Bistability in fatty-acid oxidation resulting from substrate inhibition
Fig 4
A. Modularisation of the mFAO pathway around C4-ketoacyl-CoA into a supply and a demand module. The flux of the supply and the demand module were plotted as a function of a fixed C4-ketoacyl-CoA concentration (B,C). B. Bistability of mFAO arises due to the presence of feedforward substrate inhibition (negative feedforward loop) of C4-acyl-CoA on vMCKATC4 (reaction rate of MCKAT for its C4 substrate) as shown by three steady states of mFAO (S1, S2, and S3) that correspond to three points of intersection between the rates vMCKATC4 and vMSCHADC4 (reaction rate of MSCHAD for its C4 substrate) around C4-ketoacyl-CoA. C. No bistability, but a single steady state as a result of removing the feedforward substrate inhibition (negative feedforward loop) of C4-acyl-CoA from vMCKATC4, corresponding to one point of intersection between the rates vMCKATC4 and vMSCHADC4. All calculations were done at a fixed concentration of 120 μM palmitoyl-CoA.