Modulation of red blood cell oxygen affinity with a novel allosteric modifier of hemoglobin is additive to the Bohr effect.

Journal Article (Journal Article)

PURPOSE: The Bohr effect describes hemoglobin's affinity for oxygen dependent on solution pH. Within pH range 6.0-8.5, hemoglobin's oxygen affinity decreases with decreasing pH. This results in increased oxygen delivery to metabolically active, acidic tissues and improved oxygen uptake in basic regions including lung tissue. Myo-Inositol tripyrophosphate (ITPP) translocates the erythrocyte membrane and allosterically modifies hemoglobin (Hb). We tested the hypothesis that ITPP does not abrogate the Bohr effect. METHODS: Experiments were conducted to determine the effect of increasing concentrations of ITPP on P50 with varying pH. We incubated 10 mL red blood cells at 37 °C for 1 h with ITPP concentrations from 0 to 240 mM. The Clark oxygen electrode (Hemox-Analyzer; TCS Scientific, New Hope, PA) determined oxygen affinity of each sample, in triplicate, using buffers pH 6.8, 7.4, and 7.6. A mixed linear regression model with fixed effects for ITPP concentration and pH was used. RESULTS: Increasing ITPP concentration and decreasing pH increased P50 (p < 0.0001 for ITPP concentration, p < 0.0001 for pH). ITPP modulated increased P50 in normal pH (7.4) and acidic condition pH (6.8); with no effect at alkaline pH (7.6). CONCLUSION: The Bohr effect is conserved, with ITPP augmenting the decreased oxygen affinity seen with tissue acidosis, while not affecting oxygen affinity in conditions similar to a pulmonary microenvironment.

Full Text

Duke Authors

Cited Authors

  • Evans, BA; Ansari, AK; Kamyszek, RW; Salvagno, M; Welsby, J; Fuller, M; Welsby, I

Published Date

  • March 2021

Published In

Volume / Issue

  • 87 /

Start / End Page

  • 102520 -

PubMed ID

  • 33242840

Electronic International Standard Serial Number (EISSN)

  • 1096-0961

Digital Object Identifier (DOI)

  • 10.1016/j.bcmd.2020.102520

Language

  • eng

Conference Location

  • United States