scholarly journals Lipoic Acid Metabolism in Microbial Pathogens

2010 ◽  
Vol 74 (2) ◽  
pp. 200-228 ◽  
Author(s):  
Maroya D. Spalding ◽  
Sean T. Prigge
Keyword(s):  
Lipoic Acid ◽  
Acid Metabolism ◽  
De Novo ◽  
Living Cells ◽  
Microbial Pathogens ◽  
Pentanoic Acid ◽  
Free Living ◽  
Oxidative Defense ◽  
Intermediate Metabolism

SUMMARY Lipoic acid [(R)-5-(1,2-dithiolan-3-yl)pentanoic acid] is an enzyme cofactor required for intermediate metabolism in free-living cells. Lipoic acid was discovered nearly 60 years ago and was shown to be covalently attached to proteins in several multicomponent dehydrogenases. Cells can acquire lipoate (the deprotonated charge form of lipoic acid that dominates at physiological pH) through either scavenging or de novo synthesis. Microbial pathogens implement these basic lipoylation strategies with a surprising variety of adaptations which can affect pathogenesis and virulence. Similarly, lipoylated proteins are responsible for effects beyond their classical roles in catalysis. These include roles in oxidative defense, bacterial sporulation, and gene expression. This review surveys the role of lipoate metabolism in bacterial, fungal, and protozoan pathogens and how these organisms have employed this metabolism to adapt to niche environments.

scholarly journals Fluorinated Mannosides Inhibit Cellular Fucosylation.

2020 ◽  
Author(s):  
Johan Pijnenborg ◽  
Emiel Rossing ◽  
Marek Noga ◽  
Willem Titulaer ◽  
Raisa Veizaj ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
De Novo ◽  
Genetic Disorders ◽  
Living Cells ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Inflammation ◽  
Mannose Derivatives ◽  
Potential Therapeutics

Fucose sugars are expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a novel class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis. We demonstrate that cell permeable fluorinated mannoside 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

scholarly journals Reprogramming of fatty acid metabolism in cancer

2019 ◽  
Vol 122 (1) ◽  
pp. 4-22 ◽  
Author(s):  
Nikos Koundouros ◽  
George Poulogiannis
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cancer Cells ◽  
Cancer Progression ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
De Novo ◽  
Great Promise ◽  
Molecular Heterogeneity

AbstractA common feature of cancer cells is their ability to rewire their metabolism to sustain the production of ATP and macromolecules needed for cell growth, division and survival. In particular, the importance of altered fatty acid metabolism in cancer has received renewed interest as, aside their principal role as structural components of the membrane matrix, they are important secondary messengers, and can also serve as fuel sources for energy production. In this review, we will examine the mechanisms through which cancer cells rewire their fatty acid metabolism with a focus on four main areas of research. (1) The role of de novo synthesis and exogenous uptake in the cellular pool of fatty acids. (2) The mechanisms through which molecular heterogeneity and oncogenic signal transduction pathways, such as PI3K–AKT–mTOR signalling, regulate fatty acid metabolism. (3) The role of fatty acids as essential mediators of cancer progression and metastasis, through remodelling of the tumour microenvironment. (4) Therapeutic strategies and considerations for successfully targeting fatty acid metabolism in cancer. Further research focusing on the complex interplay between oncogenic signalling and dysregulated fatty acid metabolism holds great promise to uncover novel metabolic vulnerabilities and improve the efficacy of targeted therapies.

scholarly journals Fluorinated rhamnosides inhibit cellular fucosylation

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Johan F. A. Pijnenborg ◽  
Emiel Rossing ◽  
Jona Merx ◽  
Marek J. Noga ◽  
Willem H. C. Titulaer ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
De Novo ◽  
Genetic Disorders ◽  
Living Cells ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Inflammation ◽  
Mannose Derivatives ◽  
Potential Therapeutics

AbstractThe sugar fucose is expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis via competitive GMDS inhibition. We demonstrate that cell permeable fluorinated rhamnose 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

scholarly journals Fluorinated Mannosides Inhibit Cellular Fucosylation.

2020 ◽  
Author(s):  
Johan Pijnenborg ◽  
Emiel Rossing ◽  
Marek Noga ◽  
Willem Titulaer ◽  
Raisa Veizaj ◽  
...  
Keyword(s):  
Mammalian Cell ◽  
De Novo ◽  
Genetic Disorders ◽  
Living Cells ◽  
Aberrant Expression ◽  
Physiological Processes ◽  
Cancer Inflammation ◽  
Mannose Derivatives ◽  
Potential Therapeutics

Fucose sugars are expressed on mammalian cell membranes as part of glycoconjugates and mediates essential physiological processes. The aberrant expression of fucosylated glycans has been linked to pathologies such as cancer, inflammation, infection, and genetic disorders. Tools to modulate fucose expression on living cells are needed to elucidate the biological role of fucose sugars and the development of potential therapeutics. Herein, we report a novel class of fucosylation inhibitors directly targeting de novo GDP-fucose biosynthesis. We demonstrate that cell permeable fluorinated mannoside 1-phosphate derivatives (Fucotrim I & II) are metabolic prodrugs that are metabolized to their respective GDP-mannose derivatives and efficiently inhibit cellular fucosylation.

scholarly journals Lipoic Acid Metabolism as a Potential Chemotherapeutic Target Against Plasmodium falciparum and Staphylococcus aureus

2021 ◽  
Vol 9 ◽  
Author(s):  
Sun Liu Rei Yan ◽  
Felipe Wakasuqui ◽  
Xiaochen Du ◽  
Matthew R. Groves ◽  
Carsten Wrenger
Keyword(s):  
Staphylococcus Aureus ◽  
Plasmodium Falciparum ◽  
Organic Compound ◽  
Lipoic Acid ◽  
Pyruvate Dehydrogenase ◽  
Posttranslational Modification ◽  
Acid Metabolism ◽  
Recent Literature ◽  
And Staphylococcus Aureus

Lipoic acid (LA) is an organic compound that plays a key role in cellular metabolism. It participates in a posttranslational modification (PTM) named lipoylation, an event that is highly conserved and that occurs in multimeric metabolic enzymes of very distinct microorganisms such as Plasmodium sp. and Staphylococcus aureus, including pyruvate dehydrogenase (PDH) and α-ketoglutarate dehydrogenase (KDH). In this mini review, we revisit the recent literature regarding LA metabolism in Plasmodium sp. and Staphylococcus aureus, by covering the lipoate ligase proteins in both microorganisms, the role of lipoate ligase proteins and insights for possible inhibitors of lipoate ligases.

scholarly journals Obesity and Cancer Progression: Is There a Role of Fatty Acid Metabolism?

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Seher Balaban ◽  
Lisa S. Lee ◽  
Mark Schreuder ◽  
Andrew J. Hoy
Keyword(s):  
Fatty Acid ◽  
Cancer Progression ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
De Novo ◽  
Metabolic Characteristics ◽  
Potential Link ◽  
Mitochondrial Oxidation ◽  
Obesity And Cancer

Currently, there is renewed interest in elucidating the metabolic characteristics of cancer and how these characteristics may be exploited as therapeutic targets. Much attention has centered on glucose, glutamine andde novolipogenesis, yet the metabolism of fatty acids that arise from extracellular, as well as intracellular, stores as triacylglycerol has received much less attention. This review focuses on the key pathways of fatty acid metabolism, including uptake, esterification, lipolysis, and mitochondrial oxidation, and how the regulators of these pathways are altered in cancer. Additionally, we discuss the potential link that fatty acid metabolism may serve between obesity and changes in cancer progression.

Posttransplant CMV infection and the role of immunosuppression (Sponsor: Novartis Pharma GmbH, Nürnberg)

2016 ◽  
Vol 04 (01) ◽  
pp. 4-10
Keyword(s):  
Lower Incidence ◽  
Paradigm Shift ◽  
Mtor Inhibitor ◽  
De Novo ◽  
Expert Panel ◽  
Risk Of Infection ◽  
Cmv Infection ◽  
Expert Meeting ◽  
Selection Of

AbstractImmunosuppression permits graft survival after transplantation and consequently a longer and better life. On the other hand, it increases the risk of infection, for instance with cytomegalovirus (CMV). However, the various available immunosuppressive therapies differ in this regard. One of the first clinical trials using de novo everolimus after kidney transplantation [1] already revealed a considerably lower incidence of CMV infection in the everolimus arms than in the mycophenolate mofetil (MMF) arm. This result was repeatedly confirmed in later studies [2–4]. Everolimus is now considered a substance with antiviral properties. This article is based on the expert meeting “Posttransplant CMV infection and the role of immunosuppression”. The expert panel called for a paradigm shift: In a CMV prevention strategy the targeted selection of the immunosuppressive therapy is also a key element. For patients with elevated risk of CMV, mTOR inhibitor-based immunosuppression is advantageous as it is associated with a significantly lower incidence of CMV events.

The Signaling Pathways in Nitric Oxide Production by Neutrophils Exposed to N-nitrosodimethylamine

2018 ◽  
Vol 16 (2) ◽  
pp. 194-199
Author(s):  
Wioletta Ratajczak-Wrona ◽  
Ewa Jablonska
Keyword(s):  
Nitric Oxide ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Polymorphonuclear Neutrophils ◽  
Microbial Pathogens ◽  
Human Neutrophils ◽  
No Production ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Background: Polymorphonuclear neutrophils (PMNs) play a crucial role in the innate immune system’s response to microbial pathogens through the release of reactive nitrogen species, including Nitric Oxide (NO). </P><P> Methods: In neutrophils, NO is produced by the inducible Nitric Oxide Synthase (iNOS), which is regulated by various signaling pathways and transcription factors. N-nitrosodimethylamine (NDMA), a potential human carcinogen, affects immune cells. NDMA plays a major part in the growing incidence of cancers. Thanks to the increasing knowledge on the toxicological role of NDMA, the environmental factors that condition the exposure to this compound, especially its precursors- nitrates arouse wide concern. Results: In this article, we present a detailed summary of the molecular mechanisms of NDMA’s effect on the iNOS-dependent NO production in human neutrophils. Conclusion: This research contributes to a more complete understanding of the mechanisms that explain the changes that occur during nonspecific cellular responses to NDMA toxicity.

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