Genome-Scale Reconstruction of the Human Astrocyte Metabolic Network.
ABSTRACT: Astrocytes 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.
Project description:MartínJiménez2017 - Genome-scale reconstruction of the human astrocyte metabolic network
This model is described in the article:
of the Human Astrocyte Metabolic Network.
Salazar-Barreto D, Barreto GE, González J.
Front Aging Neurosci 2017; 9: 23
Astrocytes 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
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