Fast Nitroxyl Trapping by Ferric Porphyrins

S. E. BARI; M. MARTI; V. AMOREBIETA; D. A. ESTRIN; F. A. DOCTOROVICH

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

ACS

Año: 2003 vol. 125 p. 15272 - 15273

0002-7863

Nitroxyl anion (NO-), the elusive one- electron reduction product of nitric oxide (NO), is currently being considered as a product of the enzyme nitric oxide synthase (NOS).1 It is also biosynthesized from N-hydroxy-L-arginine under oxidative stress2 or nonenzymatically from the reaction of S-nitrosothiols with thiols.3 Nevertheless, it has been recently demonstrated that the direct one-electron reduction of NO is thermodynamically unfavored under physiological conditions,4 where the conjugated weak acid nitroxyl (HNO) is the predominant species.5 The anion or its conjugated acid are capable of reacting with heme or non-heme iron6 and with thiol residues, respectively, pointing to hemeproteins as relevant biochemical targets.7 However, no studies have been reported on the reactions of heme model systems with NO-/HNO. In this work we report for the first time an investigation of the reactions of NO-/ HNO with ferriheme model systems. These reactions not only shed light on the putative mechanisms operating under physiological conditions but could also provide a powerful tool for the discrimination of NO and NO-/HNO biological effects by selective trapping.-), the elusive one- electron reduction product of nitric oxide (NO), is currently being considered as a product of the enzyme nitric oxide synthase (NOS).1 It is also biosynthesized from N-hydroxy-L-arginine under oxidative stress2 or nonenzymatically from the reaction of S-nitrosothiols with thiols.3 Nevertheless, it has been recently demonstrated that the direct one-electron reduction of NO is thermodynamically unfavored under physiological conditions,4 where the conjugated weak acid nitroxyl (HNO) is the predominant species.5 The anion or its conjugated acid are capable of reacting with heme or non-heme iron6 and with thiol residues, respectively, pointing to hemeproteins as relevant biochemical targets.7 However, no studies have been reported on the reactions of heme model systems with NO-/HNO. In this work we report for the first time an investigation of the reactions of NO-/ HNO with ferriheme model systems. These reactions not only shed light on the putative mechanisms operating under physiological conditions but could also provide a powerful tool for the discrimination of NO and NO-/HNO biological effects by selective trapping.