Antagonistic interaction between oxygenation-linked lactate and CO2 binding to human hemoglobin

Oxygen binding to hemoglobin (Hb) depends on allosteric effectors (CO2, lactate and protons) that may increase drastically in concentration during exercise. The effectors share common binding sites on the Hb molecules, predicting mutual interaction in their effects on Hb (de)oxygenation. We analysed the effects of lactate and CO2, separately and in combination, on O2 binding of purified human Hb at 37 °C and physiological pH and chloride values. We demonstrate pH-dependent, inhibitory interactions between lactate binding and CO2 binding (carbamate formation); at pH 7.4, physiological CO2 tension (∼ 43 mm Hg) reduced lactate binding more markedly (∼ 75%), than lactate (50 mM) inhibited carbamate formation (∼ 25%). In contrast to previous studies on blood and Hb solutions, we moreover find that added lactate neither ‘reverses’ oxylabile carbamate formation (resulting in lower carbamate levels in deoxyHb than in oxyHb) nor exerts greater allosteric effects on Hb–O2 affinity than equal increases in chloride ion concentrations.