Popis: |
It has been suggested12 that the response of tissues to falling [O2] can fall in one of two classes: 1. “regulators”, where VO2 is constant in the face of falling Po, until it is too low to support any ATP production and 2. “conformers”, where VO2 decreases as [O2] decreases without a depletion of ATP. A brief review6 described 3-4 different phases to the metabolic response of a “regulating” cell as [O2] decreases. Initially there may be no change at all. If oxygen supplies are more than adequate then [O2] can decrease to some turnover dependent level without affecting the metabolic state or rate of ATP turnover. The next phase shows no change in VO2 but there is a change in metabolic state as reflected in decreases in the creatine charge ([PCr]/[total creatine], {PCr}) and changes in the cytosolic redox state as glycolysis is recruited. This phase has been documented in isolated mitochondria and supportive evidence seen in intact tissue, especially working muscle19,20,21As the [O2] decreases further, some critical point (PO2crit) is reached where the concentration of oxygen limits the ability of the cell to produce ATP aerobically and the cells is dysoxic. The PO2crit and the PO2 range of dysoxia depends very much on the ATP turnover rate in the cell, being higher at higher turnover rates6. When there is no oxygen available (anoxia) the ATP supply will be severely limited by the capacity to produce ATP from glycolysis and transiently from PCr stores at rates consistent with the ATP consumption. In dysoxia and anoxia the sustainable ATP demand is limited both in rate and in duration. |