Biological autoxidation. I. Decontrolled iron: an ultimate carcinogen and toxicant: an hypothesis

Ionic iron at physiological pH hydrolyzes into insoluble aggregates, which disperse on slight acidification. Uncontrolled ionic iron promotes autoxidation, which crosslinks biomolecules and produces destructive activated oxygen. Defenses against autoxidative crosslinking include: 1. ferritin, the macromolecular scavenger of iron; 2. metabolic turnover, which prevents irreversible crosslinking through early catabolic degradation and replacement; and 3. enzymatic deactivation of oxygen. I am proposing that the anticrosslinking defenses are defeated by transient actions of metabolic perturbations, toxicants, oxidants and "foreign bodies", which cause oxidative crosslinking of proteins and lipids into irreversible tissue imprint: indigestible bodies containing porous limited-access spaces (LASs). The pores exclude the macromolecular ferritin and the digestive and antiautoxidation enzymes but admit ionic iron which, sheltered from ferritin, accumulates into decontrolled-iron pathogen (DIP). DIP utilizes the energy of ambient pH fluctuations to erupt from the LAS, swamp the available ferritin, poison the surroundings, catalyze autoxidation and crosslink cell components into additional LAS carriers. With time and sufficient promotion ...Continue Reading