Induction by Hypoxia of a New Haemoglobin-Like Pigment

Abstract

Substances which bind strongly to cytochrome P-450 change the kinetics of the uptake of oxygen by rat liver slices. The relationship between the respiration rate and ambient P_O2 of liver slices from untreated rats is generally of the form of Michaelis-Menten kinetics. Slices from animals after exposure to piperonyl butoxide, metyropone or diazinon follow Warburg’s equation (Longmuir et al., 1971). The mechanism postulated to explain these findings is that normally the transport of oxygen through tissue is facilitated by cytochrome P-450. When this latter pigment is bound in the oxidized state to certain xenobiotics, it can no longer react with oxygen and facilitate its transport. Since cytochrome P-450 is bound to the endoplasmic reticulum, it cannot act as a mobile carrier as proposed by Wittemberg (1959) but might act as a “bucket brigade” carrier according to Scholander’s model (1960). Curran and Gold (1975) have considered the consequences of partial deletion of carrier in the case of the general model. We have applied a method of partial binding of cytochrome P-450 to determine the effect this has on the kinetics of tissue oxygen uptake as a function of cytochrome P-450 concentration in mice and rats.