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Generation of carbon monoxide and iron from hemeproteins in the presence of 7,8-dihydroneopterin

Item Type:Article
Title:Generation of carbon monoxide and iron from hemeproteins in the presence of 7,8-dihydroneopterin
Creators Name:Horejsi, R. and Jung, C. and Moeller, R. and Tafeit, E. and Reibnegger, G.
Abstract:7,8-Dihydroneopterin and neopterin are secreted by human and primate macrophages after activation by interferon-γ in a ratio of 2:1. 7,8-Dihydroneopterin is known to suppress radical-mediated processes, but it is also able in the presence of iron ions to generate superoxide radical anion and hydroxyl radicals from molecular oxygen. Effects of 7,8-dihydroneopterin were investigated on (met)myoglobin and (met)hemoglobin. Addition of 7,8-dihydroneopterin to heme proteins in air-saturated solution resulted in dose-dependent cleavage of the porphyrin moiety. The liberation of non-heme iron and carbon monoxide originating from the cleaved porphyrin was quantified. Both were generated at equimolar concentrations with a linear correlation coefficient of 0.9. Addition of ferrous iron significantly accelerated the pteridine-mediated cleaving of the porphyrin. However, the total yield of porphyrin cleaved was controlled by the pterin rather than by the ferrous ion concentration. 7,8-Dihydroneopterin is assumed to reduce the heme iron in intact protein molecules, thereby preparing the conditions for binding of oxygen and carbon monoxide as ligands. Beyond that, it is concluded that hydroxyl radicals might be generated via reduction of molecular oxygen to superoxide anion in the autoxidation process and dismutation to hydrogen peroxide and subsequent Fenton reaction.
Keywords:7,8-Dihydroneopterin, Hemoglobin, Myoglobin, Porphyrin Cleavage, Animals, Horses
Source:Biochimica et Biophysica Acta - General Subjects
ISSN:0006-3002
Publisher:Elsevier (The Netherlands)
Volume:1571
Number:2
Page Range:124-130
Date:6 June 2002
Official Publication:https://doi.org/10.1016/S0304-4165(02)00206-4
PubMed:View item in PubMed

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