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Modulating hemoglobin nitrite reductase activity through allostery: A mathematical model

Rong, Zimei and Alayash, Abdu I and Wilson, Michael T and Cooper, Chris E (2013) 'Modulating hemoglobin nitrite reductase activity through allostery: A mathematical model.' Nitric Oxide, 35. pp. 193-198. ISSN 1089-8603

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The production of nitric oxide by hemoglobin (Hb) has been proposed to play a major role in the control of blood flow. Because of the allosteric nature of hemoglobin, the nitrite reductase activity is a complex function of oxygen partial pressure PO2. We have previous developed a model to obtain the micro rate constants for nitrite reduction by R state (kR) and T state (kT) hemoglobin in terms of the experimental maximal macro rate constant kNmax and the corresponding oxygen concentration PO2max. However, because of the intrinsic difficulty in obtaining accurate macro rate constant kN, from available experiments, we have developed an alternative method to determine the micro reaction rate constants (kR and kT) by fitting the simulated macro reaction rate curve (kN versus PO2) to the experimental data. We then use our model to analyze the effect of pH (Bohr Effect) and blood ageing on the nitrite reductase activity, showing that the fall of bisphosphoglycerate (BPG) during red cell storage leads to increase NO production. Our model can have useful predictive and explanatory power. For example, the previously described enhanced nitrite reductase activity of ovine fetal Hb, in comparison to the adult protein, may be understood in terms of a weaker interaction with BPG and an increase in the value of kT from 0.0087 M-1s -1 to 0.083 M-1s-1. © 2013 Elsevier Inc. All rights reserved.

Item Type: Article
Uncontrolled Keywords: Nitrite; Nitric oxide; Hemoglobin; Nitrite reductase activity; Kinetics; Fetal
Subjects: Q Science > QH Natural history > QH301 Biology
Divisions: Faculty of Science and Health
Faculty of Science and Health > Life Sciences, School of
SWORD Depositor: Elements
Depositing User: Elements
Date Deposited: 20 Dec 2014 22:06
Last Modified: 15 Jan 2022 00:21

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