Methemoglobin derivatives

Everse J. Photochemical reduction of methemoglobin and methemoglobin derivatives. Meth Enzymol 1994 231 524. 

As previously noted, many aromatic amines and their metabolites and derivatives are methemoglobin-generating chemicals (Smith 1996). 

This Fe(IV)-derivative is particularly stable with leghemoglobin, while with other hemoglobins and with myoglobins the oxy form is regenerated with H2O2 The reaction of sufficient concentrations of H Oj with methemoglobin could formally yield the OH radical ... 

Because the erythrocyte is a relatively simplified cell with a circumscribed function it would seem that superoxide dismutase must act to prevent a deleterious effect of O2 on the erythrocyte s capacity to transport oxygen. Superoxide might react with hemoglobin to form a derivative which cannot reversibly bind O . One such reaction is to mediate the formation of methemoglobin, the derivative of hemoglobin in which the Fe in heme is converted to Fe . The ability of O to react with hemoglobin to form methemoglobin has been proposed to occur 201,207-209) jjj... 

When the taurine chloramine uptake rate exceeds the rate of NADPH-dependent regeneration of GSH, there is a net loss of cellular GSH level, causing protein-thiol oxidation, ATP loss, and disruption of cellular metabolism. Heme moieties are the other target of chloramine attack on cellular constituents. Oxidation of hemoglobin to methemoglobin (and other hemoproteins to their oxidized derivatives) occurs at 10-fold excess of chloramine taurine molar concentration compared... 

Steinhaus, R.K., Baskin, S.I., Clark, J.H., Kirby, S.D. (1990). Formation of methemoglobin and metmyoglobin using 8-aminoquinoline derivatives or sodium nitrite and subsequent reaction with cyanide. J. Appl. Toxicol. 10 345-51. 

It is an in vitro mutagen in most test systems, at levels as small as 10-20 mmol 1 in some systems. Industrially used hydroxylamines were studied in human blood cells in vitro. The parent compound hydro-xylamine and the O-ethyl derivative gave very similar results. Both compounds induced a high degree of methemoglobin formation and glutathione depletion. Cytotoxicity was visible as Heinz body formation and hemolysis. 

A study of the toxicities of 21 aniline derivatives, using rats as test animals, showed that the three nitroanilines (2a, 2b and 2c) and 3,4-dichloroaniline (4) were equipotent to aniline, 3-chloroaniline (5a) and 4-chloroaniline (5b) were more potent than aniline, and the others were less potent or did not bring about changes in methemoglobin levels10. 

Ciccoli and coworkers have shown that incubation of rat erythrocytes with hydroxy lated metabolites of aniline, dapsone (39) and the corresponding hydroxylamines brings about enhanced release of iron and methemoglobin formation. This did not occur with parent compounds. That xenobiotics are effective only after biotransformation to metabolites in vivo is supported by acute intoxication of rats with aniline or 39 and marked increase in the erythrocyte content of free iron and of methemoglobin144. The potent toxicity of aniline-derived aminophenylnorharman in the liver of the gpt delta transgenic mouse has been demonstrated145,146. 

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. 

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