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Nitric oxide generation from heme/copper assembly mediated nitrite reductase activity

  • Shabnam Hematian
  • Maxime A. Siegler
  • Kenneth D. KarlinEmail author
Original Paper
Part of the following topical collections:
  1. Topical Issue in honor of Ivano Bertini

Abstract

Nitric oxide (NO) as a cellular signaling molecule and vasodilator regulates a range of physiological and pathological processes. Nitrite (NO2 ) is recycled in vivo to generate nitric oxide, particularly in physiologic hypoxia and ischemia. The cytochrome c oxidase binuclear heme a 3/CuB active site is one entity known to be responsible for conversion of cellular nitrite to nitric oxide. We recently reported that a partially reduced heme/copper assembly reduces nitrite ion, producing nitric oxide; the heme serves as the reductant and the cupric ion provides a Lewis acid interaction with nitrite, facilitating nitrite (N–O) bond cleavage (Hematian et al., J. Am. Chem. Soc. 134:18912–18915, 2012). To further investigate this nitrite reductase chemistry, copper(II)–nitrito complexes with tridentate and tetradentate ligands were used in this study, where either O,O′-bidentate or O-unidentate modes of nitrite binding to the cupric center are present. To study the role of the reducing ability of the ferrous heme center, two different tetraarylporphyrinate–iron(II) complexes, one with electron-donating para-methoxy peripheral substituents and the other with electron-withdrawing 2,6-difluorophenyl substituents, were used. The results show that differing modes of nitrite coordination to the copper(II) ion lead to differing kinetic behavior. Here, also, the ferrous heme is in all cases the source of the reducing equivalent required to convert nitrite to nitric oxide, but the reduction ability of the heme center does not play a key role in the observed overall reaction rate. On the basis of our observations, reaction mechanisms are proposed and discussed in terms of heme/copper heterobinuclear structures.

Keywords

Nitric oxide Model compounds Nitrite reductase Nitrite coordination modes Cytochrome c oxidase 

Notes

Acknowledgments

We are grateful to the US National Institutes of Health for support of this research (GM60353).

Supplementary material

775_2013_1081_MOESM1_ESM.pdf (1.1 mb)
Supplementary material 1 (PDF 1135 kb)

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Copyright information

© SBIC 2014

Authors and Affiliations

  • Shabnam Hematian
    • 1
  • Maxime A. Siegler
    • 1
  • Kenneth D. Karlin
    • 1
    Email author
  1. 1.Department of ChemistryJohns Hopkins UniversityBaltimoreUSA

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