The Copper(II)‐Catalyzed Oxidation of Glutathione

Abstract

The kinetics and mechanisms of the copper(II)-catalyzed GSH (glutathione) oxidation are examined in the light of its biological importance and in the use of blood and/or saliva samples for GSH monitoring. The rates of the free thiol consumption were measured spectrophotometrically by reaction with DTNB (5,5'-dithiobis-(2-nitrobenzoic acid)), showing that GSH is not auto-oxidized by oxygen in the absence of a catalyst. In the presence of Cu , reactions with two timescales were observed. The first step (short timescale) involves the fast formation of a copper-glutathione complex by the cysteine thiol. The second step (longer timescale) is the overall oxidation of GSH to GSSG (glutathione disulfide) catalyzed by copper(II). When the initial concentrations of GSH are at least threefold in excess of Cu , the rate law is deduced to be -d[thiol]/dt=k[copper-glutathione complex][O ] [H O ] . The 0.5 reaction order with respect to O reveals a pre-equilibrium prior to the rate-determining step of the GSSG formation. In contrast to [Cu ] and [O ], the rate of the reactions decreases with increasing concentrations of GSH. This inverse relationship is proposed to be a result of the competing formation of an inactive form of the copper-glutathione complex (binding to glutamic and/or glycine moieties).

Mesoporous Rod‐Like Metal‐Organic Framework with Optimal Tumor Targeting Properties for Enhanced Activatable Photodynamic Therapy

“…It indicates that they inherit the potent GSH scavenging capability from copper(II). [ 27 ] Therefore, both nanoscale mesoporous rod‐like and cube‐like Cu‐MOFs are successfully synthesized and found to be promising GSH‐responsive and GSH‐depletion drug carriers.…”

Staphylococcus aureus lacking a functional MntABC manganese import system has increased resistance to copper

“…Under Mn deplete conditions, mntABC is expressed and Cu(II) enters S. aureus cells by a MntABC-dependent mechanism. Once inside, cellular reductants reduce Cu(II) to Cu(I) (Ngamchuea et al, 2016;Rigo et al, 2004;Scarpa et al, 1996). The Cu(I) can associate with the CsoR transcriptional repressor resulting in derepression of the copAZ and copBL operons (Grossoehme et al, 2011;Rosario-Cruz et al, 2019).…”

Rapid Method for the Quantification of Reduced and Oxidized Glutathione in Human Plasma and Saliva

“…At this high concentration of EDTA, it has been reported that oxidation of GSH to GSSG in nonbiological media does not occur within 3 hours with the experimental errors of less than ±2%. 30 The reference GSH:GSSG ratio in the solution can therefore be taken from the concentrations of GSH and GSSG used to prepare the solution. The ratios of GSH:GSSG measured using the assay are 98.7 ± 1.3 % of the actual ratios of GSH:GSSG in the solutions, as displayed as a scattered plot in Figure 1c, evidencing the high accuracy of the developed assay.…”