Oxygen, evolution and redox signalling in the human brain; quantum in the quotidian

Abstract

Abstract: Rising atmospheric oxygen (O 2 ) levels provided a selective pressure for the evolution of O 2 -dependent micro-organisms that began with the autotrophic eukaryotes. Since these primordial times, the respiring mammalian cell has become entirely dependent on the constancy of electron flow, with molecular O 2 serving as the terminal electron acceptor in mitochondrial oxidative phosphorylation. Indeed, the ability to ‘sense’ O 2 and maintain homeostasis is considered one of the most important roles of the central nervous system (CNS) and probably represented a major driving force in the evolution of the human brain. Today, modern humans have evolved with an oversized brain committed to a continually active state and, as a consequence, paradoxically vulnerable to failure if the O 2 supply is interrupted. However, our pre-occupation with O 2 , the elixir of life, obscures the fact that it is a gas with a Janus face, capable of sustaining life in physiologically controlled amounts yet paradoxically deadly to the CNS when in excess. A closer look at its quantum structure reveals precisely why; the triplet ground state diatomic O 2 molecule is paramagnetic and exists in air as a free radical, constrained from reacting aggressively with the brain's organic molecules due to its ‘spin restriction’, a thermodynamic quirk of evolutionary fate. By further exploring O 2 ’s free radical ‘quantum quirkiness’, including emergent (quantum) physiological phenomena, our understanding of precisely how the human brain senses O 2 deprivation (hypoxia) and the elaborate redox-signalling defence mechanisms that defend O 2 homeostasis has the potential to offer unique insights into the pathophysiology and treatment of human brain disease.