Quantitative evaluation of respiration induced metabolic oscillations in erythrocytes

Bjørn Hald; Mads F Madsen; Sune Danø; Bjørn Quistorff; Preben G Sørensen

doi:10.1016/j.bpc.2008.12.008

Quantitative evaluation of respiration induced metabolic oscillations in erythrocytes

Bjørn Hald, Mads F Madsen, Sune Danø, Bjørn Quistorff, Preben G Sørensen

7 Citations (Scopus)

Abstract

The changes in the partial pressures of oxygen and carbon dioxide (P(O(2)) and P(CO(2))) during blood circulation alter erythrocyte metabolism, hereby causing flux changes between oxygenated and deoxygenated blood. In the study we have modeled this effect by extending the comprehensive kinetic model by Mulquiney and Kuchel [P.J. Mulquiney, and P.W. Kuchel. Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement, Biochem. J. 1999, 342, 581-596.] with a kinetic model of hemoglobin oxy-/deoxygenation transition based on an oxygen dissociation model developed by Dash and Bassingthwaighte [R. Dash, and J. Bassingthwaighte. Blood HbO(2) and HbCO(2) dissociation curves at varied O(2), CO(2), pH, 2,3-DPG and temperature levels, Ann. Biomed. Eng., 2004, 32(12), 1676-1693.]. The system has been studied during transitions from the arterial to the venous phases by simply forcing P(O(2)) and P(CO(2)) to follow the physiological values of venous and arterial blood. The investigations show that the system passively follows a limit cycle driven by the forced oscillations of P(O(2)) and is thus inadequately described solely by steady state consideration. The metabolic system exhibits a broad distribution of time scales. Relaxations of modes with hemoglobin and Mg(2+) binding reactions are very fast, while modes involving glycolytic, membrane transport and 2,3-BPG shunt reactions are much slower. Incomplete slow mode relaxations during the 60 s period of the forced transitions cause significant overshoots of important fluxes and metabolite concentrations - notably ATP, 2,3-BPG, and Mg(2+). The overshoot phenomenon arises in consequence of a periodical forcing and is likely to be widespread in nature - warranting a special consideration for relevant systems.

Original language	English
Journal	Biophysical Chemistry
Volume	141
Issue number	1
Pages (from-to)	41-8
Number of pages	7
ISSN	0301-4622
DOIs	https://doi.org/10.1016/j.bpc.2008.12.008
Publication status	Published - 2009

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10.1016/j.bpc.2008.12.008

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@article{23185790566f11de87b8000ea68e967b,

title = "Quantitative evaluation of respiration induced metabolic oscillations in erythrocytes",

abstract = "The changes in the partial pressures of oxygen and carbon dioxide (P(O(2)) and P(CO(2))) during blood circulation alter erythrocyte metabolism, hereby causing flux changes between oxygenated and deoxygenated blood. In the study we have modeled this effect by extending the comprehensive kinetic model by Mulquiney and Kuchel [P.J. Mulquiney, and P.W. Kuchel. Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement, Biochem. J. 1999, 342, 581-596.] with a kinetic model of hemoglobin oxy-/deoxygenation transition based on an oxygen dissociation model developed by Dash and Bassingthwaighte [R. Dash, and J. Bassingthwaighte. Blood HbO(2) and HbCO(2) dissociation curves at varied O(2), CO(2), pH, 2,3-DPG and temperature levels, Ann. Biomed. Eng., 2004, 32(12), 1676-1693.]. The system has been studied during transitions from the arterial to the venous phases by simply forcing P(O(2)) and P(CO(2)) to follow the physiological values of venous and arterial blood. The investigations show that the system passively follows a limit cycle driven by the forced oscillations of P(O(2)) and is thus inadequately described solely by steady state consideration. The metabolic system exhibits a broad distribution of time scales. Relaxations of modes with hemoglobin and Mg(2+) binding reactions are very fast, while modes involving glycolytic, membrane transport and 2,3-BPG shunt reactions are much slower. Incomplete slow mode relaxations during the 60 s period of the forced transitions cause significant overshoots of important fluxes and metabolite concentrations - notably ATP, 2,3-BPG, and Mg(2+). The overshoot phenomenon arises in consequence of a periodical forcing and is likely to be widespread in nature - warranting a special consideration for relevant systems.",

author = "Bj{\o}rn Hald and Madsen, {Mads F} and Sune Dan{\o} and Bj{\o}rn Quistorff and S{\o}rensen, {Preben G}",

note = "Keywords: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Arteries; Blood Circulation; Carbon Dioxide; Cell Respiration; Erythrocytes; Glycolysis; Hemoglobins; Humans; Hydrogen-Ion Concentration; Kinetics; Magnesium; Models, Biological; Oxygen; Partial Pressure; Veins",

year = "2009",

doi = "10.1016/j.bpc.2008.12.008",

language = "English",

volume = "141",

pages = "41--8",

journal = "Biophysical Chemistry",

issn = "0301-4622",

publisher = "Elsevier",

number = "1",

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T1 - Quantitative evaluation of respiration induced metabolic oscillations in erythrocytes

AU - Hald, Bjørn

AU - Madsen, Mads F

AU - Danø, Sune

AU - Quistorff, Bjørn

AU - Sørensen, Preben G

N1 - Keywords: 2,3-Diphosphoglycerate; Adenosine Triphosphate; Arteries; Blood Circulation; Carbon Dioxide; Cell Respiration; Erythrocytes; Glycolysis; Hemoglobins; Humans; Hydrogen-Ion Concentration; Kinetics; Magnesium; Models, Biological; Oxygen; Partial Pressure; Veins

PY - 2009

Y1 - 2009

N2 - The changes in the partial pressures of oxygen and carbon dioxide (P(O(2)) and P(CO(2))) during blood circulation alter erythrocyte metabolism, hereby causing flux changes between oxygenated and deoxygenated blood. In the study we have modeled this effect by extending the comprehensive kinetic model by Mulquiney and Kuchel [P.J. Mulquiney, and P.W. Kuchel. Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement, Biochem. J. 1999, 342, 581-596.] with a kinetic model of hemoglobin oxy-/deoxygenation transition based on an oxygen dissociation model developed by Dash and Bassingthwaighte [R. Dash, and J. Bassingthwaighte. Blood HbO(2) and HbCO(2) dissociation curves at varied O(2), CO(2), pH, 2,3-DPG and temperature levels, Ann. Biomed. Eng., 2004, 32(12), 1676-1693.]. The system has been studied during transitions from the arterial to the venous phases by simply forcing P(O(2)) and P(CO(2)) to follow the physiological values of venous and arterial blood. The investigations show that the system passively follows a limit cycle driven by the forced oscillations of P(O(2)) and is thus inadequately described solely by steady state consideration. The metabolic system exhibits a broad distribution of time scales. Relaxations of modes with hemoglobin and Mg(2+) binding reactions are very fast, while modes involving glycolytic, membrane transport and 2,3-BPG shunt reactions are much slower. Incomplete slow mode relaxations during the 60 s period of the forced transitions cause significant overshoots of important fluxes and metabolite concentrations - notably ATP, 2,3-BPG, and Mg(2+). The overshoot phenomenon arises in consequence of a periodical forcing and is likely to be widespread in nature - warranting a special consideration for relevant systems.

AB - The changes in the partial pressures of oxygen and carbon dioxide (P(O(2)) and P(CO(2))) during blood circulation alter erythrocyte metabolism, hereby causing flux changes between oxygenated and deoxygenated blood. In the study we have modeled this effect by extending the comprehensive kinetic model by Mulquiney and Kuchel [P.J. Mulquiney, and P.W. Kuchel. Model of 2,3-bisphosphoglycerate metabolism in the human erythrocyte based on detailed enzyme kinetic equations: equations and parameter refinement, Biochem. J. 1999, 342, 581-596.] with a kinetic model of hemoglobin oxy-/deoxygenation transition based on an oxygen dissociation model developed by Dash and Bassingthwaighte [R. Dash, and J. Bassingthwaighte. Blood HbO(2) and HbCO(2) dissociation curves at varied O(2), CO(2), pH, 2,3-DPG and temperature levels, Ann. Biomed. Eng., 2004, 32(12), 1676-1693.]. The system has been studied during transitions from the arterial to the venous phases by simply forcing P(O(2)) and P(CO(2)) to follow the physiological values of venous and arterial blood. The investigations show that the system passively follows a limit cycle driven by the forced oscillations of P(O(2)) and is thus inadequately described solely by steady state consideration. The metabolic system exhibits a broad distribution of time scales. Relaxations of modes with hemoglobin and Mg(2+) binding reactions are very fast, while modes involving glycolytic, membrane transport and 2,3-BPG shunt reactions are much slower. Incomplete slow mode relaxations during the 60 s period of the forced transitions cause significant overshoots of important fluxes and metabolite concentrations - notably ATP, 2,3-BPG, and Mg(2+). The overshoot phenomenon arises in consequence of a periodical forcing and is likely to be widespread in nature - warranting a special consideration for relevant systems.

U2 - 10.1016/j.bpc.2008.12.008

DO - 10.1016/j.bpc.2008.12.008

M3 - Journal article

C2 - 19162390

SN - 0301-4622

VL - 141

SP - 41

EP - 48

JO - Biophysical Chemistry

JF - Biophysical Chemistry

IS - 1

ER -

Quantitative evaluation of respiration induced metabolic oscillations in erythrocytes

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