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Table 8 Effect of long-chain fatty acids (LCFA) oxidization in the triacarboxylic acid (TCA) cycle over model analysis

From: Exploring metabolism flexibility in complex organisms through quantitative study of precursor sets for system outputs

Main characteristics of models with different ratios of LCFA oxidized in TCA
Model CO2 prediction ATP ATP = 1250 mmol/h/half udder  
     optimum Extreme flux distribution (see Table 9) Variability of AIO coefficients
Ratio of Dataset Predicted Ratio of   Total number Nonplausible Nonplausible Glucose carbon Glucose carbon
long-chain FA   CO2 predicted CO2    flux values AIO required to oxidized
oxidated in TCA    and measured CO2      produce lactose  
0% (HB) 1546 Non available 6628 Nonrelevant hypothesis [2022]    
(CN) 1021 99% 2045 8 6 2 [62.2 ; 72.0] [17.5 ; 28.9]
(Ctrl) 1126 121% 3081 8 6 2 [52.8 ; 62.3] [27.8 ; 39.7]
10% (HB) 1640 Non available 7395 13 13 0 [47.7 ; 62.4] [28.8 ; 45.9]
(CN) 1107 107% 2739 8 6 2 [59.4 ; 72.0] [17.5 ; 32.0]
(Ctrl) 1202 129% 3701 8 6 2 [51.6 ; 62.3] [27.9 ; 41.2]
20% (HB) 1756 Non available 8336 13 13 0 [46.9 ; 62.4] [29.0; 47.0]
(CN) 1214 118% 3607 8 6 2 [57.3 ; 72.0] [17.5 ; 34.6]
(Ctrl) 1298 140% 4476 Nonrelevant hypothesis: predicted CO2 is not compatible with measured CO2 [28]  
25% (HB) 1826 Non available 8396 13 13 0 [46.5; 62.4] [29.0; 47.5]
(CN) 1279 124% 4128 8 6 2 [56.3 ; 72.0] [17.6 ; 35.8]
(Ctrl) 1355 146% 4938 Nonrelevant hypothesis: predicted CO2 is not compatible with measured CO2 [28]  
     ATP balance is too high Extreme distributions are not biologically relevant For plausible ratios of long-chain FA in TCA,(CN) treatment is characterized by a lower proportion of glucose (on a carbon basis) which is oxidized in CO2, and a larger ratio used for lactose synthesis.    
  1. To study the impact of the variability of FA oxidation, a ratio of long-chain FA (10%, 20%, 25%) was introduced in the TCA cycle. For datasets (CN), (Ctrl) and (HB) which were compatible with a given ratio of LCFA oxidation, extreme flux distributions and AIO coefficients variability were studied. Our main conclusions are robust to the introduction of LCFA oxidation (Table 8). Interestingly, as shown in Table 9, the structure of the simplex generated by the (HB) diet is more complicated than the (Ctrl) and (CN) treatments, with 13 vertices for all hypotheses. This is due to the fact that R 15 is highly constrained by measurements, so that this flux cannot vanish when R 14 is optimized or when R 19 is maximized. All the vertices for the (HB)-simplex contradict knowledge-based literature.