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

Area of Science:

• Biochemistry
• Physiology
• Molecular Biology

Background:

• Oxygen binding to hemoglobin (Hb) is modulated by allosteric effectors like carbon dioxide (CO2), lactate, and protons.
• These effectors share binding sites on Hb, suggesting potential interactions influencing oxygenation.
• Understanding these interactions is crucial, especially during physiological conditions like exercise when effector concentrations change significantly.

Purpose of the Study:

• To investigate the combined effects of lactate and CO2 on human Hb oxygen binding.
• To analyze the interactions between lactate and CO2 binding sites on Hb.
• To compare the allosteric effects of lactate with those of chloride ions.

Main Methods:

• Purified human hemoglobin was used for experiments.
• Oxygen binding affinity was measured at 37°C under physiological pH and chloride conditions.
• The binding of lactate and CO2 (carbamate formation) was quantified separately and in combination.

Main Results:

• A pH-dependent inhibitory interaction between lactate and CO2 binding was observed.
• At pH 7.4, physiological CO2 tension markedly reduced lactate binding (approx. 75%).
• Lactate (50 mM) showed less inhibition on carbamate formation (approx. 25%).
• Lactate did not reverse oxylabile carbamate formation or show greater allosteric effects than chloride ions.

Conclusions:

• Lactate and CO2 exhibit significant, pH-dependent inhibitory interactions at their shared binding sites on human Hb.
• CO2 exerts a stronger influence on lactate binding than lactate does on CO2 binding under physiological conditions.
• The allosteric impact of lactate on Hb-O2 affinity is comparable to that of chloride ions, differing from previous findings.