title: Oxidation of tetrahydrobiopterin by peroxynitrite or oxoferryl species occurs by a radical pathway.
abstract: The molecular mechanisms of tetrahydrobiopterin (BH4) oxidation by peroxynitrite (ONOO-) was studied using ultra-weak chemiluminescence, electron paramagnetic resonance (EPR) and UV-visible diode-array spectrophotometry, and compared to BH4 oxidation by oxoferryl species produced by the myoglobin/hydrogen peroxide (Mb/H2O2) system. The oxidation of BH4 by ONOO- produced a weak chemiluminescence, which was altered by addition of 50 mM of the spin trap alpha-(4-pyridyl-1-oxide)-N-tert butylnitrone (POBN). EPR spin trapping demonstrated that the reaction occurred at least in part by a radical pathway. A mixture of two spectra composed by an intense six-line spectrum and a fleeting weak nine-line one was observed when using ONOO-. Mb/H2O2 produced a short-living light emission that was suppressed by the addition of BH4. Simultaneous addition of POBN, BH4 and Mb/H2O2 produced the same six-line EPR spectrum, with a signal intensity depending on BH4 concentration. Spectrophotometric studies confirmed the rapid disappearance of the characteristic peak of ONOO- (302 nm) as well as substantial modifications of the initial BH4 spectrum with both oxidant systems. These data demonstrated that BH4 oxidation, either by ONOO- or by Mb/H2O2, occurred with the production of activated species and by radical pathways.
authors.affiliation: Laboratory of Homogeneous Catalysis-CERM, University of Liège, Institut de Chimie, Sart Tilman, Belgium. s.kohnen@ulg.ac.be
authors.forename: S L
authors.initials: SL
authors.lastname: Kohnen
authors.forename: A A
authors.initials: AA
authors.lastname: Mouithys-Mickalad
authors.forename: G P
authors.initials: GP
authors.lastname: Deby-Dupont
authors.forename: C M
authors.initials: CM
authors.lastname: Deby
authors.forename: M L
authors.initials: ML
authors.lastname: Lamy
authors.forename: A F
authors.initials: AF
authors.lastname: Noels
mesh_terms: D001708:Biopterins / Q000031:analogs & derivatives* / Q000378:metabolism*; D002713:Chlorine / Q000378:metabolism*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals / Q000378:metabolism*; D010084:Oxidation-Reduction; D010087:Oxides / Q000378:metabolism*; D030421:Peroxynitrous Acid / Q000378:metabolism*; D015398:Signal Transduction; D013056:Spectrophotometry, Ultraviolet; D013997:Time Factors
chemical_list: D005609:Free Radicals; D010087:Oxides; D030421:Peroxynitrous Acid; D001708:Biopterins; D002713:Chlorine; C041955:tetrachlorodecaoxide; C003402:sapropterin