Reaction of nitrite with human fetal oxyhemoglobin: a model simulation study with implications for blood flow regulation in sickle cell disease (SCD).
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.
Salhany
James M
JM
Departments of Internal Medicine and Biochemistry and Molecular Biology, University of Nebraska Medical Center, 984510 Nebraska Medical Center, Omaha, NE 68198-4510, USA. jamessalhany@gmail.com
D000328:Adult; D000755:Anemia, Sickle Cell / Q000378:metabolism*; D003198:Computer Simulation; D005319:Fetal Hemoglobin / Q000378:metabolism*; D006455:Hemoglobins, Abnormal / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D009573:Nitrites / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000378:metabolism*
D006455:Hemoglobins, Abnormal; D009573:Nitrites; D010108:Oxyhemoglobins; D005319:Fetal Hemoglobin; C030448:hemoglobin Bart's