title: Modulating hemoglobin nitrite reductase activity through allostery: a mathematical model.
abstract: 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 0.0087M(-1)s(-1) to 0.083M(-1)s(-1).
authors.affiliation: School 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. Electronic address: zrong@essex.ac.uk.
authors.forename: Zimei
authors.initials: Z
authors.lastname: Rong
authors.forename: Abdu I
authors.initials: AI
authors.lastname: Alayash
authors.forename: Michael T
authors.initials: MT
authors.lastname: Wilson
authors.forename: Chris E
authors.initials: CE
authors.lastname: Cooper
mesh_terms: D000494:Allosteric Regulation; D000818:Animals; D004912:Erythrocytes / Q000378:metabolism / Q000502:physiology; D005319:Fetal Hemoglobin / Q000737:chemistry / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008954:Models, Biological; D009569:Nitric Oxide / Q000032:analysis / Q000378:metabolism; D009572:Nitrite Reductases / Q000737:chemistry* / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010108:Oxyhemoglobins / Q000737:chemistry / Q000378:metabolism; D012756:Sheep
chemical_list: D006454:Hemoglobins; D009573:Nitrites; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D005319:Fetal Hemoglobin; D009572:Nitrite Reductases
keywords: Fetal; Hemoglobin; Kinetics; Nitric oxide; Nitrite; Nitrite reductase activity