Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Metallothioneins isolated from the hepatopancreas of the edible crab (Cancer paqurus) and the plaice (Pleuronectes platessa) after cadmium injection are predominantly cadmium proteins containing only small amounts of zinc and traces of copper. The removal of metal ions from the two metallothioneins by EDTA was studied using proton NMR spectroscopy. The rates of removal of cadmium and zinc were monitored directly from the intensity of the resonances due to the cadmium and zinc-EDTA complexes. Nearly all the zinc present in the protein was extracted by EDTA relatively rapidly, whereas only 10 to 20% of the total cadmium was removed in at least three steps. The total (Cd + Zn) metal removed at equilibrium was 1.2 to 1.8 g-ions/mole protein. Information on conformational changes in the protein were also obtained from studying alterations in the proton resonances of the protein. This was directly correlated with removal of metal from the protein. The coordination environments of the cadmium ions in crab metallothionein were investigated by using 113Cd-NMR, and compared with 113Cd-NMR spectra of rabbit liver MT-II and Scylla serrata MT-I.
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PMID:NMR studies of crab and plaice metallothioneins. 308 76

Wilson's disease is a rare inherited disorder of copper (Cu) metabolism characterized by the deposition of Cu in the liver, brain, and cornea. The levels of metallothionein (MT), Cu, and zinc (Zn) in the livers of two Wilson's disease patients were analyzed in this study. About 50-fold increase in the Cu levels above normal controls was observed in both patients (160 and 298 micrograms/g of wet tissue). About 73% of subcellular Cu was present in the cytoplasmic fraction and most of it was in association with MT. Analysis of hepatic MT levels showed a 3-fold increase (863 micrograms/g of wet tissue) over control human levels (321 micrograms/g of wet tissue). The two forms of MT (MT-I and MT-II) were isolated from one liver sample. Both forms contained high amounts of Cu (11 to 12 g atoms/mole), indicating saturation of MT which had only 2 to 3 g atoms of zinc. The distribution of MT in the hepatocytes was investigated using an immunohistochemical method. In tissue sections with minimal tissue damage, there was intense cytoplasmic staining for MT in hepatocytes whereas both nuclear and cytoplasmic staining was found in tissue sections with extensive necrosis and fibrosis. These results suggest that MT is the major hepatic Cu-binding protein in Wilson's disease, that it is present in a form saturated with Cu, and that only in degenerating hepatocytes is it found in the nucleus as well as the cytoplasm.
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PMID:Hepatic copper and metallothionein distribution in Wilson's disease (hepatolenticular degeneration). 331 8

Because metallothionein (MT) may undergo thiol-disulfide or other redox reactions under certain cellular conditions, the partially and completely oxidized products of the reactions of Cd7-MT-II with the electrophile 5,5'-dithiobis(2-nitrobenzoic acid), ESSE, and oxidized glutathione, GSSG, were characterized. Reaction with the stoichiometric quantity of ESSE (1 ESSE per MT thiolate) generates monomeric and polymeric MTs with three types of disulfide bonds: intra- and intermolecular CyS-SCy linkages and a small number (2-3/MT) of mixed disulfides, CyS-SE, involving thionitrobenzoate (ES-). Reaction with substoichiometric quantities of ESSE (0.02 or 0.1 per MT thiolate) causes the formation of intra- and intermolecular CyS-SCy disulfides, but no mixed disulfides. In the latter reactions, two equivalents of ES- are released per mole of ESSE, but the release is described by a single first-order rate constant (k = 3.0 +/- 0.5 sec-1). Substantial amounts of cadmium remained bound to the MT monomers and polymers after reaction with the substoichiometric quantities. Despite the Cd bound to the MT after reaction with 0.1 ESSE per MT thiolate, no 111Cd NMR signals were detected, indicating rapid equilibration of the remaining metal ions among the disrupted binding sites. Large excesses of the endogenous aliphatic disulfide, GSSG, displace Zn+2 from Zn7-MT slowly. The reaction is complete after 24 hours with 5000 microM GSSG, but only 25% complete after 72 hours with 250 microM GSSG. Approximately one Cd+2 is displaced rapidly from Cd7MT by 5000 microM GSSG and half as much by 250 microM GSSG, but no further reaction occurs. It is unlikely that GSSG oxidation of MTs would be physiologically significant.
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PMID:The oxidation of rabbit liver metallothionein-II by 5,5'-dithiobis(2-nitrobenzoic acid) and glutathione disulfide. 812 May 30