The energetics of cerebral activity critically relies on the functional and
metabolic interactions between neurons and astrocytes. Important open questions
include the relation between neuronal versus astrocytic energy demand, glucose
uptake and intercellular lactate transfer, as well as their dependence on the
level of activity. We have developed a large-scale, constraint-based network
model of the metabolic partnership between astrocytes and glutamatergic neurons
that allows for a quantitative appraisal of the extent to which stoichiometry
alone drives the energetics of the system. We find that the velocity of the
glutamate-glutamine cycle (\$V\_cyc\$) explains part of the uncoupling between
glucose and oxygen utilization at increasing \$V\_cyc\$ levels. Thus, we are
able to characterize different activation states in terms of the tissue
oxygen-glucose index (OGI). Calculations show that glucose is taken up and
metabolized according to cellular energy requirements, and that partitioning of
the sugar between different cell types is not significantly affected by
\$V\_cyc\$. Furthermore, both the direction and magnitude of the lactate shuttle
between neurons and astrocytes turn out to depend on the relative cell glucose
uptake while being roughly independent of \$V\_cyc\$. These findings suggest
that, in absence of ad hoc activity-related constraints on neuronal and
astrocytic metabolism, the glutamate-glutamine cycle does not control the
relative energy demand of neurons and astrocytes, and hence their glucose
uptake and lactate exchange.
%0 Journal Article
%1 Massucci2013Energy
%A Massucci, Francesco A.
%A DiNuzzo, Mauro
%A Giove, Federico
%A Maraviglia, Bruno
%A Castillo, Isaac P.
%A Marinari, Enzo
%A De Martino, Andrea
%D 2013
%J BMC Systems Biology
%K brain metabolism modelling stoichiometric-analysis
%N 1
%P 103+
%R 10.1186/1752-0509-7-103
%T Energy metabolism and glutamate-glutamine cycle in the brain: a stoichiometric modeling perspective
%U http://dx.doi.org/10.1186/1752-0509-7-103
%V 7
%X The energetics of cerebral activity critically relies on the functional and
metabolic interactions between neurons and astrocytes. Important open questions
include the relation between neuronal versus astrocytic energy demand, glucose
uptake and intercellular lactate transfer, as well as their dependence on the
level of activity. We have developed a large-scale, constraint-based network
model of the metabolic partnership between astrocytes and glutamatergic neurons
that allows for a quantitative appraisal of the extent to which stoichiometry
alone drives the energetics of the system. We find that the velocity of the
glutamate-glutamine cycle (\$V\_cyc\$) explains part of the uncoupling between
glucose and oxygen utilization at increasing \$V\_cyc\$ levels. Thus, we are
able to characterize different activation states in terms of the tissue
oxygen-glucose index (OGI). Calculations show that glucose is taken up and
metabolized according to cellular energy requirements, and that partitioning of
the sugar between different cell types is not significantly affected by
\$V\_cyc\$. Furthermore, both the direction and magnitude of the lactate shuttle
between neurons and astrocytes turn out to depend on the relative cell glucose
uptake while being roughly independent of \$V\_cyc\$. These findings suggest
that, in absence of ad hoc activity-related constraints on neuronal and
astrocytic metabolism, the glutamate-glutamine cycle does not control the
relative energy demand of neurons and astrocytes, and hence their glucose
uptake and lactate exchange.
@article{Massucci2013Energy,
abstract = {The energetics of cerebral activity critically relies on the functional and
metabolic interactions between neurons and astrocytes. Important open questions
include the relation between neuronal versus astrocytic energy demand, glucose
uptake and intercellular lactate transfer, as well as their dependence on the
level of activity. We have developed a large-scale, constraint-based network
model of the metabolic partnership between astrocytes and glutamatergic neurons
that allows for a quantitative appraisal of the extent to which stoichiometry
alone drives the energetics of the system. We find that the velocity of the
glutamate-glutamine cycle (\$V\_{cyc}\$) explains part of the uncoupling between
glucose and oxygen utilization at increasing \$V\_{cyc}\$ levels. Thus, we are
able to characterize different activation states in terms of the tissue
oxygen-glucose index (OGI). Calculations show that glucose is taken up and
metabolized according to cellular energy requirements, and that partitioning of
the sugar between different cell types is not significantly affected by
\$V\_{cyc}\$. Furthermore, both the direction and magnitude of the lactate shuttle
between neurons and astrocytes turn out to depend on the relative cell glucose
uptake while being roughly independent of \$V\_{cyc}\$. These findings suggest
that, in absence of ad hoc activity-related constraints on neuronal and
astrocytic metabolism, the glutamate-glutamine cycle does not control the
relative energy demand of neurons and astrocytes, and hence their glucose
uptake and lactate exchange.},
added-at = {2018-12-02T16:09:07.000+0100},
archiveprefix = {arXiv},
author = {Massucci, Francesco A. and DiNuzzo, Mauro and Giove, Federico and Maraviglia, Bruno and Castillo, Isaac P. and Marinari, Enzo and De Martino, Andrea},
biburl = {https://www.bibsonomy.org/bibtex/27430f999f08bdd0fc671274a95d9e833/karthikraman},
citeulike-article-id = {12715592},
citeulike-linkout-0 = {http://arxiv.org/abs/1310.6556},
citeulike-linkout-1 = {http://arxiv.org/pdf/1310.6556},
citeulike-linkout-2 = {http://dx.doi.org/10.1186/1752-0509-7-103},
day = 24,
doi = {10.1186/1752-0509-7-103},
eprint = {1310.6556},
interhash = {99f80eef5d4e650fe2150413a6483690},
intrahash = {7430f999f08bdd0fc671274a95d9e833},
issn = {1752-0509},
journal = {BMC Systems Biology},
keywords = {brain metabolism modelling stoichiometric-analysis},
month = oct,
number = 1,
pages = {103+},
posted-at = {2013-10-11 05:13:39},
priority = {2},
timestamp = {2018-12-02T16:09:07.000+0100},
title = {Energy metabolism and glutamate-glutamine cycle in the brain: a stoichiometric modeling perspective},
url = {http://dx.doi.org/10.1186/1752-0509-7-103},
volume = 7,
year = 2013
}