Reactions of HNO with Heme Proteins: New Routes to HNO−Heme Complexes and Insight into Physiological Effects

Abstract

The formation and interconversion of nitrogen oxides has been of interest in numerous contexts for decades. Early studies focused on gas-phase reactions, particularly with regard to industrial and atmospheric environments, and on nitrogen fixation. Additionally, investigation of the coordination chemistry of nitric oxide (NO) with hemoglobin dates back nearly a century. With the discovery in the early 1980s that NO is biosynthesized as a molecular signaling agent, the literature has been focused on the biological effects of nitrogen oxides, but the original concerns remain relevant. For instance, hemoglobin has long been known to react with nitrite, but this reductase activity has recently been considered to be important to produce NO under hypoxic conditions. The association of nitrosyl hydride (HNO; also commonly referred to as nitroxyl) with heme proteins can also produce NO by reductive nitrosylation. Furthermore, HNO is considered to be an intermediate in bacterial denitrification, but conclusive identification has been elusive. The authors of this article have approached the bioinorganic chemistry of HNO from different perspectives, which have converged because heme proteins are important biological targets of HNO.

Nitrosomonas europaea cytochrome P460 is a direct link between nitrification and nitrous oxide emission

“…The EPR spectrum of this sample shows signals for Fe III -NH 2 OH and {FeNO} 7 (Fig. 4D) (35,36) and Fe II -HNO, which has been characterized in only one biological system, the myoglobin-HNO complex (37,38). Finally, because N 2 O is the product of NH 2 OH oxidation by cyt P460 under our experimental conditions, an Fe-N 2 O complex is also possible.…”

Three Redox States of Metallonitrosyls in Aqueous Solution

“…The reduction led to nearly quantitative formation of the product as revealed spectrophotometrically. Using BH 4 À as an alternative reductant has been recommended as a better choice for preparing [Fe II (CN) 5 HNO] 3À , though only $20% yields could be reached (169). The main absorption band of , >80%), with a half-life time of $50 min.…”

“…This seems inconsistent, given that the 445-nm band (MLCT in origin) should expectedly shift upon deprotonation of HNO. Besides, the properties of the stable iron hemenitroxyl derivative Hb II HNO (Table 3) were reported to remain unchanged in aqueous solution up to pH $10-11 (17,169).…”

HBOC Vasoactivity: Interplay Between Nitric Oxide Scavenging and Capacity to Generate Bioactive Nitric Oxide Species

“…Exogenous acellular oxy-or deoxy-Hb results in vasoconstriction and transient hypertension (15,111,130). In the presence of acellular Hb, NO is predominantly quenched through an NO dioxygenation (NOD) reaction and to a lesser degree through the formation of the ''dead end'' (highly stable and relatively nonreactive) ferrous heme-nitrosyl form, either through the rapid binding of NO to five coordinate ferrous hemes (as in deoxy Hb) or through reductive nitrosylation subsequent to the binding of NO to ferric (as in metHb) heme centers (77,111,120,157). The NOD reaction involves the efficient reaction of NO with oxy-hemes to form met (ferric) heme and nitrate.…”