title: 1H-NMR study of the removal of methylmercury from intact erythrocytes by sulfhydryl compounds.
abstract: The effectiveness of penicillamine, N-acetylpenicillamine, meso-2,3-dimercaptosuccinic acid, 2,3-dimercaptopropanesulfonic acid, and dithioerythritol for removing methylmercury (CH3Hg(II) from intact human erythrocytes has been studied by 1H-nuclear magnetic resonance spectroscopy. The removal of CH3Hg(II) was monitored by measuring the chemical shift of the resonance for the proton on the alpha-carbon of the cysteinyl residue of intracellular glutathione in 1H-NMR spectra of intact, CH3Hg(II)-containing erythrocytes in suspensions to which the sulfhydryl ligands were added. Because exchange of intracellular glutathione between its free and CH3Hg(II) complexed forms is fast, the chemical shift of the cysteinyl resonance provides a direct, noninvasive measure of the fraction of intracellular glutathione that is complexed. The sulfhydryl ligands were found to remove CH3Hg(II) from intact erythrocytes in the order 2,3-dimercaptosuccinic acid greater than 2,3-dimercaptopropane sulfonic acid greater than dithioerythritol greater than penicillamine approximately N-acetylpenicillamine, which also is the order of the conditional formation constants of the CH3Hg(II) complexes at pH 7.4. All five ligands removed CH3Hg(II) from intact erythrocytes much more rapidly than can be accounted for by a mechanism in which the ligand crosses the membrane, combines with the CH3Hg(II), and then transports it out of the cell. An alternative mechanism is proposed in which the ligand reacts with CH3Hg(II) which is complexed by sulfhydryl groups of the membrane, which in turn react with the intracellular CH3Hg(II) to bring more CH3Hg(II) into the membrane, where it can react with the added sulfhydryl ligand.
mesh_terms: D004912:Erythrocytes / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008767:Methylmercury Compounds / Q000097:blood*; D013329:Structure-Activity Relationship; D013438:Sulfhydryl Compounds / Q000097:blood* / Q000494:pharmacology
chemical_list: D008767:Methylmercury Compounds; D013438:Sulfhydryl Compounds; C030957:methylmercury II