A Systems-Level ODE Model of Β-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.