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Modulating hemoglobin nitrite reductase activity through allostery: a mathematical model.

Zimei Rong1, Abdu I Alayash, Michael T Wilson

  • 1School of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK; Centre for English Language Education, The University of Nottingham Ningbo China, 199 Taikang East Road, University Park, Ningbo, Zhejiang 315100, China.

Nitric Oxide : Biology and Chemistry
|November 2, 2013
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Summary

Hemoglobin (Hb) produces nitric oxide (NO) to regulate blood flow. A new model accurately determines Hb

Keywords:
FetalHemoglobinKineticsNitric oxideNitriteNitrite reductase activity

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Area of Science:

  • Biochemistry
  • Physiology
  • Medical Science

Background:

  • Hemoglobin (Hb) is crucial for oxygen transport and blood flow regulation via nitric oxide (NO) production.
  • The nitrite reductase activity of Hb is complex, depending on oxygen partial pressure (PO2) and allosteric states (R and T).
  • Previous models relied on macro rate constants (kN), which are difficult to obtain accurately from experiments.

Purpose of the Study:

  • To develop an alternative method for determining micro reaction rate constants (kR and kT) for nitrite reduction by Hb.
  • To analyze the influence of pH (Bohr Effect) and blood storage (aging) on Hb's nitrite reductase activity.
  • To investigate the enhanced nitrite reductase activity in ovine fetal Hb compared to adult Hb.

Main Methods:

  • Developed a model to determine micro rate constants (kR, kT) from macro rate constants (kNmax, PO2max).
  • Implemented an alternative method fitting simulated macro reaction rate curves (kN vs. PO2) to experimental data.
  • Utilized the model to analyze the effects of pH and bisphosphoglycerate (BPG) levels on NO production.

Main Results:

  • The model accurately determines micro rate constants (kR, kT) by fitting simulated to experimental data.
  • Decreased bisphosphoglycerate (BPG) during red cell storage increases nitric oxide (NO) production.
  • Ovine fetal Hb exhibits enhanced nitrite reductase activity due to weaker BPG interaction and increased kT.

Conclusions:

  • The developed model provides a robust method for determining Hb's micro reaction rate constants.
  • Blood storage conditions, specifically reduced BPG, significantly impact NO production.
  • The model explains variations in Hb nitrite reductase activity, such as in fetal vs. adult Hb.