Effect of hypoxia and CO on a cytochrome P-450-mediated reaction in rabbit lungs

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Abstract
Evidence indicates that the diffusion of O2 and CO in tissue may be facilitated by a carrier molecule having a P50 that approximates tissue O2 partial pressure (PO2; 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 a control at an estimated tissue PO2 fo 4 Torr (5.5 microM). When inspired CO2 was kept at 200 Torr and inspired CO partial pressure (PCO) varied an estimated tissue PCO/PO2 ratio of 0.025 reduced the reaction rate by 50% of control, but some metabolism persisted at PCO/PO2 ratios larger than one. The relationship between reaction rate and PCO/PO2 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 PO2's.