Int J Med Sci
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For the fist time the mitochondrial process of oxidative phosphorylation has been studied by determining the extent and initial rates of electron flow, H+ translocation, O2 uptake and ATP synthesis under close to in vivo concentrations of oxygen. The following novel results were obtained. 1) The real rates of O2 uptake and ATP synthesis are orders of magnitude higher than those observed under state-3 metabolic conditions. 2) The phosphorylative process of ATP synthesis is neither kinetically nor thermodynamically related to the respiratory process of H+ ejection. 3) The ATP/O stoichiometry is not constant but varies depending on all, the redox potential (DeltaE(h)), the degree of reduction of the membrane and the relative concentrations of O2, ADP, and protein. 4) The free energy of electron flow is not only used for the enzymatic binding and release of substrates and products but fundamentally for the actual synthesis of ATP from ADP and Pi. 5) The concentration of ADP that produces half-maximal responses of ATP synthesis (EC50) is not constant but varies depending on both DeltaE(h) and O2 concentration. 6) The process of ATP synthesis exhibits strong positive catalytic cooperativity with a Hill coefficient, n, of approximately 3.0. It is concluded that the most important factor in determining the extent and rates of ATP synthesis is not the level of ADP or the proton gradient but the concentration of O2 and the state of reduction and/or protonation of the membrane.
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The pathogenesis of neurological diseases and disorders remains mostly unknown. Neuroinflammation has been proposed as a causative factor for neurological diseases. The confirmation that neurogenesis occurs in the adult brain and neural stem cells (NSCs) reside in the adult central nervous system (CNS) of mammals has tremendous implications for our understanding of the physio- and pathology of the nervous system. ⋯ This suggests that adult neurogenesis is involved in the pathogenesis of neurological diseases and disorders, particularly during neuroinflammation. In this manuscript, we will review the modulation of adult neurogenesis in neurological diseases and during neuroinflammation. We will discuss the role and contribution of neuroinflammation and adult neurogenesis to neurological diseases and disorders, and for the therapeutic potential of adult NSCs.