Evidence indicates that the difusion of O2 and CO in tissue may be facilitated by a carrier molecule having a P50 that approximates tissue O2 partial pressure (P(O)2; 1-15 Torr) and a much higher affinity for CO than for O2. To determine whether cytochrome P-450 in lung satisfies these criteria, we measured the effect of hypoxia and of CO on the rate of metabolism of the cytochrome P-450 mediated O-demethylation of p-nitroanisole in isolated perfused rabbit lungs. Metabolism was inhibited by 50% of control at an estimated tissue P(O)2 of 4 Torr (5.5 μM). When inspired CO2 was kept at 200 Torr and inspired CO partial pressure (P(CO)) varied an estimated tissue P(CO)/P(O)2 ratio of 0.025 reduced the reaction rate by 50% of control, but some metabolism persisted at P(CO)/P(O)2 ratios larger than one. The relationship between reaction rate and p(CO)/P(O)2 ratio could not be fit by a single value for Haldane constant for M (CO affinity/O2 affinity) but could be described with a two-component model in which metabolism was equally divided between a high-affinity cytochrome (M = 200) and a low-affinity cytochrome (M = 2). These findings suggest that cytochrome P-450 could act as a carrier for O2 and CO in tissue with low P(O)2's.
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