Nitrosyl hemoglobins

Hydroxyurea reacts with oxy, deoxy and metHb in vitro to form iron nitrosyl hemoglobin (HbNO) and transfers NO to 2-6% of the iron heme groups [115]. Trapping studies using cyanide and carbon monoxide indicate that hydroxyurea oxidizes both oxy and deoxyHb to metHb and reduces metHb to deoxyHb specifically identifying the reaction of hydroxyurea and metHb as the critical reaction in the formation of HbNO from hydroxyurea [115]. Scheme 7.16 depicts the proposed mechanisms of N O and HbNO formation during the reaction of deoxy and metHb with hydroxyurea. Oxidation of hydroxyurea by metHb produces deoxyHb and the nitroxide radical (25,... 

Local administration of NO to the lungs has been shown to reverse pulmonary hypertension in animal models [103], importantly with no systemic side effects. This is likely to be as a result of surplus NO being removed as nitrosyl-hemoglobin [104]. Such advantages of gaseous NO were first reported in 1991 [105, 106]. In 1999 and 2001 NO gas was approved as a drug in the USA and European Union, for treating hypoxemic respiratory failure in infants [107]. 

The formation of nitrosyl hemoglobin (HbNO) by direct reaction with HA, or indirectly with hydroxyurea that produces HA, was also demonstrated concomitantly with the formation of methemoglobin . ... 

Borishenko GG, Osipov AN, Kazarinov KD, Vladimirov Y. Photochemical reactions of nitrosyl hemoglobin during exposure to low-power laser irradiation. Biochemistry (Moscow) 1997 62 661-6. 

Hydroxycarbamide (hydroxyurea) is used to treat a variety of cancers, myeloproliferative disorders, and sickle cell disease, and has been studied in patients with HIV infection (1). It inhibits ribonucleotide reductase and increases concentrations of iron nitrosyl hemoglobin, nitrite, and nitrate, suggesting in vivo metabolism of hydroxycarbamide to nitric oxide (2). 

Wajnberg E, Linhares MP, El-Jaick LJ, Bemski G. 1992. Nitrosyl hemoglobin EPR components at low temperatures. EurBiophysJ2 y.51-6. ... 

Yonetani T, Tsuneshige A, Zhou Y, Chen X. 1998. Electron paramagnetic resonance and oxygen binding studies of alpha-nitrosyl hemoglobin a novel oxygen carrier having NO-assisted allosteric functions. JBiol Chem 273(32) 20323-20333. 

Jaszewski AR, Farm YC, Chen YR, Sato K, Corbett J, Mason RP. 2003. EPR spectroscopy studies on the stmctural transition of nitrosyl hemoglobin in the arterial-venous cycle of DEANO-treated rats as it relates to the proposed nitrosyl hemoglo-hin/nitrosothiol hemoglobin exchange. Free Radio Biol Med 35(4) 444 51. 

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