Reaction of nitrite with human fetal oxyhemoglobin: a model simulation study with implications for blood flow regulation in sickle cell disease (SCD)

Blood Cells, Molecules & Diseases
J M Salhany

Abstract

Nitrite can react in parallel with adult oxy- and deoxy-hemoglobin (HbA), resulting in oxidative denitrosylation of nitrosyl-hemoglobin and rapid dissociation of nitric oxide. Here, simulation studies are presented using a new model to analyze data in the literature comparing the reaction of nitrite with isolated human oxy-HbA, oxy-fetal hemoglobin (oxy-HbF) and oxy-Hb Bart's (a gamma-chain tetramer). The results show that the kinetic constant at the rate-limiting step is 25-fold larger for the reaction of human oxy-HbF, and 63-fold larger for oxy-Hb Bart's both compared to oxy-HbA. This analysis suggests that red cells containing oxy-HbF (F-cells) should have accelerated oxidative denitrosylation. Thus, high levels of HbF present or induced in individuals homozygous for sickle cell disease may serve two functions: (a) the classical function, to directly inhibit polymerization of deoxy sickle hemoglobin, and (b) a novel function, enhanced vasodilation.

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Citations

Feb 7, 2012·Antioxidants & Redox Signaling·Nicoletta CastiglioneFrancesca Cutruzzolà
Oct 11, 2012·Revista brasileira de hematologia e hemoterapia·Romélia Pinheiro Gonçalves
Oct 11, 2012·Revista brasileira de hematologia e hemoterapia·Darcielle Bruna Dias EliasRomélia Pinheiro Gonçalves
Oct 23, 2012·Archives of Medical Research·Bruna Stefânia Carvalho-dos SantosRomélia Pinheiro-Gonçalves
Feb 1, 2011·Nitric Oxide : Biology and Chemistry·Nadiezhda Cantu-MedellinRakesh P Patel
Apr 4, 2014·Chemical Reviews·Luisa B Maia, José J G Moura

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