Hemoglobin methylation

Hematological Effects. No information was found regarding hematological effects in humans following exposure to methyl parathion. Repeated oral exposure to methyl parathion resulted in decreased mean corpuseular volume in one study and decreased hematocrit and erythrocyte count in another study in rats. Chronic ingestion of methyl parathion induced reduction of mean hemoglobin, hematocrit, and erythrocyte eounts in rats. 

Hemoglobin is another heme-containing protein, which has been shown to be active towards PAH, oxidation in presence of peroxide [420], This protein was also modified via PEG and methyl esterification to obtain a more hydrophobic protein with altered activity and substrate specificity. The modified protein had four times the catalytic efficiency than that of the unmodified protein for pyrene oxidation. Several PAHs were also oxidized including acenaphthene, anthracene, azulene, benzo(a)pyrene, fluoranthene, fluorene, and phenanthrene however, no reaction was observed with chrysene and biphenyl. Modification of hemoglobin with p-nitrophenol and p-aminophenol has also been reported [425], The modification was reported to enhance the substrate affinity up to 30 times. Additionally, the solvent concentration at which the enzyme showed maximum activity was also higher. Both the effects were attributed to the increase in hydrophobicity of the active site. 

Experiments using synthetic hydroxyurea derivatives provide information regarding the mechanism and the structural features required for NO release. O-Methyl-hydroxyurea (27, Fig. 7.5) fails to react with any type of hemoglobin [115]. N-... 

Methylhydroxyurea (28, Fig. 7.5) oxidizes oxyHb to metHb and reduces metHb to deoxyHb but neither of these reactions produces HbNO, further supporting the mechanism depicted in Scheme 7.16 for the formation of NO and HbNO from the reactions of hydroxyurea and hemoglobin [115]. The O-methyl group of 27 prevents the association and further reaction of 27 with the heme iron [115]. Scheme 7.16 predicts the redox chemistry observed during the reaction of 28 with hemoglobin and the failure to detect HbNO shows the inability of 28 or any derivative radicals to transfer NO during these reactions [115]. These results indicate that nitric oxide transfer in these reactions of hydroxyurea requires an unsubstituted acylhydroxylamine (-NHOH) group. 

Methyl iodide is considered a potent methylating agent it methylates hemoglobin in experimental animals and humans. In DNA binding studies in rats, adducts were found in all organs examined, with the highest levels in the stomach and forestomach, after both oral and inhalation administration. It is mutagenic... 

Tsuchida et al. [33], synthesized Poly(l-vinyl and l-vinyl-2-methyl-imidazole) bound heme (iron-porphyrin) complexes as models for mimicking natural oxygen carriers such as hemoglobin. The reaction between AIBN polymerized poly(l-vinyl)imidazole, or poly(l-vinyl-2-methylimidazole) and Fe(III) protoporphyrin IX diethyl ester in DMF and small amount of Na2S204 yields the Fe(III) complex (Fig. 15),... 

Iwasaki, K. (1988a) Determination of. S -methylcysteine in mouse hemoglobin following exposure to methyl bromide. Ind. Health, 26, 187-190... 

Iwasaki, K., Ito, I. Kagawa, J. (1989) Biological exposure monitoring of methyl bromide workers by determination of hemoglobin adducts. Ind. Health, 27, 181-183... 

Iron protoporphyrin IX (heme) is found in the b-type cytochromes and in hemoglobin and myoglobin. In heme c, cysteine residues of the protein (R) are attached covalently by thioether links to the two vinyl (—CH=CH2) groups of protoporphyrin IX. Heme c is found in the c cytochromes. In heme A, which is found in the a cytochromes, a 15-carbon isoprenoid side chain is attached to one of the vinyls, and a formyl group replaces one of the methyls. 

Blood proteins, such as hemoglobin, may be used in tests of human exposure because blood is readily and safely accessible. For example, the exposure of mice to ethylene oxide or dimethylnitrosamine was estimated by measuring alkylated residues in hemoglobin. The method was subsequently extended to people exposed occupationally to ethylene oxide by measuring 7V-3-(2-hydroxycthyl) histidine residues in hemoglobin. Similarly methyl cysteine residues in hemoglobin can be used as a measure of methylation. 

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