scholarly journals Evolution of enzyme levels in metabolic pathways: A theoretical approach. Part 2

2021 ◽  
Author(s):  
Charlotte Coton ◽  
Christine Dillmann ◽  
Dominique de Vienne
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Networks ◽  
Cell Function ◽  
Enzyme Concentration ◽  
Adaptive Landscape ◽  
Selective Neutrality ◽  
Simplifying Assumptions ◽  
Selection For ◽  
The Relationship ◽  
Competition For Resources

Metabolism is essential for cell function and adaptation. Because of their central role in metabolism, kinetic parameters and enzyme concentrations are under constant selective pressure to adapt the fluxes of the metabolic networks to the needs of the organism. In the line of various studies dealing with enzyme evolution, we recently developed a model of evolution of enzyme concentrations under selection for increased flux, considered as a proxy of fitness (Coton 2021). Taking into account two realistic cellular constraints, competition for resources and co-regulations, we determined the evolutionary equilibria and the ranges of neutral variations of enzyme concentrations. In this article, we give more generality to this model, by considering that the enzymes of a pathway can belong to different groups of co-regulation. We determined the equilibria and showed that the constraints modify the adaptive landscape by limiting the number of independent dimensions. We also showed that any trade-off between enzyme concentration is sufficient to limit the flux and to relax selection for increasing other enzyme concentrations. Even though the model is based on simplifying assumptions, the complexity of the relationship between enzyme concentrations prevents the analysis of selective neutrality.

scholarly journals How does resource supply affect evolutionary diversification?

2006 ◽  
Vol 274 (1606) ◽  
pp. 73-78 ◽  
Author(s):  
Alex R Hall ◽  
Nick Colegrave
Keyword(s):  
Latitudinal Gradients ◽  
Alternative Mechanism ◽  
Evolutionary Diversification ◽  
Wide Range ◽  
Spatially Homogeneous ◽  
Selection For ◽  
The Relationship ◽  
Competition For Resources ◽  
Unimodal Relationship ◽  
Niche Diversification

The availability of different resources in the environment can affect the outcomes of evolutionary diversification. A unimodal distribution of diversity with resource supply has been widely observed and explained previously in the context of selection acting in a spatially heterogeneous environment. Here, we propose an alternative mechanism to explain the relationship between resource supply and diversification that is based on selection for exploitation of different resources. To test this mechanism, we conducted a selection experiment using the bacterium Pseudomonas fluorescens in spatially homogeneous environments over a wide range of resource supply rates. Our results show that niche diversification peaks at intermediate levels of resource availability. We suggest that this unimodal relationship is due to evolutionary diversification that is driven by competition for resources but constrained by the ecological opportunity represented by different resource types. These processes may underlie some general patterns of diversity, including latitudinal gradients in species richness and the effects of anthropogenic enrichment of the environment.

The Relationship of Fasting Free Fatty Acids, Adipose Tissue, Insulin Resistance, and Fasting Glucose Concentrations with Subsequent ß-Cell Function in Nondiabetic Subjects

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1812-P
Author(s):  
MARIA D. HURTADO ◽  
J.D. ADAMS ◽  
MARCELLO C. LAURENTI ◽  
CHIARA DALLA MAN ◽  
CLAUDIO COBELLI ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Free Fatty Acids ◽  
Cell Function ◽  
Fasting Glucose ◽  
Relationship Of ◽  
The Relationship

MiR-493 Induces Cytotoxic Autophagy in Prostate Cancer Cells through Regulation on PHLPP2

2020 ◽  
Vol 21 (14) ◽  
pp. 1451-1456 ◽  
Author(s):  
Jun Deng ◽  
Ming Ma ◽  
Wei Jiang ◽  
Liangliang Zheng ◽  
Suping Cui
Keyword(s):  
Prostate Cancer ◽  
Protein Expression ◽  
Cell Function ◽  
Mrna Levels ◽  
Prostate Cancer Cells ◽  
Potent Inducer ◽  
Qrt Pcr ◽  
Autophagy Gene ◽  
The Relationship ◽  
Cancer Inhibition

Background: MiR-493 promotes the proliferation of prostate cancer (PC) cells by targeting PHLPP2. We aimed to explore the relationship between miR-493 and autophagy in PC. Methods: qRT-PCR and western blotting were used to determine the mRNA levels and protein expression of miR-493, PHLPP2, autophagy gene BECN1 and ATG7 in PC cells. The autophagy gene expression was determined after PC cells transfected with miR-493 precursor or PHLPP2 precursor. Corresponding changes of autophagy phenotype and PC cell function were also studied. Results: The mRNA levels and protein expression of miR-493, PHLPP2, BECN1 and ATG7 in PC cells were significantly decreased in PC cells. Overexpression of miR-493 or PHLPP2 markedly upregulated the expression levels of BECN1 and ATG7 in PC cells. Overexpression of miR-493 and PHLPP2 markedly promoted autophagy, and inhibited the invasion and cloning formation of PC cells. Conclusion: MiR-493 is a potent inducer of cytotoxic autophagy that leads to prostate cancer inhibition by regulating on PHLPP2.

scholarly journals Dynamic histone acetylation in floral volatile synthesis and emission in petunia flowers

2021 ◽  
Author(s):  
Ryan M Patrick ◽  
Xing-Qi Huang ◽  
Natalia Dudareva ◽  
Ying Li
Keyword(s):  
Transcriptional Activation ◽  
Metabolic Pathways ◽  
Transcriptional Repression ◽  
Metabolic Networks ◽  
Underlying Mechanism ◽  
Expression Of Genes ◽  
Genome Wide ◽  
Chemical Inhibitors ◽  
Volatile Organic ◽  
Floral Volatile

Abstract Biosynthesis of secondary metabolites relies on primary metabolic pathways to provide precursors, energy, and cofactors, thus requiring coordinated regulation of primary and secondary metabolic networks. However, to date, it remains largely unknown how this coordination is achieved. Using Petunia hybrida flowers, which emit high levels of phenylpropanoid/benzenoid volatile organic compounds (VOCs), we uncovered genome-wide dynamic deposition of histone H3 lysine 9 acetylation (H3K9ac) during anthesis as an underlying mechanism to coordinate primary and secondary metabolic networks. The observed epigenome reprogramming is accompanied by transcriptional activation at gene loci involved in primary metabolic pathways that provide precursor phenylalanine, as well as secondary metabolic pathways to produce volatile compounds. We also observed transcriptional repression among genes involved in alternative phenylpropanoid branches that compete for metabolic precursors. We show that GNAT family histone acetyltransferase(s) (HATs) are required for the expression of genes involved in VOC biosynthesis and emission, by using chemical inhibitors of HATs, and by knocking down a specific HAT gene, ELP3, through transient RNAi. Together, our study supports that regulatory mechanisms at chromatin level may play an essential role in activating primary and secondary metabolic pathways to regulate VOC synthesis in petunia flowers.

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 Comprehensive Plasma Metabolomic Profile of Patients with Advanced Neuroendocrine Tumors (NETs). Diagnostic and Biological Relevance

Cancers ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 2634
Author(s):  
Beatriz Soldevilla ◽  
Angeles López-López ◽  
Alberto Lens-Pardo ◽  
Carlos Carretero-Puche ◽  
Angeles Lopez-Gonzalvez ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Networks ◽  
Tca Cycle ◽  
Metabolomic Profile ◽  
Diagnostic Potential ◽  
The Tca Cycle ◽  
Novel Biomarkers ◽  
Potential Methods ◽  
Clinical Potential ◽  
First Time

Purpose: High-throughput “-omic” technologies have enabled the detailed analysis of metabolic networks in several cancers, but NETs have not been explored to date. We aim to assess the metabolomic profile of NET patients to understand metabolic deregulation in these tumors and identify novel biomarkers with clinical potential. Methods: Plasma samples from 77 NETs and 68 controls were profiled by GC−MS, CE−MS and LC−MS untargeted metabolomics. OPLS-DA was performed to evaluate metabolomic differences. Related pathways were explored using Metaboanalyst 4.0. Finally, ROC and OPLS-DA analyses were performed to select metabolites with biomarker potential. Results: We identified 155 differential compounds between NETs and controls. We have detected an increase of bile acids, sugars, oxidized lipids and oxidized products from arachidonic acid and a decrease of carnitine levels in NETs. MPA/MSEA identified 32 enriched metabolic pathways in NETs related with the TCA cycle and amino acid metabolism. Finally, OPLS-DA and ROC analysis revealed 48 metabolites with diagnostic potential. Conclusions: This study provides, for the first time, a comprehensive metabolic profile of NET patients and identifies a distinctive metabolic signature in plasma of potential clinical use. A reduced set of metabolites of high diagnostic accuracy has been identified. Additionally, new enriched metabolic pathways annotated may open innovative avenues of clinical research.

scholarly journals Intracellular Fate of Universally Labelled 13C Isotopic Tracers of Glucose and Xylose in Central Metabolic Pathways of Xanthomonas oryzae

Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 66 ◽  
Author(s):  
Manu Shree ◽  
Shyam K. Masakapalli
Keyword(s):  
Amino Acids ◽  
Metabolic Pathways ◽  
Metabolic Networks ◽  
Tca Cycle ◽  
Xanthomonas Oryzae ◽  
Flux Analysis ◽  
Isotopic Tracers ◽  
Feeding Experiments ◽  
The Tca Cycle ◽  
Metabolic Route

The goal of this study is to map the metabolic pathways of poorly understood bacterial phytopathogen, Xanthomonas oryzae (Xoo) BXO43 fed with plant mimicking media XOM2 containing glutamate, methionine and either 40% [13C5] xylose or 40% [13C6] glucose. The metabolic networks mapped using the KEGG mapper and the mass isotopomer fragments of proteinogenic amino acids derived from GC-MS provided insights into the activities of Xoo central metabolic pathways. The average 13C in histidine, aspartate and other amino acids confirmed the activities of PPP, the TCA cycle and amino acid biosynthetic routes, respectively. The similar labelling patterns of amino acids (His, Ala, Ser, Val and Gly) from glucose and xylose feeding experiments suggests that PPP would be the main metabolic route in Xoo. Owing to the lack of annotated gene phosphoglucoisomerase in BXO43, the 13C incorporation in alanine could not be attributed to the competing pathways and hence warrants additional positional labelling experiments. The negligible presence of 13C incorporation in methionine brings into question its potential role in metabolism and pathogenicity. The extent of the average 13C labelling in several amino acids highlighted the contribution of pre-existing pools that need to be accounted for in 13C-flux analysis studies. This study provided the first qualitative insights into central carbon metabolic pathway activities in Xoo.

Full The Relationship between Continuous Glucose Monitoring and OGTT in Youth and Young Adults with Cystic Fibrosis

2021 ◽  
Author(s):  
Christine L Chan ◽  
Laura Pyle ◽  
Tim Vigers ◽  
Philip S Zeitler ◽  
Kristen J Nadeau
Keyword(s):  
Cystic Fibrosis ◽  
Continuous Glucose Monitoring ◽  
Cell Function ◽  
Glucose Monitoring ◽  
Oral Glucose ◽  
Β Cell ◽  
Oral Glucose Tolerance Testing ◽  
C Peptide ◽  
Β Cell Function ◽  
The Relationship

Abstract Context Early glucose abnormalities in people with CF (PwCF) are commonly detected by continuous glucose monitoring (CGM). Relationships between these CGM abnormalities and oral glucose tolerance testing (OGTT) in PwCF have not been fully characterized. Objective(s) 1) To determine the relationship between CGM and common OGTT-derived estimates of β-cell function, including C-peptide index and oral disposition index (oDI) and 2) to explore whether CGM can be used to screen for OGTT-defined prediabetes and cystic fibrosis related diabetes (CFRD). Study Design/Methods PwCF not on insulin and healthy controls ages 6-25 yrs were enrolled in a prospective study collecting OGTT and CGM. A subset underwent frequently-sampled OGTTs (fsOGTT) with 7-point glucose, insulin, and C-peptide measurements. Pearson’s correlation coefficient was used to test the association between select CGM and fsOGTT measures. ROC analysis was applied to CGM variables to determine the cutoff optimizing sensitivity and specificity for detecting prediabetes and CFRD. Results A total of 120 participants (controls=35, CF=85), including 69 with fsOGTTs, were included. CGM coefficient of variation correlated inversely with C-peptide index (Cpeptide30-Cpeptide0/Glucose30-Glucose0) (r=-0.45, p<0.001) and oDIcpeptide (C-peptide index)(1/cpep0) (r=-0.48, p<0.0001). In PwCF, CGM variables had ROC-AUCs ranging from 0.43-0.57 for prediabetes and 0.47-0.6 for CFRD. Conclusions Greater glycemic variability on CGM correlated with reduced β-cell function. However, CGM performed poorly at discriminating individuals with and without OGTT-defined CFRD and prediabetes. Prospective studies are now needed to determine how well the different tests predict clinically-relevant non-glycemic outcomes in PwCF.

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.

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