A rigorously simple quantitative model for free radical behavior in aerobic biological systems.

Background Human life is based on oxygen respiration and an enzymatic, free radical-dependent water chemistry, whose billions of parallel reactions take place at pH ∼7.4 and a temperature of 37°C, in accordance with the laws of chemistry. The cellular metabolic processes occur over time periods covered by the half-lives of ROS (reactive oxygen species) for °OH to over 10 s for LOS (lipid oxygen species), indicating that mixtures of free radicals form the basic components for these processes. Summary and Key Messages The main source of radicals is the mitochondrial conversion of 1-5 % oxygen into "primary" ROS and "secondary" LOS. Every endogenous and exogenous radical generation, triggered by "natural background radiation", "natural environment" or "solar radiation" leads to qualitatively similar mixtures of "primary" ROS and "secondary" LOS or RNS (reactive nitrogen species). A Multilevel Antioxidant Regulation, Repair and Protection System (MARRPS) keeps these radical mixtures in a steady state. Depending on the total number of free radicals, different areas of radical action are defined. The Free Radical Ground State (FRGS) with "homeostasis" and "adaptive homeostasis", the Free Radical Threshold Value (FRTV) and Free Radical Pathological Conditions (FRPC). The quantitative ratio ROS > LOS comprehensively characterizes the "homeostasis" and "adaptive homeostasis" area of the FRGS. The total number of free radicals cannot be measured directly in the "homeostasis" area. "Adaptive homeostasis" is achieved when excess radicals are stable produced beyond "homeostasis" of the FRGS. The quantity that remains controllable in this range is a maximum of ∼3.58 10¹² radicals/mg, the value of the body constant FRTV. The sensitized MARRPS provides "semi-stable homeostatic" states characterized by dual stability with ROS > LOS and a stable total ROS/LOS and RNS count beyond the basal FRGS "homeostasis". If the total number of all radicals exceeds the FRTV, where LOS > ROS, this initiates uncontrolled radical chain reactions. The partial failure of the MARRPS in the FRPC area leads to pathological processes which are the starting point for a hundred different diseases. The design principle described by this simple model applies universally to all aerobic life.