The Formation Constants of Mercury(II)−Glutathione Complexes

Oram, Paul; Fang, Xiaojun; Fernaǹdo, Quintus; Letkeman, Peter; Letkeman, Douglas

doi:10.1021/tx9501896

Cited by 94 publications

(61 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The complex binding constants rely heavily on the pH and the buffer composition. Robust numbers are 10 42 for the Hg 2ϩ -bis-glutathionato complex (54) and 10 39 for the Cu ϩ -monoglutathionato complex (55), which easily explains the sensitivity of the copper resistance regulator CueR to zeptomolar levels of copper (6). The values for other transition metals should be below the copper and mercury values due to the lower affinity of these metals for sulfur.…”

Section: Discussionmentioning

confidence: 99%

Glutathione and Transition-Metal Homeostasis inEscherichia coli

et al. 2008

View full text Add to dashboard Cite

Glutathione (GSH) and its derivative phytochelatin are important binding factors in transition-metal homeostasis in many eukaryotes. Here, we demonstrate that GSH is also involved in chromate, Zn(II), Cd(II), and Cu(II) homeostasis and resistance in Escherichia coli. While the loss of the ability to synthesize GSH influenced metal tolerance in wild-type cells only slightly, GSH was important for residual metal resistance in cells without metal efflux systems. In mutant cells without the P-type ATPase ZntA, the additional deletion of the GSH biosynthesis system led to a strong decrease in resistance to Cd(II) and Zn(II). Likewise, in mutant cells without the P-type ATPase CopA, the removal of GSH led to a strong decrease of Cu(II) resistance. The precursor of GSH, ␥-glutamylcysteine (␥EC), was not able to compensate for a lack of GSH. On the contrary, ␥EC-containing cells were less copper and cadmium tolerant than cells that contained neither ␥EC nor GSH. Thus, GSH may play an important role in trace-element metabolism not only in higher organisms but also in bacteria.Under aerobic growth conditions, either glutathione (GSH; L-␥-glutamyl-L-cysteine-glycine) or the small 12-kDa protein thioredoxin (TrxB) is essential to maintain a reduced environment in the cytosol of Escherichia coli cells (5,27,60,65). Since E. coli thioredoxin reductase can transfer electrons from NADH to glutaredoxin 4 (Grx4, GrxD, or YdhD) and Grx4 can reduce Grx1 (GrxA) and Grx3 (GrxC) (14), E. coli is able to catalyze the reduction of disulfides without GSH. Thus, GSH by itself is not essential for the survival of this bacterium (17).The cellular GSH is kept almost completely reduced (2, 30): the reduced GSH-oxidized GSH (GSSG) couple has a standard redox potential at pH 7.0 of Ϫ240 mV (66). Using a potential of about Ϫ260 mV in vivo (29) and the Nernst equation results in the calculation of a GSH concentration of about 5 mM and a GSSG concentration of about 5 M. Therefore, any change in the GSH concentration is likely to influence the cellular metabolism by changing the redox potential of the cytoplasm and maybe also that of the periplasm (59). A decrease of the GSH concentration by half would increase the cytoplasmic redox potential by 18 mV.GSH is also involved in the osmoadaptation of E. coli (39). As a response to highly osmotic conditions, a mutant strain unable to synthesize trehalose as an osmoprotectant accumulates GSH to a concentration about 10-fold that under normal conditions. The first and quickest response of E. coli to changing osmotic conditions is to change the cytoplasmic potassium concentration (39), and indeed, GSH is needed for the regulation of this pool (13), probably through interaction with the GSH-gated potassium efflux system KefCYabF (43). Moreover, GSH is involved in the detoxification of methylglyoxal (13), although there are GSH-independent pathways of methylglyoxal degradation (44), and resistance to chlorine compounds (7, 67). In bacteria other than E. coli, GSH is essential for thiamine synthesis (19) and ...

show abstract

Section: Discussionmentioning

confidence: 99%

Glutathione and Transition-Metal Homeostasis inEscherichia coli

et al. 2008

View full text Add to dashboard Cite

show abstract

“…Slight differences in reported protonation constants for GSH (Table 1) did not affect the outcome of the speciation calculation at the pH of the experimental solutions so only the calculations from one set of GSH constants are shown. [15,30] …”

Section: Speciation Calculationsmentioning

confidence: 99%

“…Speciation calculations with previously determined binding constants for the Hg-DOM and Hg-GSH complexes can provide insight into the GSH titration results. Equilibrium constants for GSH protonation and for complexation of Hg with GSH have been previously reported [15,30,32] and are used here (Table 1). Complexation constants for Hg and DOM binding range by many orders of magnitude [17] and have been determined for the formation of Hg with one and two thiol functional groups in the DOM (Reactions 2, 3).…”

Section: Gsh -Reducible Hg Titrationmentioning

confidence: 99%

Competitive ligand exchange reveals time dependant changes in the reactivity of Hg–dissolved organic matter complexes

Miller

Liang

2012

Environ. Chem.

View full text Add to dashboard Cite

Environmental context. Mercury, a globally important pollutant, undergoes transformations in the environment to form methylmercury that is toxic to humans. Naturally occurring dissolved organic matter is a controller in these transformations, and we demonstrate that its strength of interaction with mercury is time dependent. These changes in complexation with dissolved organic matter are likely to affect mercury's reactivity in aquatic systems, thereby influencing how mercury is methylated and bioaccumulated.Abstract. Mercury interactions with dissolved organic matter (DOM) are important in aquatic environments but the kinetics of Hg binding to and repartitioning within the DOM remain poorly understood. We examined changes in Hg-DOM complexes using glutathione (GSH) titrations, coupled with stannous-reducible Hg measurements during Hg equilibration with DOM. In laboratory prepared DOM solutions and in water from a Hg-contaminated creek, a fraction of the Hg present as Hg-DOM complexes did not react to GSH addition. This unreactive Hg fraction increased with time from 13 % at 1 h to 74 % after 48 h of equilibration with a Suwannee River DOM. In East Fork Poplar Creek water in Oak Ridge, Tennessee, ,58 % of the DOM-complexed Hg was unreactive with GSH 1 h after the sample was collected. This timedependent increase in unreactive Hg suggests that Hg forms stronger complexes with DOM over time. Alternatively the DOM-complexed Hg may become more sterically protected from the ligand exchange reactions, as the binding environment changes within the DOM over time. These results have important implications to understanding Hg transformations in the natural environment, particularly in contaminated aquatic systems due to non-equilibrium interactions between Hg and DOM.

show abstract

“…However, the mercuric-albumin complex seems to be labile because the in vivo concentration of mercuric species in plasma decreases rapidly over time (Zalups, 1998b), suggesting that ligand exchange occurs between a mercuric-albumin complex and low-molecular-weight thiols (Zalups and Koropatnick, 2000). The low-molecular-weight thiol conjugates seem to be much less labile in an aqueous environment (Rabenstein, 1989;Farrell et al, 1990;Oram et al, 1996). In fact, administration of such thiols alters both the toxicity and disposition of Hg 2ϩ in the kidney Barfuss, 1996, 1998a;Zalups, 1998b).…”

mentioning

confidence: 99%

Human Renal Organic Anion Transporter 1-Dependent Uptake and Toxicity of Mercuric-Thiol Conjugates in Madin-Darby Canine Kidney Cells

et al. 2003

View full text Add to dashboard Cite

Mercuric ions are highly reactive and form a variety of organic complexes or conjugates in vivo. The renal proximal tubule is a primary target for mercury uptake and toxicity, and circumstantial evidence implicates organic anion transporters in these processes. To test this hypothesis directly, the transport and toxicity of mercuric-thiol conjugates were characterized in a Madin-Darby canine kidney cell line stably transfected with the human organic anion transporter 1 (hOAT1). 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-terazolium bromide assays (for mitochondrial dehydrogenase) confirmed that mercuric conjugates of the thiols N-acetylcysteine (NAC), cysteine, or glutathione were more toxic in hOAT1-transfected cells than in the nontransfected cells. The NAC-Hg 2ϩ conjugate was most cytotoxic, inducing greater than 50% cellular death over 18 h at a concentration of 100 M. The cytotoxic effects were fully reversed by probenecid (an OAT1 inhibitor) and partially reversed by p-aminohippurate (an OAT1 substrate). Toxicity of this conjugate was reduced by the OAT1-exchangeable dicarboxylates ␣-ketoglutarate, glutarate, and adipate, but not by succinate, a nonexchangeable dicarboxylate.203 Hg-uptake studies showed probenecid-sensitive uptake of mercury-thiol conjugates in the hOAT1-transfected cells. The apparent K m for the NAC-Hg 2ϩ conjugate was 44 Ϯ 9 M. Uptake of the NAC-Hg 2ϩ conjugate was cis-inhibited by glutarate, but not by methylsuccinate, paralleling their effects on toxicity. Probenecid-sensitive transport of the NAC-Hg 2ϩ conjugate was also shown to occur in Xenopus laevis oocytes expressing the hOAT1 or the rOAT3 transporters, suggesting that OAT3 may also transport thiolHg 2ϩ conjugates. Thus, renal accumulation and toxicity of thiolHg 2ϩ conjugates may depend in part on the activity of the organic transport system.

show abstract

The Formation Constants of Mercury(II)−Glutathione Complexes

Cited by 94 publications

References 15 publications

Glutathione and Transition-Metal Homeostasis inEscherichia coli

Glutathione and Transition-Metal Homeostasis inEscherichia coli

Competitive ligand exchange reveals time dependant changes in the reactivity of Hg–dissolved organic matter complexes

Human Renal Organic Anion Transporter 1-Dependent Uptake and Toxicity of Mercuric-Thiol Conjugates in Madin-Darby Canine Kidney Cells

Contact Info

Product

Resources

About