A Systems-Level ODE Model of B-Oxidation: Algorithmic Flux Optimization and Simulation of MCADD Pathophysiology

We introduce a computational model that simulates β-oxidation under varying metabolic conditions by solving a system of ordinary differential equations (ODEs) that describe the flux of key intermediates and cofactors. The model captures the stepwise breakdown of saturated, even-chain fatty acids, incorporating dynamic cofactor coupling and product drainage via infinite sinks to maintain numerical stability and biological realism. An optimization routine based on Nelder-Mead simplex refines initial conditions to minimize system residuals. When simulating medium-chain acyl-CoA dehydrogenase deficiency (MCADD), the model predicts metabolite accumulation upstream of the enzymatic block and downstream depletion – highlighting the sensitivity of flux distributions to enzymatic constraints. This work frames kinetic modeling as a tractable method to interrogate systems-level metabolic imbalance and offers a modular framework for future expansions.