Reconstruction and flux analysis of coupling between metabolic pathways of astrocytes and neurons: application to cerebral hypoxia

Table 2 Minimum and maximum attainable values for fluxes/flux ratios used in the model to verify the model compared to basal FBA and literature values. The results show that the model with the specified constraints is flexible enough to attain different flux values, but it was the chosen objective functions that resulted in flux values/ratios in accordance with literature. See the results & discussion part of the main text for detailed discussion of FBA results.

% Flux Ratio	minimum	maximum	FBA of resting state*	literature values in percentage
% Lactate release flux (r₁₁) with respect to CMR_glc	0	16	4.5/4.7	3–9 [105-108]
% Glutamate/Glutamine cycle flux (r₇₈) with respect to CMR_glc	0	68	68/56	40–80 [7; 44; 104]
r_TCA,A/r_TCA,total, r₂₂/(r₂₂ + r₅₈) (percent relative oxidative metabolism of astrocytes)	12	42	35/35.4	30^# [7; 97; 100]
% total lipid synthesis with respect to CMR_glc	0.6	3.8	2.8/2.8	2 [74]
% total PPP flux with respect to CMR_glc	0	5.6	5.6/5.6	3–6 [151; 152]
% pyruvate carboxylase flux (r₁₂) with respect to CMR_glc	2.8	45	11.7/10.8	10 [7; 100; 103]

* The second values in this column are results of resting state simulation with 40%–60% partitioning of glucose utilization between neurons and astrocyte respectively, corresponding to glucose uptake rates of 0.128 μmole/g/min and 0.192 μmole/g/min. The results show that the flux ratios are robust to the relative glucose uptake rates by the two cell types.
#The literature value for this percentage is based on experimental results on human [7] and rat [100] as reported in Table 1 and corresponding footnotes of [97]. However, others [156] calculated a lower percentage (19%) for human, based on the same experimental data.

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