–400,000 cells/mL; n = 52), Class IV (401,000–1,000,000 cells/mL; n = 73), and Class V (>1,000,000 cells/mL; n = 56). The study quantified IL-8 levels and analyzed their correlations with NEFAs (non-esterified fatty acids), BHBA (beta-hydroxybutyrate), GGTP (gamma-glutamyltransferase), and AspAT (aspartate aminotransferase). IL-8 concentrations demonstrated a significant and progressive increase across the SCC classes, establishing a strong positive correlation with SCC (p < 0.01). Additionally, IL-8 levels exhibited positive correlations with GGTP (p < 0.01) and AspAT (p < 0.01), indicating that elevated IL-8 is associated with increased hepatic enzyme activities and potential liver dysfunction. Furthermore, IL-8 showed significant positive correlations with NEFAs (p < 0.01) and BHBA (p < 0.05), linking higher IL-8 levels to metabolic disturbances such as ketosis and negative energy balance. Variations in metabolic parameters, including NEFAs, BHBA, GGTP, and AspAT, across the SCC classes underscored the association between elevated SCC levels and metabolic dysregulation in dairy cows. These findings highlight the interrelated nature of the inflammatory responses and metabolic disturbances in dairy cattle, emphasizing that an elevated SCC not only signifies udder inflammation but also correlates with systemic metabolic alterations indicative of ketosis and liver damage. Full article
(This article belongs to the Special Issue The Role of Enzymes in Metabolic Processes)
16 pages, 4261 KiB  
Article
Inhibitory Efficacy of Main Components of Scutellaria baicalensis on the Interaction between Spike Protein of SARS-CoV-2 and Human Angiotensin-Converting Enzyme II
by Cheng-Han Lin, Ho-Ju Chang, Meng-Wei Lin, Xin-Rui Yang, Che-Hsiung Lee and Chih-Sheng Lin
Int. J. Mol. Sci. 2024, 25(5), 2935; https://doi.org/10.3390/ijms25052935 - 2 Mar 2024
Cited by 8 | Viewed by 2302
Abstract
Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of [...] Read more.
Blocking the interaction between the SARS-CoV-2 spike protein and the human angiotensin-converting enzyme II (hACE2) protein serves as a therapeutic strategy for treating COVID-19. Traditional Chinese medicine (TCM) treatments containing bioactive products could alleviate the symptoms of severe COVID-19. However, the emergence of SARS-CoV-2 variants has complicated the process of developing broad-spectrum drugs. As such, the aim of this study was to explore the efficacy of TCM treatments against SARS-CoV-2 variants through targeting the interaction of the viral spike protein with the hACE2 receptor. Antiviral activity was systematically evaluated using a pseudovirus system. Scutellaria baicalensis (S. baicalensis) was found to be effective against SARS-CoV-2 infection, as it mediated the interaction between the viral spike protein and the hACE2 protein. Moreover, the active molecules of S. baicalensis were identified and analyzed. Baicalein and baicalin, a flavone and a flavone glycoside found in S. baicalensis, respectively, exhibited strong inhibitory activities targeting the viral spike protein and the hACE2 protein, respectively. Under optimized conditions, virus infection was inhibited by 98% via baicalein-treated pseudovirus and baicalin-treated hACE2. In summary, we identified the potential SARS-CoV-2 inhibitors from S. baicalensis that mediate the interaction between the Omicron spike protein and the hACE2 receptor. Future studies on the therapeutic application of baicalein and baicalin against SARS-CoV-2 variants are needed. Full article
(This article belongs to the Special Issue The Role of Enzymes in Metabolic Processes)
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