Biochemical Competition Makes Fatty-Acid β-Oxidation Vulnerable to Substrate Overload
Figure 1
Schematic overview of FA β-oxidation as it is modeled in this study.
Enzymes are depicted in italics bold face, metabolites in regular and allosteric inhibitors in red. CPT1: carnitine-palmitoyl transferase 1 (E.C. 2.3.1.21), CACT: carnitine-acyl-carnitine translocase, CPT2: carnitine-palmitoyl transferase 2 (E.C. 2.3.1.21), VLCAD: very-long-chain acyl-CoA dehydrogenase (E.C. 1.3.99.3), LCAD: long-chain acyl-CoA dehydrogenase (E.C. 1.3.99.3), MCAD: medium-chain acyl-CoA dehydrogenase (E.C. 1.3.99.3), SCAD short-chain acyl-CoA dehydrogenase (E.C.1.3.8.1 for butanoyl CoA (C4) (was previously E.C. 1.3.99.2) and E.C. 1.3.99.3 for hexanoyl CoA (C6)), MTP: mitochondrial trifunctional protein (E.C. 4.2.1.17, E.C. 1.1.1.211 and E.C. 2.3.1.16), M/SCHAD: medium/short-chain hydroxyacyl-CoA dehydrogenase (E.C. 1.1.1.35), MCKAT: medium-chain ketoacyl-CoA thiolase (E.C. 2.3.1.16). The chain-length specificity as included in the model is indicated for each enzyme (e.g. C6–C12). The boundary metabolites which are kept at fixed concentrations are underlined. The direction of the flux is from the small to large arrow heads.