Stoichiometry, kinetics, and mechanisms of the chromium(VI) oxidation of L-cysteine at neutral pH

Kwong, Daniel W. J.; Pennington, David E.

doi:10.1021/ic00184a030

Cited by 49 publications

(36 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A second reduction step most likely involves the production of Cr(IV), but this has not yet been established experimentally. Cr(III)-(Cys) 2 complex was the major stable product of Cr(VI) reduction by Cys (21). Addition of DNA to the reduction mixtures resulted in the formation of Cr(III)-DNA adducts (18).…”

Section: Resultsmentioning

confidence: 99%

Reductive activation with cysteine represents a chromium(III)-dependent pathway in the induction of genotoxicity by carcinogenic chromium(VI).

Zhitkovich

Quievryn

Messer

et al. 2002

Environ Health Perspect

View full text Add to dashboard Cite

Induction of DNA damage by carcinogenic hexavalent chromium compounds [Cr(VI)] results from its reduction to lower oxidation states. Reductive metabolism of Cr(VI) generates intermediate Cr(V/IV)species, organic radicals, and finally Cr(III), which forms stable complexes with many biological ligands, including DNA. To determine the biological significance of different reaction products, we examined genotoxic responses and the formation of DNA damage during reduction of Cr(VI) by its biological reducer, cysteine. We have found that cysteine-dependent activation of Cr(VI) led to the formation of Cr-DNA and cysteine-Cr-DNA adducts as well as interstrand DNA cross-links. The yield of binary and ternary DNA adducts was relatively constant at different concentrations of Cr(VI) and averaged approximately 54 and 45%, respectively. Interstrand DNA cross-links accounted on average for 1% of adducts, and their yield was even less significant at low Cr(VI) concentrations. Reduction of Cr(VI) in several commonly used buffers did not induce detectable damage to the sugar-phosphate backbone of DNA. Replication of Cr(VI)-modified plasmids in intact human fibroblasts has shown that cysteine-dependent metabolism of Cr(VI) resulted in the formation of mutagenic and replication-blocking DNA lesions. Selective elimination of Cr-DNA adducts from Cr(VI)-treated plasmids abolished all genotoxic responses, indicating that nonoxidative, Cr(III)-dependent reactions were responsible for the induction of both mutagenicity and replication blockage by Cr(VI). The demonstration of the mutagenic potential of Cr-DNA adducts suggests that these lesions can be explored in the development of specific and mechanistically important biomarkers of exposure to toxic forms of Cr.

show abstract

Section: Resultsmentioning

confidence: 99%

Reductive activation with cysteine represents a chromium(III)-dependent pathway in the induction of genotoxicity by carcinogenic chromium(VI).

Zhitkovich

Quievryn

Messer

et al. 2002

Environ Health Perspect

View full text Add to dashboard Cite

show abstract

“…Some authors (24) have concluded that initial one-electron reduction of the Cr(V1) leads to Cr(II1) entrapment of oxidized substrate, whereas initial two-electron reduction leads to the Cr(II1) entrapment of excess substrate. If this generalization were accepted, observation of the Cr(II1)-GA complex as product implies an initial two-electron reduction of Cr(V1) by gluconic acid, such as proposed in the mechanism.…”

Section: Mechanismmentioning

confidence: 99%

Oxidation of D-gluconic acid by chromium(VI) in perchloric acid

Signorella¹,

Santoro²,

Mulero³

et al. 1994

Can. J. Chem.

View full text Add to dashboard Cite

The oxidation of gluconic acid by chromium(VI) in perchloric acid has been found to follow the rate law: −d[CrVI]/dt = (k′1 + k′2[GA])[H+]2[CrVI], where k′1 = (7.1 ± 0.2) × 10−4 M−2 s−1 and k′2 = (9.4 ± 0.2) × 10−2 M−3 s−1. This rate law corresponds to the reaction leading to the formation of 2-ketogluconic acid by C—H cleavage when a 20-fold or higher excess of acid over chromium(VI) is employed. Buildup and decay of chromium(V) intermediates accompany the decay of chromium(VI). Chromium(V) rates of decay are similar or slower than those of chromium(VI), as observed by electron paramagnetic resonance (epr) and visible spectrophotometry.

show abstract

“…Chromate, or dichromate, in fact, easily enters cells through the sulfate channel (3) and is quickly reduced by glutathione (GSH) (4), ascorbic acid (4), or cysteine (Cys) (4,5). In exposed animals, the ultimate step of the metabolic pathway yields Cr(III) inserted within the cell nucleus, where it cross-links DNA to proteins (mainly actin) or GSH (6,7).…”

mentioning

confidence: 99%

Metabolic pathways of carcinogenic chromium.

Gaggelli

Berti

D’Amelio

et al. 2002

Environ Health Perspect

View full text Add to dashboard Cite

The products of hexavalent chromium [Cr(VI)] reduction by glutathione (GSH) alone or in the presence of equimolar quantities of aspartate (Asp) and/or glutamate (Glu) and a chromium-containing material extracted from bovine liver were studied by ultraviolet-visible spectrum (UV-vis) studies, electrospray mass spectrometry (ES-MS), electron paramagnetic resonance (EPR), and nuclear magnetic resonance (NMR). Reduction of chromate by GSH was followed by UV-vis and NMR, revealing the formation of a paramagnetic complex in which GSH acts as a ligand. ES-MS and EPR measurements provided unequivocal evidence of a dimeric Cr (

show abstract

Stoichiometry, kinetics, and mechanisms of the chromium(VI) oxidation of L-cysteine at neutral pH

Cited by 49 publications

References 2 publications

Reductive activation with cysteine represents a chromium(III)-dependent pathway in the induction of genotoxicity by carcinogenic chromium(VI).

Reductive activation with cysteine represents a chromium(III)-dependent pathway in the induction of genotoxicity by carcinogenic chromium(VI).

Oxidation of D-gluconic acid by chromium(VI) in perchloric acid

Metabolic pathways of carcinogenic chromium.

Contact Info

Product

Resources

About