Methemoglobin hydroxyl

Aromatic amines are initially metabolized by aromatic and A -hydroxylation (oxidation reactions) and Y-acetylation. Following aromatic ring hydroxylation, the ring structure may be further conjugated with glucuronic acid or sulfate (Parkinson 1996). N-hydroxylation results in the potential methemoglobin-generating metabolite,... 

In the presence of oxygen, dissolved hemoglobin is slowly oxidized to methemoglobin, a derivative of hemoglobin in which the iron is present in the ferric (Fe +) state. In metHb, the ferric ion is bound tightly to a hydroxyl group or to some other anion. The heme porphyrin (protoporphyrin IX) that contains an Fe + ion is known as hemin. 

Above pH 8.8, where further decrease of hydrogen ion concentration leads to increased formation of alkaline peroxidase, peroxide complex formation is suppressed, which indicates that peroxides cannot replace the covalently bound hydroxyl group. There is an interesting parallel here in the case of methemoglobin where Haurowitz claimed that the alkaline form cannot give a peroxide complex (44). 

Cimetidine increases plasma dapsone concentrations without increased hemolysis, reduces methemoglobin concentrations by selective inhibition of dapsone N-hydroxyl-ation, and does not interfere with the control of the skin disorder. These features seem to be detectable within weeks and are sustained. The effects of cimetidine appear to be greatest on methemoglobin concentrations. 

Other substances that have been tested in the lab on animals include stroma-free methemoglobin solutions, alpha-ketoglutaric acid, chlorpromazine, hydroxyl-amine, phenoxybenzamine, centrophenoxine, naloxone, etomidate, para-aminopropiophenone, and calcium channel blockers (Ashton et al., 1980 Dubinsky et al., 1984 Leung et al., 1984 Ten Eyck et al., 1985 Johnson et al., 1986 Bright and Marts, 1987 Yamamoto, 1990 Budavari, 2000). The use of these substances has shown positive results, but they have not been tried during actual poisoning situations. 

The theoretical estimation of the equilibrium reaction of Hb with potassium cyanide over a wide range of pH was first studied. In aqueous solutions with different pH values, Hb coexists in two different forms Hb OH2 (acidic methemoglobin) in which the water molecule is attached to the 6th coordination site of ferri-protoporphyrin IX, and HbOH (alkaline methemoglobin) in which the H2O of Hb OH2 is replaced by a hydroxyl ion. The equilibrium reaction between both types is represented by [20] ... 

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