Energy, Entropy and Quantum Tunneling of Protons and Electrons in Brain Mitochondria: Relation to Mitochondrial Impairment in Aging-Related Human Brain Diseases and Therapeutic Measures

摘要: Adult human brains consume a disproportionate amount of energy substrates (2-3% body weight; 20-25% total glucose and oxygen). Adenosine triphosphate (ATP) is universal currency in produced by oxidative phosphorylation (OXPHOS) using ATP synthase, nano-rotor powered the proton gradient generated from proton-coupled electron transfer (PCET) multi-complex transport chain (ETC). ETC catalysis rates are reduced humans with neurodegenerative diseases (NDDs). Declines function NDDs may result combinations nitrative stress (NS)-oxidative (OS) damage; mitochondrial and/or nuclear genomic mutations ETC/OXPHOS genes; epigenetic modifications or defects importation assembly proteins complexes, respectively; alterations dynamics (fusion, fission, mitophagy). Substantial free gained direct O2-mediated oxidation NADH. Traditional mechanisms require separation between O2 electrons flowing NADH/FADH2 through ETC. Quantum tunneling much larger protons facilitate this separation. Neuronal death be viewed as local increase entropy requiring constant input to avoid. The requirement brain partially used for avoidance increase. Mitochondrial therapeutics seeks correct deficiencies OXPHOS.