The TCA Stall Model: A Systems Description of the Non-Responder Phenotype via Redox Congestion

This preprint introduces the Redox–Kernel Carbon–Flux (RKCF) attractor as a low-dimensional state description of metabolic phenotype, with fast state A(t) = (x(t), y(t)) coupling (i) redox-kernel dischargeability and (ii) carbon-handling commitment (CO₂ completion vs export/storage). As a concrete mechanistic instantiation, it develops the TCA Stall Model: under sustained substrate influx with low ADP demand, elevated proton-motive force and Q-pool over-reduction constrain effective electron throughput, promote RET/ROS, limit functional NAD⁺ access, and impose SDH back-pressure. This shifts the succinate:αKG balance, linking normoxic redox congestion to αKG-dependent dioxygenase inhibition, HIF-1α pseudohypoxic signalling, and stabilization of a glycolytic, low-plasticity program despite preserved oxygen availability. A central consequence is a coupled shift in carbon fate: reduced CO₂ completion with increased overflow/export as lactate, succinate, and citrate, with muscle-centred initiation and system-level propagation via circulating intermediates. Within the RKCF framing, “non-responders” emerge as trajectories trapped in a stall-biased basin: interventions may increase nominal downstream capacity, yet fail to restore redox-kernel discharge or CO₂ completion, and therefore do not move A(t) into a high-plasticity regime. This reframes non-response as a constraint and state-space problem rather than a dose or compliance issue. The manuscript provides a vector taxonomy (geometry, kernel–flux, field, restorative) and outlines falsifiable, in vivo testable predictions and a minimal evaluation strategy. This work is a systems/mechanistic framework and does not constitute clinical guidance.