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From Metabolomics to Fluxomics: A Computational Procedure to Translate Metabolite Profiles into Metabolic Fluxes
- Source :
- Biophysical Journal. 108:163-172
- Publication Year :
- 2015
- Publisher :
- Elsevier BV, 2015.
-
Abstract
- We describe a believed-novel procedure for translating metabolite profiles (metabolome) into the set of metabolic fluxes (fluxome) from which they originated. Methodologically, computational modeling is integrated with an analytical platform comprising linear optimization, continuation and dynamic analyses, and metabolic control. The procedure was tested with metabolite profiles obtained from ex vivo mice Langendorff-heart preparations perfused with glucose. The metabolic profiles were analyzed using a detailed kinetic model of the glucose catabolic pathways including glycolysis, pentose phosphate (PP), glycogenolysis, and polyols to translate the glucose metabolome of the heart into the fluxome. After optimization, the ability of the model to simulate the initial metabolite profile was confirmed, and metabolic fluxes as well as the structure of control and regulation of the glucose catabolic network could be calculated. We show that the step catalyzed by phosphofructokinase together with ATP demand and glycogenolysis exert the highest control on the glycolytic flux. The negative flux control exerted by phosphofructokinase on the PP and polyol pathways revealed that the extent of glycolytic flux directly affects flux redirection through these pathways, i.e., the higher the glycolytic flux the lower the PP and polyols. This believed-novel methodological approach represents a step forward that may help in designing therapeutic strategies targeted to diagnose, prevent, and treat metabolic diseases.
- Subjects :
- Polymers
Metabolite
Glycogenolysis
Biophysics
Mice, Transgenic
Pentose phosphate pathway
Biology
Inbred C57BL
Models, Biological
Transgenic
Pentose Phosphate Pathway
Tissue Culture Techniques
Mice
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
Metabolomics
Models
Adenosine Triphosphatases
Animals
Glucose
Glycolysis
Kinetics
Linear Models
Metabolome
Mice, Inbred C57BL
Myocardium
NAD
NADP
Computer Simulation
Fluxomics
030304 developmental biology
Systems Biophysics
0303 health sciences
Biological
Biochemistry
chemistry
Metabolic control analysis
030217 neurology & neurosurgery
Phosphofructokinase
Subjects
Details
- ISSN :
- 00063495
- Volume :
- 108
- Database :
- OpenAIRE
- Journal :
- Biophysical Journal
- Accession number :
- edsair.doi.dedup.....4aa20544201928072aa0cbab3c1477fa