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Genome-scale reconstruction of the human astrocyte metabolic network

dc.contributor.authorMartín-Jiménez C.A.
dc.contributor.authorSalazar-Barreto D.
dc.contributor.authorBarreto G.E.
dc.contributor.authorGonzález J.
dc.date.accessioned2020-09-02T22:22:24Z
dc.date.available2020-09-02T22:22:24Z
dc.date.issued2017
dc.identifier10.3389/fnagi.2017.00023
dc.identifier.citation9, FEB, -
dc.identifier.issn16634365
dc.identifier.urihttps://hdl.handle.net/20.500.12728/5225
dc.descriptionAstrocytes are the most abundant cells of the central nervous system; they have a predominant role in maintaining brain metabolism. In this sense, abnormal metabolic states have been found in different neuropathological diseases. Determination of metabolic states of astrocytes is difficult to model using current experimental approaches given the high number of reactions and metabolites present. Thus, genome-scale metabolic networks derived from transcriptomic data can be used as a framework to elucidate how astrocytes modulate human brain metabolic states during normal conditions and in neurodegenerative diseases. We performed a Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network with the purpose of elucidating a significant portion of the metabolic map of the astrocyte. This is the first global high-quality, manually curated metabolic reconstruction network of a human astrocyte. It includes 5,007 metabolites and 5,659 reactions distributed among 8 cell compartments, (extracellular, cytoplasm, mitochondria, endoplasmic reticle, Golgi apparatus, lysosome, peroxisome and nucleus). Using the reconstructed network, the metabolic capabilities of human astrocytes were calculated and compared both in normal and ischemic conditions. We identified reactions activated in these two states, which can be useful for understanding the astrocytic pathways that are affected during brain disease. Additionally, we also showed that the obtained flux distributions in the model, are in accordance with literature-based findings. Up to date, this is the most complete representation of the human astrocyte in terms of inclusion of genes, proteins, reactions and metabolic pathways, being a useful guide for in-silico analysis of several metabolic behaviors of the astrocyte during normal and pathologic states. © 2017 Martín-Jiménez, Salazar-Barreto, Barreto and González.
dc.language.isoen
dc.publisherFrontiers Research Foundation
dc.subjectAstrocyte
dc.subjectGenomic-scale metabolic network
dc.subjectIschemia
dc.subjectModel
dc.subjectSystems biology
dc.subjectacetoacetic acid
dc.subjectadenosine triphosphate
dc.subjectarginine
dc.subjectasparagine
dc.subjectcarbon dioxide
dc.subjectcystine
dc.subjectglucose
dc.subjectglutamic acid
dc.subjectglutamine
dc.subjectglycine
dc.subjecthistidine
dc.subjectisoleucine
dc.subjectleucine
dc.subjectlinoleic acid
dc.subjectlinolenic acid
dc.subjectlysine
dc.subjectmethionine
dc.subjectornithine
dc.subjectoxygen
dc.subjectproline
dc.subjectpyruvic acid
dc.subjectserine
dc.subjectthreonine
dc.subjecttyrosine
dc.subjectvaline
dc.subjectArticle
dc.subjectastrocyte
dc.subjectbrain ischemia
dc.subjectbrain metabolism
dc.subjectbrain mitochondrion
dc.subjectcell nucleus
dc.subjectcytoplasm
dc.subjectendoplasmic reticulum
dc.subjectenergy metabolism
dc.subjectextracellular space
dc.subjectgenomics
dc.subjectGolgi complex
dc.subjecthuman
dc.subjectlysosome
dc.subjectmathematical model
dc.subjectmetabolic rate
dc.subjectmetabolite
dc.subjectperoxisome
dc.titleGenome-scale reconstruction of the human astrocyte metabolic network
dc.typeArticle


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