Reactions between Mercuric Mercury and Cysteine and Glutathione. Apparent Dissociation Constants, Heats and Entropies of Formation of Various Forms of Mercuric Mercapto-Cysteine and -Glutathione

Stricks, W.; Kolthoff, I. M.

doi:10.1021/ja01118a060

Cited by 208 publications

(112 citation statements)

References 11 publications

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“…Although GSH is the most difficult of the present systems to quantify, being the most easily oxidized and having the most ionisable protons, the agreement among the various studies is very good, except for the early work of Stricks and Kolthoff. 44 The agreement between the present results and those of Crea et al 17 obtained under almost identical conditions in NaCl and in 1.0 M (KCl) is particularly gratifying. 28 To the best of our knowledge this is the first time that this has been achieved: previous studies have mostly been measured over very restricted concentration ranges, sometimes at only one pH.…”

Section: Protonation Constantssupporting

confidence: 89%

Formation constants of copper(i) complexes with cysteine, penicillamine and glutathione: implications for copper speciation in the human eye

Königsberger

Hefter

et al. 2015

Dalton Trans.

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Protonation constants for the biologically-important thioamino acids cysteine (CSH), penicillamine (PSH) and glutathione (GSH), and the formation constants of their complexes with Cu(I), have been measured at 25 C and an ionic strength of 1.00 mol dm 3 (Na)Cl using glass electrode potentiometry. The first successful characterisation of binary Cu(I)CSH and Cu(I)GSH species over the whole pH range was achieved in this study by the addition of a second thioamino acid, which prevented the precipitation that normally occurs. Appropriate combinations of binary and ternary (mixed ligand) titration data were used to optimise the speciation models and formation constants for the binary species. The results obtained differ significantly from literature data with respect to the detection and quantification of protonated and polynuclear complexes. The present results are thought to be more reliable because of the exceptionally wide pH and concentration ranges employed, the excellent reproducibility of the data, the close agreement between the calculated and observed formation functions, and the low standard deviations and absence of numerical correlation in the constants. The present formation constants were incorporated into a large Cu speciation model which was used to predict, for the first time, metal-ligand equilibria in the biofluids of the human eye. This simulation provided an explanation for the precipitation of metallic copper in lens and cornea, which is known to occur as a consequence of Wilson's disease.

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Section: Protonation Constantssupporting

confidence: 89%

Formation constants of copper(i) complexes with cysteine, penicillamine and glutathione: implications for copper speciation in the human eye

Königsberger

Hefter

et al. 2015

Dalton Trans.

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“…The maximum concentration of heavy metal contamination would be 3-4 #M if all the impurities consisted exclusively of Ni2+, the metal with the lowest molecular weight, and the minimum would be 0-8 JtM if the impurities consisted exclusively of Pb2+, the highest molecular weight metal that is likely to contaminate the solutions. The ion-exchange column can reduce the heavy metal concentrations by at least a factor of 100 such that of the total (bound and free) concentration of heavy metal contaminants was conservatively estimated at less than 10-8 M. (Stricks & Kolthoff, 1953). Thus, nearly all the added heavy metals diffusing into the cytosol were probably bound to SH sites on muscle proteins.…”

Section: Determination Offree Heavy Metal Concentrationsmentioning

confidence: 99%

Sulphydryl reagents trigger Ca2+ release from the sarcoplasmic reticulum of skinned rabbit psoas fibres.

Salama

Abramson

Pike

1992

The Journal of Physiology

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SUMMARY1. By analogy with studies on sarcoplasmic reticulum (SR) vesicles, Ca2+ release induced by heavy metals and mercaptans (e.g. cysteine) was investigated in rabbit skinned psoas fibres through measurements of isometric tension.2. Heavy metals (at 2-5 /tM) elicited phasic contractions by triggering Ca2+ release from the SR and had the following order of potency: Hg2+ > Cu2+ > Cd2+ > Ag+ > Ni2+. Higher concentrations produced tonic contractions due to maintained high Ca2+ permeability of SR membranes.3. Contractions induced by heavy metals required a functional and Ca2+-loaded SR, were dependent on [Ca2+]free, blocked by Ruthenium Red (RR), inhibited by free Mg2+ and reduced glutathione (GSH) but not by oxidized glutathione (GSSG). Such contractions were not elicited through direct interactions) of heavy metals with the myofilaments.4. In the presence of catalytic concentrations of Hg2+ or Cu2+ (2-5 /UM), additions of cysteine (25-100 /LM) elicited rapid twitches, producing 70 % of maximal force with a time to half-peak of 2 s. Contractions induced by cysteine plus a catalyst required a functional SR network, were dependent on free [Mg2+] and were blocked by RR or GSH but not by GSSG.5. In the presence of Hg2+ (2-5 ,uM), low concentrations of cysteine (10 /uM) elicited tonic contractures, but subsequent or higher additions of cysteine (50-100 uM) caused further SR Ca2+ release and tension, followed by rapid and full relaxation.6. High cysteine (200-250 /tM, without Cu2+ or Hg2+) blocked contractions elicited by Cl-induced depolarization of sealed T-tubules. High cysteine probably acted as a sulphydryl reducing agent which promoted rapid relaxation of the fibres through the closure of Ca2+-release channels and ATP-dependent re-uptake of Ca2+ by the SR. 7. In some batches of skinned fibres (-10%), cysteine (5-50 /tM) alone (without Hg2+ or Cu2+ catalyst) produced rapid twitches. This implied that the catalysts) necessary to promote the sulphydryl oxidation reaction with exogenously added cysteine may be present in intact fibres but is usually lost by the skinning procedure.

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“…We point out that, if Hg-or Ag:(y-GluCys)n-Gly mercaptide complexes are formed in vivo, then, owing to their stability, they would probably escape detection by standard methods that detect GSH and phytochelatins on the basis of reactive sulfhydryl groups (see GSH assay in "Materials and Methods"). Because Cd-GSH complexes are many orders of magnitude less stable than Ag-or Hg-GSH complexes (4,22,35), it is interesting to speculate that the unique potency of Cd>2 as an inducer of phytochelatin synthesis and accumulation may reflect an evolutionary adaptation of the organism to the inability of GSH to effectively bind Cd>2 ions with the stability required for Cd24 detoxification. In support of this idea is the fact that the affinity of Cd>2 to ('y-Glu-Cys)n-Gly peptides of length n = 1 (GSH), 2, and 3 increases significantly with increasing peptide length (14).…”

Section: Competition Between Ag+ and Cu2+mentioning

confidence: 99%

“…Although the n = 2 phytochelatin peptides may well be responsible for chelation of intracellular Hg24 ions, an alternative but perhaps more straightforward possibility is that GSH itself, rather than phytochelatins, could be a ligand for Hg24 ions. The high stability of Hg(GSH)2 mercaptide complexes at physiological pH (Kd = l0"') (35) suggests that GSH could function as an extremely effective scavenger of Hg2+ ions, and perhaps Ag+ ions, in vivo. Although GSH has been implicated as a mechanism for detoxification of Cd2+ and Cu2+ ions in animal cells (7,32), little attention has been paid to the possibility that this peptide could serve a similar function in plants.…”

Section: Competition Between Ag+ and Cu2+mentioning

confidence: 99%

Heavy Metal-Activated Synthesis of Peptides in Chlamydomonas reinhardtii

Howe¹,

Merchant²

1992

Plant Physiol.

144

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In this study, we have addressed the capacity of the green alga Chiamydomonas reinhardtii to produce metal-binding peptides in response to stress induced by the heavy metals Cd2 , Hg2+, and Ag+. Cells cultured in the presence of sublethal concentrations of Cd2+ synthesized and accumulated oligopeptides consisting solely of glutamic acid, cysteine, and glycine in an average ratio of 3:3:1. Cadmium-induced peptides were isolated in their native form as higher molecular weight peptide-metal complexes with an apparent molecular weight of approximately 6.5 x 103. The isolated complex bound cadmium (as evidenced by absorption spectroscopy) and sequestered (with a stoichiometry of 0.7 moles of cadmium per mole of cysteine) up to 70% of the total cadmium found in extracts of cadmium-treated cells. In Hg2+-treated cells, the principal thiol-containing compound induced by Hg2 ions was glutathione. It is possible that glutathione functions in plant cells (as it does in animal cells) to detoxify heavy metals. Cells treated with Ag+ ions also synthesized a sulfur-containing component with a charge to mass ratio similar to Cd2+-induced peptides. But, in contrast to the results obtained using Cd2 as an inducer, these molecules did not accumulate to significant levels in Ag+-treated cells. The presence of physiological concentrations of Cu2+ in the growth medium blocked the synthesis of the Ag+-inducible component(s) and rendered cells resistant to the toxic effects of Ag+, suggesting competition between Cu2+ and Ag+ ions, possibly at the level of metal uptake.Many organisms respond to the cytotoxic effects of heavy metals by synthesizing metal-chelating proteins or peptides. The predominant class of such molecules in plants, algae, and some fungi are the small, cysteine-rich peptides referred to as phytochelatins (12), Cd2+-binding peptides (25), cadystins (19), or -y-glutamyl peptides (29). These molecules have the general structure (,y-Glu-Cys)n-Gly (12,17,20,34), where n can range from 2 to 11 depending on the species from which the peptides are isolated and the conditions of their induction (10,13 tionally activated, metal-dependent, enzymatic pathway from precursor GSH (13,30,31,34). This view is supported by genetic evidence showing that yeast cells with defects in the GSH biosynthetic pathway fail to accumulate phytochelatins in response to heavy metal stress (26). Elucidation of the pathway for the biosynthesis of phytochelatins in vascular plants has recently culminated with the identification of a "phytochelatin synthase" activity in suspension cultures of Silene cucubalus (1 1). The isolated enzyme has a heavy metaldependent y-glutamylcysteine dipeptidyl transpeptidase activity that is proposed to be responsible for the metal-regulated biosynthesis of phytochelatins in vivo. The further characterization of phytochelatin synthase will provide a focal point for the study of the biosynthetic regulation and physiological function(s) of these novel peptides.The phytochelatin response pathway in plants presumably ...

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Reactions between Mercuric Mercury and Cysteine and Glutathione. Apparent Dissociation Constants, Heats and Entropies of Formation of Various Forms of Mercuric Mercapto-Cysteine and -Glutathione

Cited by 208 publications

References 11 publications

Formation constants of copper(i) complexes with cysteine, penicillamine and glutathione: implications for copper speciation in the human eye

Formation constants of copper(i) complexes with cysteine, penicillamine and glutathione: implications for copper speciation in the human eye

Sulphydryl reagents trigger Ca2+ release from the sarcoplasmic reticulum of skinned rabbit psoas fibres.

Heavy Metal-Activated Synthesis of Peptides in Chlamydomonas reinhardtii

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