Allosteric effects on oxidative and nitrosative reactions of cell-free hemoglobins.

Published

Journal Article (Review)

A review of the oxidative and nitrosative reactions of cell-free hemoglobin-based oxygen carriers (HBOCs) shows that these reactions are intimately linked and are subject to allosteric control. Cross-linking reactions used to produce HBOCs introduce conformational constraints and result in Hbs with reduced responses to heterotropic and homotropic allosteric effectors. The Nernst plots of heme oxidation of cross-linked HBOCs are shifted to higher potentials relative to unmodified Hb in the absence of allosteric effectors, in accord with their T-state stabilization and right-shifted Hill plots of O(2) binding. They exhibit enhanced rates of autoxidation and nitrite-induced oxidation, features that appear due to their having more solvent-accessible heme pockets. The stability of their NO-Hb derivatives varies as a result of allosteric effects on the extent of formation of pentacoordinate NO-heme geometry by alpha chains and subsequent oxidation of partner beta chains. The physiological implications of these findings on the safety, efficacy and design of second generation HBOCs are discussed in the framework of a reaction scheme showing linkages between Hb-mediated redox reactions. These redox reactions can drive formation of SNO-Hb and other reactive species and are of significance for the use of cell-free Hbs in vivo.

Full Text

Duke Authors

Cited Authors

  • Bonaventura, C; Henkens, R; Alayash, AI; Crumbliss, AL

Published Date

  • August 2007

Published In

Volume / Issue

  • 59 / 8-9

Start / End Page

  • 498 - 505

PubMed ID

  • 17701544

Pubmed Central ID

  • 17701544

Electronic International Standard Serial Number (EISSN)

  • 1521-6551

International Standard Serial Number (ISSN)

  • 1521-6543

Digital Object Identifier (DOI)

  • 10.1080/15216540601188546

Language

  • eng