Catalytic selenols couple the redox cycles of metallothionein and glutathione.
Co-ordination of zinc to the thiol group of cysteine allows mobilization of zinc through oxidation of its ligand. This molecular property links the binding and release of zinc in metallothionein (MT) to the cellular redox state [Maret W. & Vallee B.L. (1998) Proc. Natl Acad. Sci. USA 95, 3483-3488]. Biological disulfides such as glutathione disulfide (GSSG) oxidize MT with concomitant release of zinc, while glutathione (GSH) reduces the oxidized protein to thionein, which then binds to available zinc. Neither of these two redox processes is very efficient, even at high concentrations of GSSG or GSH. However, the GSH/GSSG redox pair can efficiently couple with the MT/thionein system in the presence of a selenium compound that has the capacity to form a catalytic selenol(ate). This coupling provides a very effective means of modulating oxidation and reduction. Remarkably, selenium compounds catalyze the oxidation of MT even under overall reducing conditions such as those prevailing in the cytosol. In this manner, the binding and release of zinc from zinc-thiolate co-ordination sites is linked to redox catalysis by selenium compounds, changes in the glutathione redox state, and the availability of either a zinc donor or a zinc acceptor. The results also suggest that the pharmacological actions of selenium compounds in cancer prevention and other antiviral and anti-inflammatory therapeutic applications, as well as unknown functions of selenium-containing proteins, may relate to coupling between the thiol redox state and the zinc state.
Chen
Y
Y
Center for Biochemical and Biophysical Sciences and Medicine, Harvard Medical School, Boston, MA 02115, USA.
Maret
W
W
D002384:Catalysis; D003538:Cystamine / Q000031:analogs & derivatives / Q000737:chemistry* / Q000494:pharmacology; D005978:Glutathione / Q000737:chemistry*; D019803:Glutathione Disulfide / Q000737:chemistry; D007700:Kinetics; D008668:Metallothionein / Q000737:chemistry*; D008956:Models, Chemical; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010640:Phenothiazines / Q000737:chemistry; D013056:Spectrophotometry, Ultraviolet; D015032:Zinc / Q000737:chemistry
D016566:Organoselenium Compounds; D010640:Phenothiazines; C014807:selenocystamine; D008668:Metallothionein; D005978:Glutathione; D015032:Zinc; D003538:Cystamine; D019803:Glutathione Disulfide; C009469:thionine