Redox properties of human hemoglobin in complex with fractionated dimeric and polymeric human haptoglobin.

摘要: Haptoglobin (Hp) is an abundant and conserved plasma glycoprotein, which binds acellular adult hemoglobin (Hb) dimers with high affinity facilitates their rapid clearance from circulation after hemolysis. Humans possess three main phenotypes of Hp, designated Hp 1-1, 2-1, 2-2. These variants exhibit diverse structural configurations have been reported to be functionally nonequivalent. We investigated the functional redox properties Hb-Hp complexes prepared using commercially fractionated found that all forms similar behavior. The rate Hb dimer binding occurs bimolecular constants ~0.9 μM(-1) s(-1), irrespective type assayed. Although does accelerate observed HbO2 autoxidation by dissociating tetramers into dimers, for these bound three- fourfold slower than free in solution. Co-incubation ferric any form inhibits heme loss below detectable levels. Intrinsic potentials (E1/2) ferric/ferrous pair each complex are similar, varying +54 +59 mV (vs NHE), essentially same as us previously unfractionated Hp. All generate amounts ferryl exposure hydrogen peroxide. Electron paramagnetic resonance data indicate yields protein-based radicals during this process approximately 4 5% unaffected variant fractions examined equivalent one another respect associated stability result should taken account design phenotype-specific therapeutics aimed at countering Hb-mediated vascular disease.