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J Biol Chem, Vol. 275, Issue 3, 1551-1556, January 21, 2000

Nitric Oxide-forming Reaction between the Iron-N-Methyl-D-glucamine Dithiocarbamate Complex and Nitrite*

Koichiro TsuchiyaDagger , Masanori Yoshizumi§, Hitoshi Houchi, and Ronald P. Mason

From the Free Radical Metabolite Section, Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, Research Triangle Park, North Carolina 27709, the § Department of Pharmacology and the  Department of Pharmacy, School of Medicine, The University of Tokushima, Kuramoto, Tokushima 770, Japan

The objective of this study was to elucidate the origin of the nitric oxide-forming reactions from nitrite in the presence of the iron-N-methyl-D-glucamine dithiocarbamate complex ((MGD)2Fe2+). The (MGD)2Fe2+ complex is commonly used in electron paramagnetic resonance (EPR) spectroscopic detection of NO both in vivo and in vitro. Although it is widely believed that only NO can react with (MGD)2Fe2+ complex to form the (MGD)2Fe2+·NO complex, a recent article reported that the (MGD)2Fe2+ complex can react not only with NO, but also with nitrite to produce the characteristic triplet EPR signal of (MGD)2Fe2+·NO (Hiramoto, K., Tomiyama, S., and Kikugawa, K. (1997) Free Radical Res. 27, 505-509). However, no detailed reaction mechanisms were given. Alternatively, nitrite is considered to be a spontaneous NO donor, especially at acidic pH values (Samouilov, A., Kuppusamy, P., and Zweier, J. L. (1998) Arch Biochem. Biophys. 357, 1-7). However, its production of nitric oxide at physiological pH is unclear. In this report, we demonstrate that the (MGD)2Fe2+ complex and nitrite reacted to form NO as follows: 1) (MGD)2Fe2·NO complex was produced at pH 7.4; 2) concomitantly, the (MGD)3Fe3+ complex, which is the oxidized form of (MGD)2Fe2+, was formed; 3) the rate of formation of the (MGD)2Fe2+·NO complex was a function of the concentration of [Fe2+]2, [MGD], [H+] and [nitrite].


* The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Dagger To whom correspondence should be addressed: Laboratory of Pharmacology and Chemistry, NIEHS, National Institutes of Health, F0-02, Research Triangle Park, NC 27709. Tel.: 1-919-541-7573; E-mail: tsuchiya@niehs.nih.gov.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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