Overexpression and inhibition of 3-hydroxy-3-methylglutaryl-CoA synthase affect central metabolic pathways in tobacco

2020 ◽  
Author(s):  
Pan Liao ◽  
Shiu-Cheung Lung ◽  
Wai Lung Chan ◽  
Menglong Hu ◽  
Geoffrey Kwai-Wai Kong ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Quantitative Proteomics ◽  
Tricarboxylic Acid Cycle ◽  
Specific Inhibitor ◽  
Primary Metabolism ◽  
Proteomics Analysis ◽  
Acetyl Coa ◽  
Cell Wall Modification ◽  
Mva Pathway ◽  
The Relationship

Abstract Little has been established on the relationship between the mevalonate (MVA) pathway and other metabolic pathways except for the sterol and glucosinolate biosynthesis pathways. In the MVA pathway, 3-hydroxy-3-methylglutaryl-CoA synthase (HMGS) catalyses the condensation of acetoacetyl-CoA and acetyl-CoA to form HMG-CoA. Our previous studies had shown that while the recombinant Brassica juncea HMGS1 (BjHMGS1) mutant S359A displayed 10-fold higher enzyme activity than wild-type (wt) BjHMGS1, transgenic tobacco overexpressing S359A (OE-S359A) exhibited higher sterol content, growth rate and seed yield than OE-wtBjHMGS1. Herein, untargeted proteomics and targeted metabolomics were employed to understand the phenotypic effects of HMGS overexpression in tobacco by examining which other metabolic pathways were affected. SWATH-MS quantitative proteomics analysis on OE-wtBjHMGS1 and OE-S359A identified the misregulation of proteins in primary metabolism and cell wall modification, while some proteins related to photosynthesis and the tricarboxylic acid cycle were upregulated in OE-S359A. Metabolomic analysis indicated corresponding changes in carbohydrate, amino acid and fatty acid contents in HMGS-OEs, and F-244, a specific inhibitor of HMGS, was applied successfully on tobacco to confirm these observations. Finally, the crystal structure of acetyl-CoA-liganded S359A revealed that improved activity of S359A likely resulted from a loss in hydrogen bonding between Ser359 and acyl-CoA which is evident in wtBjHMGS1. This work suggests that regulation of plant growth by HMGS can influence the central metabolic pathways. Furthermore, this study demonstrates that the application of the HMGS-specific inhibitor (F-244) in tobacco represents an effective approach for studying the HMGS/MVA pathway.

Metabolism-driven post-translational modifications of H3K9 in early bovine embryos

Reproduction ◽  
2021 ◽  
Vol 162 (3) ◽  
pp. 181-191
Author(s):  
Jessica Ispada ◽  
Aldcejam Martins da Fonseca Junior ◽  
Otávio Luiz Ramos Santos ◽  
Camila Bruna de Lima ◽  
Erika Cristina dos Santos ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Developmental Stages ◽  
De Novo ◽  
Blastocyst Stage ◽  
Developmental Model ◽  
Bovine Embryos ◽  
Acetyl Coa ◽  
Post Translational Modifications ◽  
The Relationship ◽  
Different Levels

Metabolic and molecular profiles were reported as different for bovine embryos with distinct kinetics during the first cleavages. In this study, we used this same developmental model (fast vs slow) to determine if the relationship between metabolism and developmental kinetics affects the levels of acetylation or tri-methylation at histone H3 lysine 9 (H3K9ac and H3K9me3, respectively). Fast and slow developing embryos presented different levels of H3K9ac and H3K9me3 from the earliest stages of development (40 and 96 hpi) and up to the blastocyst stage. For H3K9me3, both groups of embryos presented a wave of demethylation and de novo methylation, although it was more pronounced in fast than slow embryos, resulting in blastocysts with higher levels of this mark. The H3K9ac reprogramming profile was distinct between kinetics groups. While slow embryos presented a wave of deacetylation, followed by an increase in this mark at the blastocyst stage, fast embryos reduced this mark throughout all the developmental stages studied. H3K9me3 differences corresponded to writer and eraser transcript levels, while H3K9ac patterns were explained by metabolism-related gene expression. To verify if metabolic differences could alter levels of H3K9ac, embryos were cultured with sodium-iodoacetate (IA) or dichloroacetate (DCA) to disrupt the glycolytic pathway or increase acetyl-CoA production, respectively. IA reduced H3K9ac while DCA increased H3K9ac in blastocysts. Concluding, H3K9me3 and H3K9ac patterns differ between embryos with different kinetics, the second one explained by metabolic pathways involved in acetyl-CoA production. So far, this is the first study demonstrating a relationship between metabolic differences and histone post-translational modifications in bovine embryos.

Quantitative proteomics analysis reveals perturbation of lipid metabolic pathways in the liver of Atlantic cod (Gadus morhua) treated with PCB 153

2017 ◽  
Vol 185 ◽  
pp. 19-28 ◽  
Author(s):  
Fekadu Yadetie ◽  
Eystein Oveland ◽  
Anne Døskeland ◽  
Frode Berven ◽  
Anders Goksøyr ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Quantitative Proteomics ◽  
Gadus Morhua ◽  
Atlantic Cod ◽  
Proteomics Analysis

scholarly journals Indole-3-acetic acid regulates the central metabolic pathways in Escherichia coli

Microbiology ◽  
2006 ◽  
Vol 152 (8) ◽  
pp. 2421-2431 ◽  
Author(s):  
C. Bianco ◽  
E. Imperlini ◽  
R. Calogero ◽  
B. Senatore ◽  
P. Pucci ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
Mrna Levels ◽  
Glyoxylate Shunt ◽  
Acetyl Coa ◽  
Acid Cycle ◽  
E Coli ◽  
K 12

The physiological changes induced by indoleacetic acid (IAA) treatment were investigated in the totally sequenced Escherichia coli K-12 MG1655. DNA macroarrays were used to measure the mRNA levels for all the 4290 E. coli protein-coding genes; 50 genes (1.1 %) exhibited significantly different expression profiles. In particular, genes involved in the tricarboxylic acid cycle, the glyoxylate shunt and amino acid biosynthesis (leucine, isoleucine, valine and proline) were up-regulated, whereas the fermentative adhE gene was down-regulated. To confirm the indications obtained from the macroarray analysis the activity of 34 enzymes involved in central metabolism was measured; this showed an activation of the tricarboxylic acid cycle and the glyoxylate shunt. The malic enzyme, involved in the production of pyruvate, and pyruvate dehydrogenase, required for the channelling of pyruvate into acetyl-CoA, were also induced in IAA-treated cells. Moreover, it was shown that the enhanced production of acetyl-CoA and the decrease of NADH/NAD+ ratio are connected with the molecular process of the IAA response. The results demonstrate that IAA treatment is a stimulus capable of inducing changes in gene expression, enzyme activity and metabolite level involved in central metabolic pathways in E. coli.

Quantitative Proteomics Analysis Reveals Unique But Overlapping Protein Signatures in HIV Infection

2019 ◽  
Author(s):  
Maha Al-Mozaini ◽  
Ibtihag S. Alsharif ◽  
Al-Hussain J. Alzahrani ◽  
Zakia Shinwari ◽  
Magid Halim ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Quantitative Proteomics ◽  
Proteomics Analysis ◽  
Protein Signatures

scholarly journals The Role of Cell Metabolism in Innate Immune Memory

2020 ◽  
pp. 1-9
Author(s):  
Anaisa Valido Ferreira ◽  
Jorge Domiguéz-Andrés ◽  
Mihai Gheorghe Netea
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Cell Metabolism ◽  
Innate Immune ◽  
Immune Memory ◽  
Functional Changes ◽  
Trained Immunity ◽  
Health And Disease

Immunological memory is classically attributed to adaptive immune responses, but recent studies have shown that challenged innate immune cells can display long-term functional changes that increase nonspecific responsiveness to subsequent infections. This phenomenon, coined <i>trained immunity</i> or <i>innate immune memory</i>, is based on the epigenetic reprogramming and the rewiring of intracellular metabolic pathways. Here, we review the different metabolic pathways that are modulated in trained immunity. Glycolysis, oxidative phosphorylation, the tricarboxylic acid cycle, amino acid, and lipid metabolism are interplaying pathways that are crucial for the establishment of innate immune memory. Unraveling this metabolic wiring allows for a better understanding of innate immune contribution to health and disease. These insights may open avenues for the development of future therapies that aim to harness or dampen the power of the innate immune response.

scholarly journals Mitochondrial Sirtuins in Reproduction

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1047
Author(s):  
Giovanna Di Emidio ◽  
Stefano Falone ◽  
Paolo Giovanni Artini ◽  
Fernanda Amicarelli ◽  
Anna Maria D’Alessandro ◽  
...  
Keyword(s):  
Stress Responses ◽  
Metabolic Pathways ◽  
Redox Balance ◽  
Antioxidant Defenses ◽  
Metabolic Abnormalities ◽  
Female Reproduction ◽  
Mitochondrial Dysfunctions ◽  
Early Embryos ◽  
The Relationship

Mitochondria act as hubs of numerous metabolic pathways. Mitochondrial dysfunctions contribute to altering the redox balance and predispose to aging and metabolic alterations. The sirtuin family is composed of seven members and three of them, SIRT3-5, are housed in mitochondria. They catalyze NAD+-dependent deacylation and the ADP-ribosylation of mitochondrial proteins, thereby modulating gene expression and activities of enzymes involved in oxidative metabolism and stress responses. In this context, mitochondrial sirtuins (mtSIRTs) act in synergistic or antagonistic manners to protect from aging and aging-related metabolic abnormalities. In this review, we focus on the role of mtSIRTs in the biological competence of reproductive cells, organs, and embryos. Most studies are focused on SIRT3 in female reproduction, providing evidence that SIRT3 improves the competence of oocytes in humans and animal models. Moreover, SIRT3 protects oocytes, early embryos, and ovaries against stress conditions. The relationship between derangement of SIRT3 signaling and the imbalance of ROS and antioxidant defenses in testes has also been demonstrated. Very little is known about SIRT4 and SIRT5 functions in the reproductive system. The final goal of this work is to understand whether sirtuin-based signaling may be taken into account as potential targets for therapeutic applications in female and male infertility.

scholarly journals Quantitative Proteomics Analysis Reveals Unique but Overlapping Protein Signatures in HIV Infections

2021 ◽  
Author(s):  
Maha Al-Mozaini ◽  
Ibtihag Alsharif ◽  
Alhusain Alzahrani ◽  
Zakia Shinwari ◽  
Magid Halim ◽  
...  
Keyword(s):  
Quantitative Proteomics ◽  
Hiv Infections ◽  
Proteomics Analysis ◽  
Protein Signatures

scholarly journals To Stretch the Boundary of Secondary Metabolite Production in Plant Cell-Based Bioprocessing: Anthocyanin as a Case Study

2004 ◽  
Vol 2004 (5) ◽  
pp. 264-271 ◽  
Author(s):  
Wei Zhang ◽  
Chris Franco ◽  
Chris Curtin ◽  
Simon Conn
Keyword(s):  
Secondary Metabolites ◽  
Plant Cell ◽  
Metabolic Pathways ◽  
Anthocyanin Biosynthesis ◽  
Rational Approach ◽  
Great Promise ◽  
Primary Metabolism ◽  
Global Correlation ◽  
Empirical Level

Plant cells and tissue cultures hold great promise for controlled production of a myriad of useful secondary metabolites on demand. The current yield and productivity cannot fulfill the commercial goal of a plant cell-based bioprocess for the production of most secondary metabolites. In order to stretch the boundary, recent advances, new directions and opportunities in plant cell-based bioprocessing, have been critically examined for the 10 years from 1992 to 2002. A review of the literature indicated that most of the R&D work was devoted predominantly to studies at an empirical level. A rational approach to molecular plant cell bioprocessing based on the fundamental understanding of metabolic pathways and their regulations is urgently required to stimulate further advances; however, the strategies and technical framework are still being developed. It is the aim of this review to take a step forward in framing workable strategies and technologies for molecular plant cell-based bioprocessing. Using anthocyanin biosynthesis as a case study, an integrated postgenomic approach has been proposed. This combines the functional analysis of metabolic pathways for biosynthesis of a particular metabolite from profiling of gene expression and protein expression to metabolic profiling. A global correlation not only can thus be established at the three molecular levels, but also places emphasis on the interactions between primary metabolism and secondary metabolism; between competing and/or complimentary pathways; and between biosynthetic and post-biosynthetic events.

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