scholarly journals PathwayAnalyser: A Systems Biology Tool for Flux Analysis of Metabolic Pathways

Author(s):  
Karthik Raman ◽  
Nagasuma Chandra
Metabolites ◽  
2018 ◽  
Vol 8 (4) ◽  
pp. 66 ◽  
Author(s):  
Manu Shree ◽  
Shyam K. Masakapalli

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.


Metabolites ◽  
2020 ◽  
Vol 10 (7) ◽  
pp. 277
Author(s):  
Arjun Sengupta ◽  
Soumita Ghosh ◽  
Shobhona Sharma ◽  
Haripalsingh M. Sonawat

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.


2021 ◽  
Author(s):  
Yi Wang ◽  
Xiaoxia Wang ◽  
Laurence Don Wai Luu ◽  
Shaojin Chen ◽  
Jin Fu ◽  
...  

CoronaVac (Sinovac), an inactivated vaccine for SARS-CoV-2, has been widely used for immunization. However, analysis of the underlying molecular mechanisms driving CoronaVac-induced immunity is still limited. Here, we applied a systems biology approach to understand the mechanisms behind the adaptive immune response to CoronaVac in a cohort of 50 volunteers immunized with 2 doses of CoronaVac. Vaccination with CoronaVac led to an integrated immune response that included several effector arms of the adaptive immune system including specific IgM/IgG, humoral response and other immune response, as well as the innate immune system as shown by complement activation. Metabolites associated with immunity were also identified implicating the role of metabolites in the humoral response, complement activation and other immune response. Networks associated with the TCA cycle and amino acids metabolic pathways, such as phenylalanine metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, and glycine, serine and threonine metabolism were tightly coupled with immunity. Critically, we constructed a multifactorial response network (MRN) to analyze the underlying interactions and compared the signatures affected by CoronaVac immunization and SARS-CoV-2 infection to further identify immune signatures and related metabolic pathways altered by CoronaVac immunization. These results suggest that protective immunity against SARS-CoV-2 can be achieved via multiple mechanisms and highlights the utility of a systems biology approach in defining molecular correlates of protection to vaccination.


F1000Research ◽  
2020 ◽  
Vol 9 ◽  
pp. 288
Author(s):  
Julia Koblitz ◽  
Dietmar Schomburg ◽  
Meina Neumann-Schaal

Metabolic pathways are an important part of systems biology research since they illustrate complex interactions between metabolites, enzymes, and regulators. Pathway maps are drawn to elucidate metabolism or to set data in a metabolic context. We present MetaboMAPS, a web-based platform to visualize numerical data on individual metabolic pathway maps. Metabolic maps can be stored, distributed and downloaded in SVG-format. MetaboMAPS was designed for users without computational background and supports pathway sharing without strict conventions. In addition to existing applications that established standards for well-studied pathways, MetaboMAPS offers a niche for individual, customized pathways beyond common knowledge, supporting ongoing research by creating publication-ready visualizations of experimental data.


2019 ◽  
Vol 12 ◽  
pp. 251686571986968
Author(s):  
Sriram Chandrasekaran

Histone modifications represent an innate cellular mechanism to link nutritional status to gene expression. Metabolites such as acetyl-CoA and S-adenosyl methionine influence gene expression by serving as substrates for modification of histones. Yet, we lack a predictive model for determining histone modification levels based on cellular metabolic state. The numerous metabolic pathways that intersect with histone marks makes it highly challenging to understand their interdependencies. Here, we highlight new systems biology tools to unravel the impact of nutritional cues and metabolic fluxes on histone modifications.


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 ◽  
...  

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.


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