Late Breaking Abstract - O2 dissociation curve inflection: hemoglobin's built-in Bohr effect trigger

Recent evidence links the O<sub>2</sub> dissociation curve (ODC) inflection point with the first ventilatory threshold (VT1; Burchert et al., 2023). To investigate this relationship, we reanalyzed 12 high-resolution femoral venous blood data pooled from 5 subjects during rest to heavy 6-minute constant work rate exercise (75% Δ VT1 to maximal O<sub>2</sub> consumption, 265 W; Stringer et al., 1994). Using an established biochemical model of the ODC (Dash et al., 2016), we calculated O<sub>2</sub>, CO<sub>2</sub>, and H<sup>+</sup> dissociation curves from the levels of O<sub>2</sub>, CO<sub>2</sub>, 2,3-DPG, hematocrit, hemoglobin (Hb), pH, and temperature. We identified inflection points through numerical differentiation and root-finding. The first 4 samples showed minimal rightward ODC shift. The 4th sample, collected at the ODC inflection point, revealed that the O<sub>2</sub>, CO<sub>2</sub>, and H<sup>+</sup> dissociation curves reached their inflections simultaneously. At this moment, the H<sup>+</sup> curve intersected and surpassed the CO<sub>2</sub> curve. Thus, at the ODC inflection point, O<sub>2</sub> unloading, CO<sub>2</sub> loading, and H<sup>+</sup> loading of Hb is optimized, with H<sup>+</sup> loading eventually predominating. For the subsequent samples, Hb continued to bind H<sup>+</sup> while unloading CO<sub>2</sub>, causing the CO<sub>2</sub>, and H<sup>+</sup> curves to diverge, thereby activating the Bohr effect and shifting the ODC to the right. We conclude that the activation of the Bohr effect is an emergent property of the ODC triggered at the inflection point due to intricate interactions of O<sub>2</sub>, CO<sub>2</sub> and H<sup>+</sup> with Hb. <fig><object-id>erj;64/suppl_68/PA1677/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

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Published
2024-09-14
DOI
https://doi.org/10.1183/13993003.congress-2024.pa1677
Primary Topic
Hemoglobin structure and function
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article
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article

Late Breaking Abstract - O2 dissociation curve inflection: hemoglobin's built-in Bohr effect trigger

Holger Burchert, Ranjan K. Dash, William W. Stringer
Hemoglobin structure and function
article

Late Breaking Abstract - O2 dissociation curve inflection: hemoglobin's built-in Bohr effect trigger

Holger Burchert, Ranjan K. Dash, William W. Stringer
article en

Abstract

Recent evidence links the O<sub>2</sub> dissociation curve (ODC) inflection point with the first ventilatory threshold (VT1; Burchert et al., 2023). To investigate this relationship, we reanalyzed 12 high-resolution femoral venous blood data pooled from 5 subjects during rest to heavy 6-minute constant work rate exercise (75% Δ VT1 to maximal O<sub>2</sub> consumption, 265 W; Stringer et al., 1994). Using an established biochemical model of the ODC (Dash et al., 2016), we calculated O<sub>2</sub>, CO<sub>2</sub>, and H<sup>+</sup> dissociation curves from the levels of O<sub>2</sub>, CO<sub>2</sub>, 2,3-DPG, hematocrit, hemoglobin (Hb), pH, and temperature. We identified inflection points through numerical differentiation and root-finding. The first 4 samples showed minimal rightward ODC shift. The 4th sample, collected at the ODC inflection point, revealed that the O<sub>2</sub>, CO<sub>2</sub>, and H<sup>+</sup> dissociation curves reached their inflections simultaneously. At this moment, the H<sup>+</sup> curve intersected and surpassed the CO<sub>2</sub> curve. Thus, at the ODC inflection point, O<sub>2</sub> unloading, CO<sub>2</sub> loading, and H<sup>+</sup> loading of Hb is optimized, with H<sup>+</sup> loading eventually predominating. For the subsequent samples, Hb continued to bind H<sup>+</sup> while unloading CO<sub>2</sub>, causing the CO<sub>2</sub>, and H<sup>+</sup> curves to diverge, thereby activating the Bohr effect and shifting the ODC to the right. We conclude that the activation of the Bohr effect is an emergent property of the ODC triggered at the inflection point due to intricate interactions of O<sub>2</sub>, CO<sub>2</sub> and H<sup>+</sup> with Hb. <fig><object-id>erj;64/suppl_68/PA1677/F1</object-id><object-id>F1</object-id><object-id>F1</object-id><graphic></graphic></fig>

University of Basel (CH), Medical College of Wisconsin (US), UCLA Medical Center (US)
Openalex Percentile: Top 80%
Hemoglobin structure and function
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