THE EFFECT OF METHEMOGLOBIN ON THE EQUILIBRIUM BETWEEN OXYGEN AND HEMOGLOBIN

Abstract

In mixtures of met-Hb and ordinary Hb the O2 dissociation curve is shifted to the left as the met-Hb % increases: the shape also becomes progressively less sigmoid and more hyperbolic. The effect is qualitatively the same but quantitatively less than that produced by CO-Hb. The effect has been demonstrated in solns. of ox and human Hb in 0.6 M phosphate with met-Hb made by ferricyanide, aerobic oxidation or nitrite; and in dogs'' whole blood during poisoning with nitrite. The size of the effect is the same over the pH range 6.8 to 7.4 and temp. range 25-37[degree] C. This effect of met-Hb is reversible, as is shown by the return of the dissociation curve to normal when the met-Hb produced in the red cells of the dog by nitrite inj. is completely reduced by the natural enzymic systems of the red cell. The shifts produced by CO-Hb and met-Hb are additive. This newly discovered effect means that in methemoglobinemia the tissues are liable to anoxemia, not only from loss of O2 capacity of the blood, but also from increasing difficulty in the unloading from the blood of such O2 as is available. Methemoglobinemia should therefore receive more attention in industrial conditions and in drug therapy than hitherto. The mechanism of the effect is believed due to the formation of compounds intermediate between reduced Hb (wholly ferrous) and Hb (wholly ferric), the conversion of one or more of the 4 ferrous atoms in the Hb molecule to ferric leading to an increased affinity of the remaining ferrous atoms for O2.