Regulation of the tricarboxylic acid cycle and beta-oxidation by excess substrates.

A simple mathematical model is proposed to explain the inhibition of beta-oxidation and of the tricarboxylic acid cycle by excess of fatty acids. This model is based on the peculiar stoichiometry of beta-oxidation reactions, which accounts for the formation of dynamical traps for free CoA and its esters in the form of 3-ketoacyl-CoA derivatives. It follows from the analysis of the model that the fatty acids can produce 100% inhibition of respiration at some critical concentrations depending on their chain lengths.