The role of oxygen in metabolic regulation

Abstract

1. Under ordinary conditions the rate of energy metabolism in cells is governed by the ADP-feedback system, since the other reactants (inorganic phosphate, substrate, oxygen, enzymes and co-factors) are present in relative excess. 2. When the supply of oxygen is severely limited, it may assume the characteristics of a rate-limiter, and the pattern as well as the rate of metabolism may be altered. 3. The quantitative estimation of the severity of hypoxia is a more difficult problem than is generally realized. The available approaches include: direct measurement of tissue (perhaps intracellular) oxygen tension with micro-electrodes, measurement of the oxidation-reduction status of cells in terms of the ratios of oxidized and reduced forms of electron carrier components (e. g. NAD : NADH2), measurement of the concentrations of high energy compounds in the tissues, and measurement of the "excess lactate" concentration of tissues. The results of these various methods are not always in agreement, and the cause of this lack of agreement is an important problem to be solved. 4. Other important unsolved problems in this field are the relation between intracellular oxygen tension and the partition of ATP-formation between aerobic and anaerobic pathways, and the possible conservation of limited supplies of ATP by its selective utilization for those functions essential for cell survival. 5. Adaptation to chronic hypoxia may involve systemic adjustments which increase the delivery of oxygen to the cells, and cellular adjustments which enable the cells to survive a decrease in their oxygen supply. The occurrence of the systemic adjustments is well established, but the occurrence of cellular adjustments is controversial. 6. It may be concluded that oxygen tension becomes a metabolic regulator only when the intracellular oxygen tension falls to very low levels indeed. 7. The responses of the cells to this condition of severe oxygen deficiency may include: (a) adaptive enzyme changes which permit more efficient utilization of the available oxygen, (b) increased contribution of anaerobic metabolism, and (c) selective utilization of the available energy supply for those functions which are most essential for the survival of the cells. © 1966 Biologischen Anstalt Helgoland.