The kinetics of the reaction of carbon monoxide with fully oxygenated haemoglobin in solution and erythrocytes

Abstract

SUMMARY1. Spectrophotometric measurements, using a rapid mixing and stopped flow technique, have been made of the rate at which CO displaces 02 from its combination with haemoglobin.2. In haemoglobin solutions, buffered at pH 7-2 and 941, the reaction proceeds by a unimolecular dissociation as proposed by Gibson & Roughton (1955). In a Ringer-Locke solution, equilibrated with a PCo2 of 3 cmHg and at pH 7 4, the reaction of HbO2 with CO is a two-stage process, with a transition from one form of Hb4O6 to another.3. An investigation of the reaction between CO and HbO2 in erythrocytes, suspended in Ringer-Locke solution, indicates that the rate is determined by the chemical reaction and this also is a two-stage process.4. The transition is probably associated with the reaction of CO2 with Hb4O6, following the dissociation from fully saturated oxyhaemoglobin of an oxygen molecule. It alters the relative velocity constants of the reactions of 02 and CO with Hb4O6 by 100: 1.5. The implications of these proposals of the equilibria of haemoglobin with CO and 02 are discussed. The difference between the sigmoid equilibria curves at high HbO2 and HbCO values can be explained as due to the different reaction pathways.

‘Carbon-Monoxide-Releasing Molecule-2 (CORM-2)’ Is a Misnomer: Ruthenium Toxicity, Not CO Release, Accounts for Its Antimicrobial Effects

“…Human haemoglobin has an affinity for CO approximately 200-250 times greater than for oxygen [36,37]. Nevertheless, to assess the potential availability in vivo of a presumptive higher-affinity site for binding of CO from CORM-2, we used neuroglobin (Ngb), which is expressed in brain and retina and has an affinity for CO 500 times higher than haemoglobin.…”

The effect of temperature on the reaction of carbon monoxide with oxygenated haemoglobin.

“…However when this reaction was studied under more physiological conditions, with haemoglobin and erythrocytes in Ringer-Locke solution equilibrated with carbon dioxide, Sirs (1974) found the reaction no longer followed a simple kinetic mechanism. A two stage process was then involved, with the formation of an intermediate complex, and the rate constant, r, was given by Haldane & Smith (1897) only applied, in the presence carbon dioxide, when the oxygen concentration was constant.…”