Generation of carbon monoxide and iron from hemeproteins in the presence of 7,8-dihydroneopterin.
7,8-Dihydroneopterin and neopterin are secreted by human and primate macrophages after activation by interferon-gamma 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.
Horejsi
Renate
R
Institute for Medical Chemistry and Pregl Laboratory, University Graz, Harrachgasse 21/II, Austria. renate.horejsi@kfunigraz.ac.at
Jung
Christiane
C
Möller
Reinhard
R
Tafeit
Erwin
E
Reibnegger
Gilbert
G
D000818:Animals; D002248:Carbon Monoxide / Q000737:chemistry*; D005296:Ferrous Compounds / Q000737:chemistry; D006420:Hemeproteins / Q000737:chemistry*; D006736:Horses; D006801:Humans; D007501:Iron / Q000737:chemistry*; D007700:Kinetics; D019798:Neopterin / Q000031:analogs & derivatives; D011621:Pteridines / Q000737:chemistry*; D013057:Spectrum Analysis
D005296:Ferrous Compounds; D006420:Hemeproteins; D011621:Pteridines; C000976:7,8-dihydroneopterin; C020748:ferrous sulfate; D019798:Neopterin; D002248:Carbon Monoxide; D007501:Iron