Journal of Applied Physiology, Vol 51, Issue 6 1635-1642, Copyright © 1981 by American Physiological Society
Effect of hypoxia and CO on a cytochrome P-450-mediated reaction in rabbit lungs
A. Knoblauch, A. Sybert, N. J. Brennan, J. T. Sylvester and G. H. Gurtner
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.
