HNO trapping and assisted decomposition of nitroxyl donors by ferric hemes

S. A. SUAREZ; M.A. MARTI; P. M. DE BIASE; D.A. ESTRIN; S. E. BARI; F. DOCTOROVICH

POLYHEDRON

Elsevier

Año: 2007 vol. 26 p. 4673 - 4679

0277-5387

    The role of nitric oxide (NO) as a signalling molecule in biological systems has been thoroughly studied in the last decades. Morerecently, there has been an increasing interest in the one-electron reduction product of NO, namely nitroxyl (HNO/NOÀ). Some studiessuggest that nitroxyl can be produced by nitric oxide synthases under certain conditions, and that distinct pharmacological effects areobserved for NO and nitroxyl donors. HNO is capable of react with heme proteins, thiols, molecular oxygen, NO and HNO itself. How-ever, only recently the different reactivity patterns are being thoroughly understood. Heme model compounds offer the opportunity tostudy the reaction kinetics without the complexity arising from ligand interactions with the protein matrix. In this study we analyzed thereaction between the commonly used nitroxyl donors sodium trioxodinitrate and toluene sulfohydroxamic acid, with the ferric modelcompounds microperoxidase-11 (MP11) and the cationic metalloporphyrin [FeIIITEPyP]5+ (Tetrakis N-ethylpyridinium-2yl porphyne).Our results show that there are two alternative modes of reactivity for nitroxyl donors towards heme in aqueous solutions. The first onecomprises the heme assisted decomposition of the donor, enhancing its decomposition rate more than 100-fold. In the second, the donorproduces HNO which subsequently reacts with the porphyrin. The observed rate constants (of about 105 MÀ1 sÀ1) are consistent with theestimated data for the HNO reaction with heme proteins, and may be controlled by the leaving water ligand. This rate constant probablyrepresents an upper limit for the bimolecular rate constant of HNO towards these proteins.