Abstract
In hypoxia sensitive cells and tissues, the rates of glucose and O2 consumption are inversely related (Pasteur Effect). Under O2 limiting conditions the demands for glucose (glycogen) in such cells may drastically rise as a means for maintaining ATP turnover close to normoxic rates; nevertheless ion and electrical potentials cannot be sustained due to energy insufficiency and high membrane permeability; metabolic and membrane functions, in effect, are decoupled. ‘Good’ animal anaerobes resolve these problems with a number of biochemical and physiological mechanisms; of these (1) metabolic arrest and (2) stabilized membrane functions are the most effective strategies for extending hypoxia tolerance. Metabolic arrest is achievable by means of a reversed or negative Pasteur Effect (reduced or unchanging glycolytic flux at reduced O2 availability) while coupling of metabolic and membrane function is achievable in spite of the lower energy turnover rates by maintaining membranes of low permeability (probably via reduced densities of ion-specific channels). Although the strategy of combining metabolic arrest with channel arrest has been recognized as a possible intervention, to date success has been minimal, mainly because cold depression of metabolism is the usual arrest mechnism used and this hypothermia in itself perturbs controlled cell function in most endotherms. The only endothermic systems currently known which appear able to use the dual strategy for extending hypoxia tolerance are hypoperfused hypometabolic tissues and organs of diving marine mammals.
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Hochachka, P.W. Metabolic arrest. Intensive Care Med 12, 127–133 (1986). https://doi.org/10.1007/BF00254926
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DOI: https://doi.org/10.1007/BF00254926