Nitric oxide binding to human ferrihemoglobins cross-linked between either alpha or beta subunits.

Journal Article (Journal Article)

We have examined the interactions between nitric oxide (NO) and oxidized human hemoglobin, comparing the behavior of unmodified HbA0 with that of two chemically modified hemoglobins. The latter are promising red cell substitute candidates due to their lower oxygen affinity and greater stability as tetramers. The modified forms examined were HbA-DBBF, cross-linked between the alpha chains with bis(3,5-dibromosalicyl) fumarate, and HbA-FMDA, modified between the beta chains with fumaryl monodibromoaspirin. NO binding to the oxidized forms of these hemoglobins is biphasic, due to the differing reactivities of alpha and beta chains. The structural modifications result in altered rate constants for NO binding to both alpha and beta chains. The affinity of the ferric hemes for NO is not correlated with their oxygen affinities in the ferrous state. In a much slower first-order process, the ferric hemes of HbA become reduced. Faster and more heterogeneous kinetics are observed for reduction of the modified hemoglobins. These results may have physiological relevance, since endogenously produced NO is now recognized to play an important role in the relaxation of vascular smooth muscles. If present in vivo, cell-free hemoglobins exposed to NO become rapidly oxidized. Our results show that subsequent interactions of NO with ferrihemoglobin can result in redox cycling. This has the potential of depleting NO and further altering vascular tone with rates dependent on structural parameters of the ferrihemoglobin that are not determined by oxygen affinity.

Full Text

Duke Authors

Cited Authors

  • Alayash, AI; Fratantoni, JC; Bonaventura, C; Bonaventura, J; Cashon, RE

Published Date

  • June 1, 1993

Published In

Volume / Issue

  • 303 / 2

Start / End Page

  • 332 - 338

PubMed ID

  • 8512319

Electronic International Standard Serial Number (EISSN)

  • 1096-0384

International Standard Serial Number (ISSN)

  • 0003-9861

Digital Object Identifier (DOI)

  • 10.1006/abbi.1993.1292


  • eng