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, G. H. Gurtner

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1635-1642
Number of pages8
JournalUnknown Journal
Volume51
Issue number6
DOIs
StatePublished - Jan 1 1981

ASJC Scopus subject areas

  • Physiology
  • Endocrinology

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    Knoblauch, A., Sybert, A., Brennan, N. J., Sylvester, J. T., & Gurtner, G. H. (1981). Effect of hypoxia and CO on a cytochrome P-450 mediated reaction in rabbit lungs. Unknown Journal, 51(6), 1635-1642. https://doi.org/10.1152/jappl.1981.51.6.1635