scholarly journals 13C Isotope Labelling to Follow the Flux of Photorespiratory Intermediates

Plants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 427
Author(s):  
Cyril Abadie ◽  
Guillaume Tcherkez
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Isotopic Dilution ◽  
Stoichiometric Coefficient ◽  
Isotope Labelling ◽  
Isotopic Method ◽  
13C Isotope ◽  
Isotopic Analyses ◽  
Endogenous Metabolites ◽  
Co2 Release

Measuring the carbon flux through metabolic pathways in intact illuminated leaves remains challenging because of, e.g., isotopic dilution by endogenous metabolites, the impossibility to reach isotopic steady state, and the occurrence of multiple pools. In the case of photorespiratory intermediates, our knowledge of the partitioning between photorespiratory recycling, storage, and utilization by other pathways is thus rather limited. There has been some controversy as to whether photorespiratory glycine and serine may not be recycled, thus changing the apparent stoichiometric coefficient between photorespiratory O2 fixation and CO2 release. We describe here an isotopic method to trace the fates of glycine, serine and glycerate, taking advantage of positional 13C content with NMR and isotopic analyses by LC–MS. This technique is well-adapted to show that the proportion of glycerate, serine and glycine molecules escaping photorespiratory recycling is very small.

scholarly journals Recent Advances of Microbiome-Associated Metabolomics Profiling in Liver Disease: Principles, Mechanisms, and Applications

2021 ◽  
Vol 22 (3) ◽  
pp. 1160
Author(s):  
Ganesan Raja ◽  
Haripriya Gupta ◽  
Yoseph Asmelash Gebru ◽  
Gi Soo Youn ◽  
Ye Rin Choi ◽  
...  
Keyword(s):  
Liver Disease ◽  
Metabolic Pathways ◽  
High Throughput Screening ◽  
Proof Of Concept ◽  
Metabolic Factors ◽  
Metabolomics Data ◽  
Liver Health ◽  
Activity Screening ◽  
Cellular Microenvironments ◽  
Endogenous Metabolites

Advances in high-throughput screening of metabolic stability in liver and gut microbiota are able to identify and quantify small-molecule metabolites (metabolome) in different cellular microenvironments that are closest to their phenotypes. Metagenomics and metabolomics are largely recognized to be the “-omics” disciplines for clinical therapeutic screening. Here, metabolomics activity screening in liver disease (LD) and gut microbiomes has significantly delivered the integration of metabolomics data (i.e., a set of endogenous metabolites) with metabolic pathways in cellular environments that can be tested for biological functions (i.e., phenotypes). A growing literature in LD and gut microbiomes reports the use of metabolites as therapeutic targets or biomarkers. Although growing evidence connects liver fibrosis, cirrhosis, and hepatocellular carcinoma, the genetic and metabolic factors are still mainly unknown. Herein, we reviewed proof-of-concept mechanisms for metabolomics-based LD and gut microbiotas’ role from several studies (nuclear magnetic resonance, gas/lipid chromatography, spectroscopy coupled with mass spectrometry, and capillary electrophoresis). A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to improve liver health.

scholarly journals Ultra-Performance Liquid Chromatography/Mass Spectrometry-Based Metabolomics for Discovering Potential Biomarkers and Metabolic Pathways of Colorectal Cancer in Mouse Model (ApcMin/+) and Revealing the Effect of Honokiol

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Chen ◽  
Bo-lun Shi ◽  
Run-zhi Qi ◽  
Xing Chang ◽  
Hong-gang Zheng
Keyword(s):  
Colorectal Cancer ◽  
Mouse Model ◽  
Metabolic Pathways ◽  
Molecular Mechanisms ◽  
Tca Cycle ◽  
Ultra Performance Liquid Chromatography ◽  
Therapeutic Effects ◽  
Anticancer Activities ◽  
Metabolic Disturbances ◽  
Endogenous Metabolites

Endogenous metabolites are a class of molecules playing diverse and significant roles in many metabolic pathways for disease. Honokiol (HNK), an active poly-phenolic compound, has shown potent anticancer activities. However, the detailed crucial mechanism regulated by HNK in colorectal cancer remains unclear. In the present study, we investigated the therapeutic effects and the underlying molecular mechanisms of HNK on colorectal cancer in a mouse model (ApcMin/+) by analyzing the urine metabolic profile based on metabolomics, which is a powerful tool for characterizing metabolic disturbances. We found that potential urine biomarkers were involved in the metabolism of compounds such as purines, tyrosines, tryptophans, etc. Moreover, we showed that a total of 27 metabolites were the most contribution biomarkers for intestinal tumors, and we found that the citrate cycle (TCA cycle) was regulated by HNK. In addition, it was suggested that the efficacy of HNK was achieved by affecting the multi-pathway system via influencing relevant metabolic pathways and regulating metabolic function. Our work also showed that high-throughput metabolomics can characterize the regulation of metabolic disorders as a therapeutic strategy to prevent colorectal cancer.

Abstract 241: Acetylomic and Metabolomic Alterations in Aged Hearts: Role for Silent Information Regulator (SIRT) 3

2015 ◽  
Vol 117 (suppl_1) ◽  
Author(s):  
Jimmy Zhang ◽  
William R Urciuoli ◽  
Paul S Brookes ◽  
George A Porter ◽  
Sergiy M Nadtochiy
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Tca Cycle ◽  
Adult Group ◽  
Protein Levels ◽  
Mitochondrial Alterations ◽  
Age Related ◽  
Transport Chain ◽  
Tca Cycle Intermediates ◽  
Substantial Decline

Introduction: SIRT3 is a mitochondrial metabolic regulator, and a decline in function of SIRT3 may play a role in age-related mitochondrial alterations. The aim of this study was to investigate the possible down-regulation of SIRT3 activity in aged hearts, and to identify which metabolic pathways in aged hearts may be impaired due to SIRT3 dysfunction. Methods: Mitochondria were isolated from WT adult (7 mo.), SIRT3 -/- adult (7 mo.) and WT aged (18 mo.) hearts. Acetylated proteins in mitochondrial samples were identified using 2D gels and mass spectrometry. Metabolite concentrations and carbon fluxes through core metabolic pathways were determined using 13 C-labeled substrates and LC-MS/MS. Results: Mitochondrial acetylation patterns in the SIRT3 -/- adult group matched those found in the WT aged group; the level of acetylation was significantly higher than in WT adult. While the SIRT3 -/- samples exhibited zero SIRT3 protein content, no difference in SIRT3 protein level was seen between adult and aged WT hearts. Mechanistically, this suggests that alterations in mitochondrial acetylation during aging were not caused by lower SIRT3 protein levels, but rather by a lower SIRT3 enzymatic activity. Furthermore, aged myocardium exhibited 40% lower NAD + levels, which may underlie compromised SIRT3 activity. ATP levels were decreased in both SIRT3 -/- and WT aged hearts, suggesting possible defects in energy metabolism. Using metabolomics, we demonstrated that alterations of TCA cycle intermediates were similar in SIRT3 -/- and WT aged hearts (relative to WT adult), and included a substantial decline of carbon flux through α-ketoglutarate and malate. Furthermore, regulation of energy production might also be impaired at the level of the electron transport chain, where Complex I was significantly inhibited in both SIRT3 deficient and aged hearts. Conclusions: Collectively these data suggested that acetylomic and metabolomic fingerprints observed in SIRT3 -/- hearts were recapitulated in aged hearts.

scholarly journals Carbon-flux distribution in the central metabolic pathways of Corynebacterium glutamicum during growth on fructose

1998 ◽  
Vol 254 (1) ◽  
pp. 96-102 ◽  
Author(s):  
Helene Dominguez ◽  
Catherine Rollin ◽  
Armel Guyonvarch ◽  
Jean-Luc Guerquin-Kern ◽  
Muriel Cocaign-Bousquet ◽  
...  
Keyword(s):  
Corynebacterium Glutamicum ◽  
Metabolic Pathways ◽  
Carbon Flux ◽  
Flux Distribution ◽  
Carbon Flux Distribution

scholarly journals Metabonomics window into plateau hypoxia

2019 ◽  
Vol 47 (11) ◽  
pp. 5441-5452 ◽  
Author(s):  
Yue Chang ◽  
Wen Zhang ◽  
Kai Chen ◽  
Zhenguo Wang ◽  
Shihai Xia ◽  
...  
Keyword(s):  
High Altitude ◽  
Metabolic Pathways ◽  
Energy Supply ◽  
Oxygen Deficiency ◽  
Future Application ◽  
Altitude Hypoxia ◽  
Quantitative Metabolomics ◽  
Waste Discharge ◽  
Drug Interventions ◽  
Endogenous Metabolites

Oxygen deficiency in the plateau environment weakens aerobic metabolism and reduces the energy supply, leading to high-altitude diseases including decreased circulatory function, decreased nutrient and energy supply to tissues and organs, and decreased waste discharge. The involvement of many metabolic pathways is reflected in dramatic changes in levels of endogenous small molecule metabolites. Metabolomics represents a promising technique for mechanistic studies and drug screening, and metabonomics, or quantitative metabolomics, has been increasingly applied to the study of hypoxic diseases and their pathogenesis, as well as to pharmacodynamics at high altitudes. In this article, we review the recent literature on the pathogenesis of altitude hypoxia and the clinical and preclinical metabonomics of drug interventions. Endogenous metabolites and metabolic pathways change significantly under high-altitude hypoxia. Some drug interventions have also been shown to regulate pathway metabolism, and the problems of applying metabonomics to hypoxic diseases at high altitude and the prospects for its future application are summarized.

scholarly journals Host-bacteria metabolic crosstalk drives S. aureus biofilm

2021 ◽  
Vol 8 (6) ◽  
pp. 106-107
Author(s):  
Kira L. Tomlinson ◽  
Sebastián A. Riquelme
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Immune Cell ◽  
Oxidant Stress ◽  
Bacterial Survival ◽  
Cell Recruitment ◽  
Biofilm Production ◽  
Lung Infections ◽  
Immune Cell Recruitment

Staphylococcus aureus is a prominent pathogen that can cause intractable lung infections in humans. S. aureus persists in the airway despite inflammation and immune cell recruitment by adapting to host-derived antimicrobial factors. A key component of the immune response to infection are host metabolites that regulate inflammation and bacterial survival. In our recent paper (Tomlinson et al., Nat Commun, doi: 10.1038/s41467-021-21718-y), we demonstrated that S. aureus induces the production of the immunoreglatory metabolite itaconate in airway immune cells by stimulating mitochondrial oxidant stress. Itaconate in turn inhibited S. aureus glycolysis and growth, and promoted carbon flux through bacterial metabolic pathways that support biofilm production. These itaconate-induced metabolic changes were recapitulated in a longitudinal series of clinical isolates from a patient with chronic staphylococcal lung infections, demonstrating a role for host immunometabolism in driving bacterial persistence during long-term staphylococcal lung infections.

scholarly journals Rewiring and regulation of cross-compartmentalized metabolism in protists

2010 ◽  
Vol 365 (1541) ◽  
pp. 831-845 ◽  
Author(s):  
Michael L. Ginger ◽  
Geoffrey I. McFadden ◽  
Paul A. M. Michels
Keyword(s):  
Metabolic Pathways ◽  
Carbon Flux ◽  
Isoprenoid Biosynthesis ◽  
Metabolic Diversity ◽  
Unicellular Eukaryotes ◽  
Metabolic Functions ◽  
Pathway Regulation ◽  
Casual Observer ◽  
Anabolic Pathway ◽  
Core Metabolism

Plastid acquisition, endosymbiotic associations, lateral gene transfer, organelle degeneracy or even organelle loss influence metabolic capabilities in many different protists. Thus, metabolic diversity is sculpted through the gain of new metabolic functions and moderation or loss of pathways that are often essential in the majority of eukaryotes. What is perhaps less apparent to the casual observer is that the sub-compartmentalization of ubiquitous pathways has been repeatedly remodelled during eukaryotic evolution, and the textbook pictures of intermediary metabolism established for animals, yeast and plants are not conserved in many protists. Moreover, metabolic remodelling can strongly influence the regulatory mechanisms that control carbon flux through the major metabolic pathways. Here, we provide an overview of how core metabolism has been reorganized in various unicellular eukaryotes, focusing in particular on one near universal catabolic pathway (glycolysis) and one ancient anabolic pathway (isoprenoid biosynthesis). For the example of isoprenoid biosynthesis, the compartmentalization of this process in protists often appears to have been influenced by plastid acquisition and loss, whereas for glycolysis several unexpected modes of compartmentalization have emerged. Significantly, the example of trypanosomatid glycolysis illustrates nicely how mathematical modelling and systems biology can be used to uncover or understand novel modes of pathway regulation.

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