Biochemical Competition Makes Fatty-Acid β-Oxidation Vulnerable to Substrate Overload
Figure 2
Comparison between the model simulations and the experiment with palmitoyl CoA as substrate.
At time point zero the substrate palmitoyl CoA was added to uncoupled mitochondria in the presence of an excess amount of l-carnitine and malic acid. Samples for acyl carnitine analysis were taken at different time points. Error bars on the experimental data represent SEM (n = 4 for the flux data, n = 8 for the acyl-carnitine concentrations). Panel A: Comparison of the experimental and modeled flux through the FA β-oxidation. The reported experimental flux is 2/3 of the oxygen consumption flux averaged from 1.5 to 8 min. The modeled flux equals the production fluxes of NADH plus FADH2 divided by 2 (one O2 oxidizes two NADH or FADH2), averaged over the same time interval. Panel B: experimental acyl-carnitine concentrations in total samples, i.e. including intra- and extramitochondrial metabolites. Panel C: acyl-carnitine concentrations simulated by the computer model, representing the weighted average over the matrix and extramitochondrial concentrations to allow direct comparison to the experiments.