Inborn Resistance to Hypoxia and the O2-Dependence of Metabolism

Abstract

1. In O2 regulating systems, mitochondrial O2 uptake is stabilized as O2 availability declines by means of metabolite signals that simultaneously activate glycolysis. The consequent Pasteur effect, required to counteract ion leaks, is an attempt to make up the energy deficit arising from O2 limitation. 2. In O2 conforming systems, the regulatory link between the ETS and glycolysis is lost. The advantage of O2 conformity is that it avoids the Pasteur effect which is not required because ion gradients do not dissipate; the cost is reduced reactivity and an exaggerated dependence of mitochondrial respiration on O2 availability. 3. Converting an O2 regulating central nervous system to an O2 conforming one would require “clamping” the phosphate potential during declining O2 availability by a proportionate decline in cell work rates coupled with stabilization of ion gradients across membranes.