Patterns of O2-dependence of metabolism.

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 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 seemingly lost. The advantage of O2 conformity is that it avoids the Pasteur effect; the cost is an exaggerated dependence of mitochondrial respiration on O2 availability. 3. The VO2(max) of man and other low-altitude adapted animals follows the O2 conforming pattern; at altitudes equivalent to the peak of Everest, the VO2(max) is only slightly greater than RMR. Again, key regulatory interactions between the ETS and glycolysis seem to be missing, so the energy deficit is tolerated (lactate production during exercise to exhaustion is less in hypobaric hypoxia than in normoxia). 4. The O2 conformity of VO2(max) in mammals may be explained by inherently inefficient O2 delivery systems in which low Km and low kcat cytochrome oxidase function would be selected. O2-limited maximum mitochondrial respiration helps to explain what would otherwise be a perplexing observation: why over a 10(4) range of mass-specific muscle metabolic rates, the peak O2 uptake rates per unit mitochondrial volume are always the same at VO2(max). 5. The concept of O2-limited mitochondrial respiration predicts that more efficient O2 delivery systems, such as tracheoles found in insect flight muscles, should support much higher in vivo cytochrome oxidase turnover rates. As far as can be currently evaluated, this prediction is realized.(ABSTRACT TRUNCATED AT 250 WORDS)