title: Enhanced nitrite reductase activity associated with the haptoglobin complexed hemoglobin dimer: functional and antioxidative implications.
abstract: The presence of acellular hemoglobin (Hb) within the circulation is generally viewed as a pathological state that can result in toxic consequences. Haptoglobin (Hp), a globular protein found in the plasma, binds with high avidity the αβ dimers derived from the dissociation of Hb tetramer and thus helps clear free Hb. More recently there have been compelling indications that the redox properties of the Hp bound dimer (Hb-Hp) may play a more active role in controlling toxicity by limiting the potential tissue damage caused by propagation of the free-radicals generated within the heme containing globin chains. The present study further examines the potential protective effect of Hp through its impact on the production of nitric oxide (NO) from nitrite through nitrite reductase activity of the Hp bound αβ Hb dimer. The presented results show that the Hb dimer in the Hb-Hp complex has oxygen binding, CO recombination and spectroscopic properties consistent with an Hb species having properties similar to but not exactly the same as the R quaternary state of the Hb tetramer. Consistent with these observations is the finding that the initial nitrite reductase rate for Hb-Hp is approximately ten times that of HbA under the same conditions. These results in conjunction with the earlier redox properties of the Hb-Hp are discussed in terms of limiting the pathophysiological consequences of acellular Hb in the circulation.
authors.affiliation: Department of Physiology and Biophysics, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
authors.forename: Camille J
authors.initials: CJ
authors.lastname: Roche
authors.forename: David
authors.initials: D
authors.lastname: Dantsker
authors.forename: Abdu I
authors.initials: AI
authors.lastname: Alayash
authors.forename: Joel M
authors.initials: JM
authors.lastname: Friedman
mesh_terms: D000042:Absorption; D000975:Antioxidants / Q000737:chemistry* / Q000378:metabolism; D002248:Carbon Monoxide; D006242:Haptoglobins / Q000737:chemistry* / Q000378:metabolism; D006454:Hemoglobins / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D009572:Nitrite Reductases / Q000737:chemistry* / Q000378:metabolism; D010100:Oxygen / Q000737:chemistry / Q000378:metabolism; D010313:Partial Pressure; D010671:Phenylurea Compounds; D013057:Spectrum Analysis
chemical_list: D000975:Antioxidants; D006242:Haptoglobins; D006454:Hemoglobins; D010671:Phenylurea Compounds; C035492:haptoglobin-hemoglobin complex; C064070:L 35; D002248:Carbon Monoxide; D009572:Nitrite Reductases; D010100:Oxygen