Mechanistic multiscale modelling of energy metabolism in human astrocytes reveals the impact of morphology changes in Alzheimer’s Disease
Fig 1
Spatial arrangement of metabolism has an impact on cellular metabolite concentrations.
A: GLC enters the cytosol of the cell and takes part in glycolysis whose effective kinetics is captured by the two reactions HXK and PYRK. The products of glycolysis are subsequently consumed by the LDH reaction for generating LAC, by the act reaction describing ATP consumption due to cellular activity, and by mitochondria where the effective reaction Mito produces ATP from PYR through the Krebs cycle and oxidative phosphorylation. B: (left) Generic configuration to investigate the effect of metabolite transport on the output of metabolism in a 2D circular domain. The color map highlights the position of the reaction sites (defined by ), which are located on the vertices of an equilateral triangle. Two reaction sites are colocalised at the bottom left corner. (Right) Position of the reaction sites in Arrangement 1: HXK on the top close to the efflux of LAC, PYRK and LDH colocalised close to the GLC influx, and Mito on the last vertex. C: Control scenario: all reaction sites are located in the center. D: Dynamics of the average concentration of each species in Arrangement 1 and Control, compared with the steady-state values from Cloutier et al. [24].