Copper-glutathione complexes under physiological conditions: structures in solution different from the solid state coordination

Abstract

The physiologically important copper complexes of oxidized glutathione have been examined by electron spin resonance (ESR) spectroscopy in aqueous solution at neutral pH. Low temperature measurements show that the Cu(ll) binding site in oxidized glutathione has the same ligand arrangement as in the copper complexes of S-methylglutathione, glutamine, glutamate and glycine. The site is composed of the amino nitrogens and the carboxyl oxygens of two ?-glutamyl residues; there is no interaction with amide nitrogens, the sulphur bond or the glycyl carboxyl groups. At high metal to ligand ratios a binuclear species exists, in which each Cu(II) binds only to one 7-glutamyl residue. The previously reported forbidden transition detected at g = 4 is due to non-specific aggregation and not to spin coupling of intramolecular sites. Liquid solution ESR spectra show the Cu(II)-glutathione complex has a lower mobility than the corresponding Cu(II)-S-methylglutathione species. From the degree of spectral anisotropy the complex with glutathione is calculated to exist as a dimer. These results demonstrate that the physiologically relevant complex between copper and oxidized glutathione in solution is completely different from the known solid state structure determined by crystallography.

Mechanisms underlying the inhibition of the cytochrome P450 system by copper ions

“…Recently, it has been reported that copper ions and GSH interact swiftly to form the complex Cu + -GSH, conjugate that would also generate superoxide radicals (Speisky et al, 2008). Although the speciation of copper ions participating in the GSH complex is a matter of controversy, there are several reports showing the physiological role of Cu + -GSH complexes in copper transport (Suzuki et al, 1989;Mehra and Mulchandani, 1995;Musci et al, 1996;Pederson et al, 1996). Since no reducing agent with enough reducing potential for the reduction of Cu 2+ to Cu + is present in our experiments of Cu 2+ binding to GSH, our data suggest that the complex Cu 2+ -GSH can also occur in vitro.…”

Application of ergothioneine-rich extract from an edible mushroom Flammulina velutipes for melanosis prevention in shrimp, Penaeus monodon and Litopenaeus vannamei

“…A study conducted by Ey, Schömig, and Taubert (2007) reported that the efficacy of ESH in diminishing Cu 2 + -induced toxicity is probably due to the formation of a 2:1 chelate complex that could be isolated from OCTN 1-transfected KEK-293 cells after treatment with ESH and Cu 2+ . In addition, the formation of a stable ESH-Cu 2+ complex by applying a chemical titration technique has been proposed in an earlier study (Pedersen, Steinkuhler, Wesser, & Rotilio, 1996).…”

Redox-implications associated with the formation of complexes between copper ions and reduced or oxidized glutathione

“…The studies on the complexes formed between GSSG and copper have been largely limited to the use of cupric ions. As early shown by several laboratories [96][97][98], the addition of GSSG to a solution containing Cu 2+ ions leads to the swift formation of stable Cu(II)-oxidized glutathione complexes suitable for spectroscopic analysis. Kroneck [99] was first in proposing a model for the structure of these complexes, suggesting that, at alkaline pH, a binuclear complex is formed in which each Cu(II) is bonded to five donor atoms from one GS − moiety (two deprotonated amide nitrogen, the glutamyl carboxyl oxygen, an amine nitrogen, and the glycyl carboxyl oxygen).…”