Hemoglobin Non-equilibrium Oxygen Dissociation Curve

TL;DR

This paper investigates non-equilibrium hemoglobin oxygen dissociation curves, revealing two components of cooperativity—sequential and conformational—that influence oxygen binding under physiological conditions.

Contribution

It introduces a method to determine non-equilibrium ODC and decomposes hemoglobin cooperativity into two distinct components, enhancing understanding of oxygen exchange in tissues.

Findings

Sequential cooperativity accounts for ~70% of Hb cooperativity.

Conformational cooperativity accounts for ~30% of Hb cooperativity.

Non-equilibrium conditions reveal distinct cooperativity components.

Abstract

Abnormal hemoglobins can have major consequences for tissue delivery of oxygen. Correct diagnosis of hemoglobinopathies with altered oxygen affinity requires a determination of hemoglobin oxygen dissociation curve (ODC), which relates the hemoglobin oxygen saturation to the partial pressure of oxygen in the blood. Determination of the ODC of human hemoglobin is typically carried out under conditions in which hemoglobin is in equilibrium with O2 at each partial pressure. However, in the human body due to the fast transit of RBCs through tissues hemoglobin oxygen exchanges occur under non-equilibrium conditions. We describe the determination of non-equilibrium ODC, and show that under these conditions Hb cooperativity has two apparent components in the Adair, Perutz, and MWC models of Hb. The first component, which we call sequential cooperativity, accounts for ~70% of Hb cooperativity, and emerges from the constraint of sequential binding that is shared by the three models. The second component, which we call conformational cooperativity, accounts for ~30% of Hb cooperativity, and is due either to a conformational equilibrium between low affinity and high affinity tetramers (as in the MWC model), or to a conformational change from low to high affinity once two of the tetramer sites are occupied (Perutz model).