In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 95, No. 7 ( 1998-03-31), p. 3489-3494
Abstract:
Metallothionein (MT), despite its high metal binding
constant ( K Zn = 3.2 × 10 13 M −1 at pH 7.4), can transfer zinc to the apoforms of zinc
enzymes that have inherently lower stability constants. To gain insight into this paradox, we have studied zinc transfer between zinc enzymes and MT. Zinc can be transferred in both directions—i.e., from the
enzymes to thionein (the apoform of MT) and from MT to the apoenzymes. Agents that mediate or enhance zinc transfer have been identified that
provide kinetic pathways in either direction. MT does not transfer all of its seven zinc atoms to an apoenzyme, but apparently contains at
least one that is more prone to transfer than the others. Modification of thiol ligands in MT zinc clusters increases the total number of zinc
ions released and, hence, the extent of transfer. Aside from disulfide reagents, we show that selenium compounds are potential cellular
enhancers of zinc transfer from MT to apoenzymes. Zinc transfer from zinc enzymes to thionein, on the other hand, is mediated by
zinc-chelating agents such as Tris buffer, citrate, or glutathione. Redox agents are asymmetrically involved in both directions of zinc
transfer. For example, reduced glutathione mediates zinc transfer from enzymes to thionein, whereas glutathione disulfide oxidizes MT with
enhanced release of zinc and transfer of zinc to apoenzymes. Therefore, the cellular redox state as well as the concentration of other
biological chelating agents might well determine the direction of zinc transfer and ultimately affect zinc distribution.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.95.7.3489
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1998
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12