Thiazolidine derivatives as source of free l-cysteine in rat tissue

Włodek, Lidia; Rommelspacher, Hans; Susilo, Rudy; Radomski, Jan P.; Höfle, Gerhard

doi:10.1016/0006-2952(93)90632-7

Cited by 32 publications

(22 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The neutral pH and relatively low concentrations of cysteine found in the cell may prevent MTD from being formed (29), especially when RidA is present. Furthermore, the physiological relevance of MTD in any organism remains unclear (21,51). However, there is interest in the use of thiazolidine derivatives in therapeutic applications (21).…”

Section: Resultsmentioning

confidence: 99%

“…Furthermore, the physiological relevance of MTD in any organism remains unclear (21,51). However, there is interest in the use of thiazolidine derivatives in therapeutic applications (21). MTD and other thiazolidine derivatives can be converted to cysteine nonenzymatically or enzymatically and are viewed as a means of delivering adequate doses of cysteine to mammalian systems without causing cysteine toxicity (21).…”

Section: Resultsmentioning

confidence: 99%

“…However, there is interest in the use of thiazolidine derivatives in therapeutic applications (21). MTD and other thiazolidine derivatives can be converted to cysteine nonenzymatically or enzymatically and are viewed as a means of delivering adequate doses of cysteine to mammalian systems without causing cysteine toxicity (21). Given that cysteine behaves as a nucleophile when attacking 2AA, future studies will address the possibility that additional nucleophilic species react with 2AA in vitro.…”

Section: Resultsmentioning

confidence: 99%

“…Many prokaryotic and eukaryotic organisms are sensitive to high concentrations of cysteine (18)(19)(20)(21)(22)(23)(24). Various mechanisms have been proposed to explain cysteine toxicity, including inhibition of electron transport, inactivation of anabolic enzymes, and stimulation of Fenton chemistry, resulting in hydroxyl radical production (18,19,23,25).…”

mentioning

confidence: 99%

See 3 more Smart Citations

Endogenous Synthesis of 2-Aminoacrylate Contributes to Cysteine Sensitivity in Salmonella enterica

et al. 2014

View full text Add to dashboard Cite

RidA, the archetype member of the widely conserved RidA/YER057c/UK114 family of proteins, prevents reactive enamine/imine intermediates from accumulating in Salmonella enterica by catalyzing their hydrolysis to stable keto acid products. In the absence of RidA, endogenous 2-aminoacrylate persists in the cellular environment long enough to damage a growing list of essential metabolic enzymes. Prior studies have focused on the dehydration of serine by the pyridoxal 5=-phosphate (PLP)-dependent serine/threonine dehydratases, IlvA and TdcB, as sources of endogenous 2-aminoacrylate. The current study describes an additional source of endogenous 2-aminoacrylate derived from cysteine. The results of in vivo analysis show that the cysteine sensitivity of a ridA strain is contingent upon CdsH, the predominant cysteine desulfhydrase in S. enterica. The impact of cysteine on 2-aminoacrylate accumulation is shown to be unaffected by the presence of serine/threonine dehydratases, revealing another mechanism of endogenous 2-aminoacrylate production. Experiments in vitro suggest that 2-aminoacrylate is released from CdsH following cysteine desulfhydration, resulting in an unbound aminoacrylate substrate for RidA. This work expands our understanding of the role played by RidA in preventing enamine stress resulting from multiple normal metabolic processes.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Endogenous Synthesis of 2-Aminoacrylate Contributes to Cysteine Sensitivity in Salmonella enterica

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Such cysteine prodrugs include N-acetyl-L-cysteine (NAC) (Vinfi et al, 1980;Lauterburg et al, 1983;Ruffman and Wendel, 199l;Traber et al, 1992;Yao et al, 1994), L-2-oxothiazolidine-4-carboxylate (OTC) (Williamson et al, 1982;Porta et al, 1991), and condensation products of L-cysteine and reducing monosaccharides (Roberts et al, 1987) such as 2-(D-gluco-pentahydroxypentyl)-thiazolidine-4-carboxylic acid (D-glucose-L-cysteine, glc-cys) (Roberts et al, 1987;Gomez et al, 1994) and 2-(D-ribo-tetrahydroxybutyl)thiazolidine-4-carboxylic acid (D-ribose-L-cysteine, rib-cys) (Roberts et al, 1992). Condensation products of L-cysteine and carbonyl compounds have also been shown to act as cysteine prodrugs (Wt'odek et al, 1993). However, only a few papers on the glc-cys as a cysteine prodrug (Roberts et al, 1987;Gomez et al, 1994) have been reported.…”

Section: Introductionmentioning

confidence: 97%

Protective effect of glucose-cysteine adduct on thein situ perfused rat liver

et al. 1997

View full text Add to dashboard Cite

Summary.In situ perfusion of rat liver was performed with a medium containing glucose-cysteine adduct [2-(o-gluco-pentahydroxypentyl)-thiazolidine-4-carboxylic acid, glc-cys] and its effect on glutathione (GSH) and ATP levels and bile production was examined. The GSH content in the liver was maintained at the original level during perfusion with 1 mM glc-cys for 2 h, while it decreased significantly in the absence of glc-cys. After 4h of perfusion without glc-cys, ATP content and bile production decreased significantly besides the decrease in GSH content, but they were maintained at the original levels with glc-cys. When the perfusion was performed with the liver of rats injected with diethyl maleate (DEM), the GSH level, which was decreased to 6.0% of the control by DEM injection, was restored to 22.6% of the original level by perfusion with 2 mM glc-cys for 30 min. Data indicate that glccys is a cysteine prodrug with protective action on the liver.

show abstract

The Biochemistry of Drug Metabolism – An Introduction

Testa

Krämer

2007

Chemistry & Biodiversity

View full text Add to dashboard Cite

This review continues a general presentation of the metabolism of drugs and other xenobiotics begun in two recent issues of Chemistry & Biodiversity. This Part presents some of the numerous hydrolases involved, their nomenclature, relevant biochemical properties, catalytic mechanisms, and the many reactions of hydrolysis they catalyze. A number of medicinally, environmentally, and toxicologically relevant examples are presented and discussed. The reactions examined include the hydrolysis of carboxylic esters, amides and peptides, lactones, and other labile rings, and esters of inorganic acids. The hydration of epoxides and its enzymology are treated separately.

show abstract

Thiazolidine derivatives as source of free l-cysteine in rat tissue

Cited by 32 publications

References 53 publications

Endogenous Synthesis of 2-Aminoacrylate Contributes to Cysteine Sensitivity in Salmonella enterica

Endogenous Synthesis of 2-Aminoacrylate Contributes to Cysteine Sensitivity in Salmonella enterica

Protective effect of glucose-cysteine adduct on thein situ perfused rat liver

The Biochemistry of Drug Metabolism – An Introduction

Contact Info

Product

Resources

About