scholarly journals An MIQP framework for metabolic pathways optimisation and dynamic flux analysis

2022 ◽  
pp. 100011
Author(s):  
Lucas Gerken-Starepravo ◽  
Xianfeng Zhu ◽  
Bovinille Anye Cho ◽  
Fernando Vega-Ramon ◽  
Oliver Pennington ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Flux Analysis

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.

scholarly journals Early Perturbations in Glucose Utilization in Malaria-Infected Murine Erythrocytes, Liver and Brain Observed by Metabolomics

Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 277
Author(s):  
Arjun Sengupta ◽  
Soumita Ghosh ◽  
Shobhona Sharma ◽  
Haripalsingh M. Sonawat
Keyword(s):  
Plasmodium Berghei ◽  
Metabolic Pathways ◽  
Malaria Parasite ◽  
Glucose Utilization ◽  
Early Infection ◽  
Flux Analysis ◽  
Plasmodium Berghei Anka ◽  
Central Carbon ◽  
The Brain ◽  
Pathway Level

Investigation of glucose utilization during an infection is central to the study of energy metabolism. The heavy utilization of glucose by the malaria parasite, and the consequences of this process, have been investigated extensively. However, host glucose utilization during early infection has not been explored to date. In a first attempt, this article investigates the changes in the host glucose utilization in Balb/c mice infected with Plasmodium berghei ANKA using 13C-labeled glucose infusion followed by NMR spectroscopy. The results suggested significant alterations of liver, brain and red blood cell (RBC) glucose utilization during early infection when the parasitemia was <1%. At the pathway level, we observed a decrease in the shunt metabolite 2,3-bisphosphoglycerate in the RBCs. Glycolysis and pathways associated with it, along with fatty acid unsaturation, were altered in the liver. Significant changes were observed in the central carbon metabolic pathways in the brain. These results have implications in understanding the host physiology during early infection and pave the way for detailed flux analysis of the proposed perturbed pathways.

scholarly journals Flux Analysis of Central Metabolic Pathways in Geobacter metallireducens during Reduction of Soluble Fe(III)-Nitrilotriacetic Acid

2007 ◽  
Vol 73 (12) ◽  
pp. 3859-3864 ◽  
Author(s):  
Yinjie J. Tang ◽  
Romy Chakraborty ◽  
H�ctor Garc�a Mart�n ◽  
Jeannie Chu ◽  
Terry C. Hazen ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Tricarboxylic Acid Cycle ◽  
Nitrilotriacetic Acid ◽  
Reaction Rates ◽  
Total Carbon ◽  
Exponential Growth Phase ◽  
Flux Analysis ◽  
Metabolic Reaction ◽  
Geobacter Metallireducens ◽  
Terminal Electron Acceptor

ABSTRACT We analyzed the carbon fluxes in the central metabolism of Geobacter metallireducens strain GS-15 using 13C isotopomer modeling. Acetate labeled in the first or second position was the sole carbon source, and Fe-nitrilotriacetic acid was the sole terminal electron acceptor. The measured labeled acetate uptake rate was 21 mmol/g (dry weight)/h in the exponential growth phase. The resulting isotope labeling pattern of amino acids allowed an accurate determination of the in vivo global metabolic reaction rates (fluxes) through the central metabolic pathways using a computational isotopomer model. The tracer experiments showed that G. metallireducens contained complete biosynthesis pathways for essential metabolism, and this strain might also have an unusual isoleucine biosynthesis route (using acetyl coenzyme A and pyruvate as the precursors). The model indicated that over 90% of the acetate was completely oxidized to CO2 via a complete tricarboxylic acid cycle while reducing iron. Pyruvate carboxylase and phosphoenolpyruvate (PEP) carboxykinase were present under these conditions, but enzymes in the glyoxylate shunt and malic enzyme were absent. Gluconeogenesis and the pentose phosphate pathway were mainly employed for biosynthesis and accounted for less than 3% of total carbon consumption. The model also indicated surprisingly high reversibility in the reaction between oxoglutarate and succinate. This step operates close to the thermodynamic equilibrium, possibly because succinate is synthesized via a transferase reaction, and the conversion of oxoglutarate to succinate is a rate-limiting step for carbon metabolism. These findings enable a better understanding of the relationship between genome annotation and extant metabolic pathways in G. metallireducens.

scholarly journals Survival Factors and Metabolic Pathogenesis in Elderly Patients (≥65) With COVID-19: A Multi-Center Study

2021 ◽  
Vol 7 ◽  
Author(s):  
Qi Mei ◽  
Amanda Y. Wang ◽  
Amy Bryant ◽  
Yang Yang ◽  
Ming Li ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multivariate Analysis ◽  
Elderly Patients ◽  
Metabolic Flux Analysis ◽  
Metabolic Pathways ◽  
Odds Ratio ◽  
Metabolic Flux ◽  
Flux Analysis ◽  
Multi Center Study ◽  
Center Study

Background: Elderly patients infected with COVID-19 are reported to be facing a substantially increased risk of mortality. Clinical characteristics, treatment options, and potential survival factors remain under investigation. This study aimed to fill this gap and provide clinically relevant factors associated with survival of elderly patients with COVID-19.Methods: In this multi-center study, elderly patients (age ≥65 years old) with laboratory-confirmed COVID-19 from 4 Wuhan hospitals were included. The clinical end point was hospital discharge or deceased with last date of follow-up on Jul. 08, 2020. Clinical, demographic, and laboratory data were collected. Univariate and multivariate analysis were performed to analyze survival and risk factors. A metabolic flux analysis using a large-scale molecular model was applied to investigate the pathogenesis of SARS-CoV-2 with regard to metabolism pathways.Results: A total of 223 elderly patients infected with COVID-19 were included, 91 (40.8%) were discharged and 132 (59.2%) deceased. Acute respiratory distress syndrome (ARDS) developed in 140 (62.8%) patients, 23 (25.3%) of these patients survived. Multivariate analysis showed that potential risk factors for mortality were elevated D-Dimer (odds ratio: 1.13 [95% CI 1.04 - 1.22], p = 0.005), high immune-related metabolic index (6.42 [95% CI 2.66–15.48], p &lt; 0.001), and increased neutrophil-to-lymphocyte ratio (1.08 [95% 1.03–1.13], p &lt; 0.001). Elderly patients receiving interferon atmotherapy showed an increased probability of survival (0.29 [95% CI 0.17–0.51], p &lt; 0.001). Based on these factors, an algorithm (AlgSurv) was developed to predict survival for elderly patients. The metabolic flux analysis showed that 12 metabolic pathways including phenylalanine (odds ratio: 28.27 [95% CI 10.56–75.72], p &lt; 0.001), fatty acid (15.61 [95% CI 6.66–36.6], p &lt; 0.001), and pyruvate (12.86 [95% CI 5.85–28.28], p &lt; 0.001) showed a consistently lower flux in the survivors vs. the deceased subgroup. This may reflect a key pathogenic mechanism of COVID-19 infection.Conclusion: Several factors such as interferon atmotherapy and recreased activity of specific metabolic pathways were found to be associated with survival of elderly patients. Based on these findings, a survival algorithm (AlgSurv) was developed to assist the clinical stratification for elderly patients. Dysregulation of the metabolic pathways revealed in this study may aid in the drug and vaccine development against COVID-19.

scholarly journals Phosphoketolase Pathway Dominates in Lactobacillus reuteri ATCC 55730 Containing Dual Pathways for Glycolysis

2007 ◽  
Vol 190 (1) ◽  
pp. 206-212 ◽  
Author(s):  
Emma Årsköld ◽  
Elke Lohmeier-Vogel ◽  
Rong Cao ◽  
Stefan Roos ◽  
Peter Rådström ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Metabolic Flux ◽  
Lactobacillus Reuteri ◽  
Intermediate Stage ◽  
Exponential Growth Phase ◽  
Flux Analysis ◽  
Atp Production ◽  
Phosphoketolase Pathway ◽  
Fructose 1,6 Bisphosphate

ABSTRACT Metabolic flux analysis indicated that the heterofermentative Lactobacillus reuteri strain ATCC 55730 uses both the Embden-Meyerhof pathway (EMP) and phosphoketolase pathway (PKP) when glucose or sucrose is converted into the three-carbon intermediate stage of glycolysis. In all cases studied, the main flux is through the PKP, while the EMP is used as a shunt. In the exponential growth phase, 70%, 73%, and 84% of the flux goes through the PKP in cells metabolizing (i) glucose plus fructose, (ii) glucose alone, and (iii) sucrose alone, respectively. Analysis of the genome of L. reuteri ATCC 55730 confirmed the presence of the genes for both pathways. Further evidence for the simultaneous operation of two central carbon metabolic pathways was found through the detection of fructose-1,6-bisphosphate aldolase, phosphofructokinase, and phosphoglucoisomerase activities and the presence of phosphorylated EMP and PKP intermediates using in vitro 31P NMR. The maximum specific growth rate and biomass yield obtained on glucose were twice as low as on sucrose. This was the result of low ATP levels being present in glucose-metabolizing cells, although the ATP production flux was as high as in sucrose-metabolizing cells due to a twofold increase of enzyme activities in both glycolytic pathways. Growth performance on glucose could be improved by adding fructose as an external electron acceptor, suggesting that the observed behavior is due to a redox imbalance causing energy starvation.

scholarly journals Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

2007 ◽  
Vol 4 (1) ◽  
pp. 48 ◽  
Author(s):  
Tunahan Çakιr ◽  
Selma Alsan ◽  
Hale Saybaşιlι ◽  
Ata Akιn ◽  
Kutlu Ö Ülgen
Keyword(s):  
Metabolic Pathways ◽  
Flux Analysis ◽  
Cerebral Hypoxia
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