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