Abstract
To better understand the dynamic regulation of optimality in metabolic networks
under perturbed conditions, we reconstruct the energetic-metabolic
network in mammalian myocardia using dynamic flux balance analysis
(DFBA). Additionally, we modified the optimal objective from the
maximization of ATP production to the minimal fluctuation of the profile of
metabolite concentration under ischemic conditions, extending the
hypothesis of original minimization of metabolic adjustment to create a
composite modeling approach called M-DFBA. The simulation results
are more consistent with experimental data than are those of the
DFBA model, particularly the retentive predominant contribution of
fatty acid to oxidative ATP synthesis, the exact mechanism of which
has not been elucidated and seems to be unpredictable by the DFBA
model. These results suggest that the systemic states of metabolic
networks do not always remain optimal, but may become suboptimal when a
transient perturbation occurs. This finding supports the relevance of our
hypothesis and could contribute to the further exploration of the
underlying mechanism of dynamic regulation in metabolic networks.
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