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Nitric oxide interactions with cobalamins: biochemical and functional consequences.

Publication ,  Journal Article
Brouwer, M; Chamulitrat, W; Ferruzzi, G; Sauls, DL; Weinberg, JB
Published in: Blood
September 1, 1996

Nitric oxide (NO) is a paramagnetic gas that has been implicated in a wide range of biologic functions. The common pathway to evoke the functional response frequently involves the formation of an iron-nitrosyl complex in a target (heme) protein. In this study, we report on the interactions between NO and cobalt-containing vitamin B12 derivatives. Absorption spectroscopy showed that of the four Co(III) derivatives (cyanocobalamin [CN-Cbl], aquocobalamin [H2O-Cbl], adenosylcobalamin [Ado-Cbl], and methylcobalamin [MeCbl]), only the H2O-Cbl combined with NO. In addition, electron paramagnetic resonance spectroscopy of H2O-Cbl preparations showed the presence of a small amount of Cob-(II)alamin that was capable of combining with NO. The Co(III)-NO complex was very stable, but could transfer its NO moiety to hemoglobin (Hb). The transfer was accompanied by a reduction of the Co(III) to Co(II), indicating that NO+ (nitrosonium) was the leaving group. In accordance with this, the NO did not combine with the Hb Fe(II)-heme, but most likely with the Hb cysteine-thiolate. Similarly, the Co(III)-NO complex was capable of transferring its NO to glutathione. Ado-Cbl and Me-Cbl were susceptible to photolysis, but CN-Cbl and H2O-Cbl were not. The homolytic cleavage of the Co(III)-Ado or Co(III)-Me bond resulted in the reduction of the metal. When photolysis was performed in the presence of NO, formation of NO-Co(II) was observed. Co(II)-nitrosyl oxidized slowly to form Co(III)-nitrosyl. The capability of aquocobalamin to combine with NO had functional consequences. We found that nitrosylcobalamin had diminished ability to serve as a cofactor for the enzyme methionine synthase, and that aquocobalamin could quench NO-mediated inhibition of cell proliferation. Our in vitro studies therefore suggest that interactions between NO and cobalamins may have important consequences in vivo.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

September 1, 1996

Volume

88

Issue

5

Start / End Page

1857 / 1864

Location

United States

Related Subject Headings

  • Vitamin B 12
  • Spectrophotometry
  • Nitric Oxide
  • Immunology
  • Hydroxocobalamin
  • Humans
  • Hemoglobins
  • HL-60 Cells
  • Electron Spin Resonance Spectroscopy
  • Cobamides
 

Citation

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MLA
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Brouwer, M., Chamulitrat, W., Ferruzzi, G., Sauls, D. L., & Weinberg, J. B. (1996). Nitric oxide interactions with cobalamins: biochemical and functional consequences. Blood, 88(5), 1857–1864.
Brouwer, M., W. Chamulitrat, G. Ferruzzi, D. L. Sauls, and J. B. Weinberg. “Nitric oxide interactions with cobalamins: biochemical and functional consequences.Blood 88, no. 5 (September 1, 1996): 1857–64.
Brouwer M, Chamulitrat W, Ferruzzi G, Sauls DL, Weinberg JB. Nitric oxide interactions with cobalamins: biochemical and functional consequences. Blood. 1996 Sep 1;88(5):1857–64.
Brouwer, M., et al. “Nitric oxide interactions with cobalamins: biochemical and functional consequences.Blood, vol. 88, no. 5, Sept. 1996, pp. 1857–64.
Brouwer M, Chamulitrat W, Ferruzzi G, Sauls DL, Weinberg JB. Nitric oxide interactions with cobalamins: biochemical and functional consequences. Blood. 1996 Sep 1;88(5):1857–1864.

Published In

Blood

ISSN

0006-4971

Publication Date

September 1, 1996

Volume

88

Issue

5

Start / End Page

1857 / 1864

Location

United States

Related Subject Headings

  • Vitamin B 12
  • Spectrophotometry
  • Nitric Oxide
  • Immunology
  • Hydroxocobalamin
  • Humans
  • Hemoglobins
  • HL-60 Cells
  • Electron Spin Resonance Spectroscopy
  • Cobamides