Fig. 6
Possible rescues of CoASH and steady-state mFAO flux in an MCADD model. An MCADD computational mFAO model was simulated at different expression levels of the enzymes identified as possible rescues by metabolic control analysis. The reference value (onefold expression) is given in black. All simulations were performed at 150 µM cytosolic palmitoyl-CoA. The dashed lines in B indicate the Km values of various mitochondrial enzymes that require CoASH as substrate (Table 2). CPT2, VLCAD, SCAD, MTP and ACOT were varied between 20 and 200% of basal expression levels. ACOT was varied by simultaneously increasing the expression of both ACOTs in the model. The inset shows the trajectory of CoASH concentration when VLCAD is incrementally varied with the mitochondrial acetyl-CoA concentration set to 120 µM (lowest value retrieved from literature), compared to the default concentration of 700 µM. A NADH production flux. B Steady-state mitochondrial CoASH