Murburn Concept: A Molecular Explanation for Hormetic and Idiosyncratic Dose Responses

Abstract

Recently, electron transfers and catalyses in a bevy of redox reactions mediated by hemeproteins were explained by murburn concept. The term “murburn” is abstracted from “ mur ed burn ing ” or “ m ild u n r estricted burn ing ” and connotes a novel “ m olecule- u nbound ion– r adical ” interaction paradigm. Quite unlike the genetic regulations and protein-level affinity-based controls that govern order and specificity/selectivity in conventional treatments, murburn concept is based on stochastic/thermodynamic regulatory principles. The novel insight necessitates a “reactivity outside the active-site” perspective, because select redox enzymatic activity is obligatorily mediated via diffusible radical/species. Herein, reactions employing key hemeproteins (as exemplified by CYP2E1) establish direct experimental connection between “additive-influenced redox catalysis” and “unusual dose responses” in reductionist and physiological milieu. Thus, direct and conclusive molecular-level experimental evidence is presented, supporting the mechanistic relevance of murburn concept in “maverick” concentration-based effects brought about by additives. Therefore, murburn concept could potentially explain several physiological hormetic and idiosyncratic dose responses.