Difference between revisions of "Scrima 2020 bioRxiv"
(Created page with "{{Publication |title=Scrima R, Fugetto S, Capitanio N, Gatti DL (2020) Hemoglobin non-equilibrium oxygen dissociation curve. bioRxiv https://doi.org/10.1101/2020.01.09.900001...") ย |
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|journal=bioRxiv | |journal=bioRxiv | ||
|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 | |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 O<sub>2</sub> 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 โผ70% 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 โผ30% 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). | ||
|keywords=Hemoglobin, Mitochondria, Kinetics, Models | |keywords=Hemoglobin, Mitochondria, Kinetics, Models | ||
|editor=[[Plangger M]], | |editor=[[Plangger M]], | ||
|mipnetlab=IT Foggia Capitanio N | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
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|tissues=Liver | |tissues=Liver | ||
|preparations=Isolated mitochondria | |preparations=Isolated mitochondria | ||
|couplingstates=LEAK | |||
|pathways=S, ROX | |||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
|additional=Labels, 2020-01, | |additional=Labels, 2020-01, | ||
}} | }} |
Revision as of 16:38, 14 January 2020
Scrima R, Fugetto S, Capitanio N, Gatti DL (2020) Hemoglobin non-equilibrium oxygen dissociation curve. bioRxiv https://doi.org/10.1101/2020.01.09.900001 . |
Scrima R, Fugetto S, Capitanio N, Gatti DL (2020) bioRxiv
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 โผ70% 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 โผ30% 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). โข Keywords: Hemoglobin, Mitochondria, Kinetics, Models โข Bioblast editor: Plangger M โข O2k-Network Lab: IT Foggia Capitanio N
Labels: MiParea: Respiration
Organism: Rat
Tissue;cell: Liver
Preparation: Isolated mitochondria
Coupling state: LEAK
Pathway: S, ROX
HRR: Oxygraph-2k
Labels, 2020-01