Direct transfer of copper from metallothionein to superoxide dismutase: a possible mechanism for differential supply of Cu to SOD and ceruloplasmin in LEC rats.
Copper (Cu) and zinc (Zn)-binding superoxide dismutase (Cu,Zn-SOD) is synthesized always in a form of holo-protein in the liver of LEC rats, a genetically disordered mutant strain in Cu metabolism which accumulates Cu in a form bound to metallothionein (MT). On the other hand, ceruloplasmin (Cp) is synthesized in the liver and excreted into the blood plasma mostly as an apo-protein before the onset of acute hepatitis, and then holoform at the onset of jaundice. Thus, Cu is supplied differentially between Cp and SOD, and at different times, i.e., before and at the onset of acute hepatitis. Availability of Cu to apo-SOD was examined to explain the mechanisms for the differential supply of Cu among three different Cu forms; i) cuprous ion bound to glutathione, ii) free cupric ion, and iii) cuprous ion bound to MT. Cu was transferred to SOD from the three Cu complexes though MT-bound Cu was a less efficient Cu source to apo-SOD. The results indicate that SOD is always present in a holo-form in LEC rats because even MT-bound Cu can be supplied to SOD, while Cp is present in an apo-form because Cu is sequestered to MT and not available in free ionic forms in LEC rats before the onset of acute hepatitis.
Faculty of Pharmaceutical Sciences, Chiba University, Japan.
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KT
Suzuki
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Kuroda
D000818:Animals; D002570:Ceruloplasmin / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003300:Copper / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000096:biosynthesis / Q000378:metabolism*
D003300:Copper; D008668:Metallothionein; D013482:Superoxide Dismutase; D002570:Ceruloplasmin