Fig. 2
Experimental and simulation data of the mFAO model of wild-type and MCAD-knockout (KO) mouse liver. a Concentrations of mFAO enzymes per mg mitochondrial protein in wild-type (orange bars) and MCAD-KO (purple bars) mouse livers. Data represents median, the box extends from the 25th to 75th percentile and the whiskers extend from the minimum to the maximum value (n = 6). b Total acyl-CoA dehydrogenase (ACAD) activity for substrates of varying carbon chain lengths per mg mitochondrial protein measured in homogenate of isolated mitochondria in wild-type (orange) and MCAD-KO (purple) mouse livers. Data represents median and each individual data point (n = 4). Panels c–f show the dynamic profiles of the Cn-acylcarnitines upon addition of the substrate palmitoylcarnitine (C16; panel c and d) and octanoylcarnitine (C8; panel e and f) to isolated mitochondria of wild-type livers (panel c and e) and MCAD-KO livers (panel d and f) in the presence of the uncoupler FCCP. Symbols represent the data measured (data represents mean ± SEM (n = 6)) and lines represent the simulation after parameter estimation. The color scheme indicated in panel d is similar for panels c–f. Panel g shows the relative change in maximum oxidation rate (flux) normalized to the rate of the wild-type, in experiments (oxygen consumption rate measured during 25 minutes in the presence of FCCP; data represents mean ± SEM (n = 6)) and in dynamic simulations (rate of NADH production by mFAO simulated over the same time period). Panels h and i: Distribution of steady-state flux across the various chain lengths for the mFAO enzymes simulated in the computational model of mouse liver mFAO, for wild-type (panel h) and MCAD-KO (panel i). *P < 0.05, **P < 0.01