A novel role for carboxylesterase in the elevation of cellular cysteine by esters of cysteine.
Esters of cysteine, such as cysteine isopropylester (CIPE) or cysteine cyclohexylester (CCHE), are efficient delivery systems for cysteine to cells. After enzymic cleavage, the esters of cysteine provide a source of cellular cysteine, which may support reduced glutathione (GSH) synthesis and/or act as a direct chemoprotectant. Reducing esterase activity of rat lung slices or isolated hepatocytes with paraoxon or bis(4-nitrophenyl) phosphate or by reducing the temperature to 4 degrees dramatically altered the metabolism of esters of cysteine; the initial increase in cellular cysteine was slowed, the residency time of cysteine esters in the extracellular pool was prolonged without substantially enhancing the levels of intracellular ester. Incubation of lung slices with CIPE at 4 degrees led to a marked increase in cellular cysteine, which prior inhibition of esterase activity abolished. Inhibiting the neutral amino acid uptake systems, ASC and L, while effecting the uptake of cysteine, did not reduce the elevation of cellular cysteine by CIPE. We propose that the elevation of cellular cysteine by esters of cysteine may be mediated by membrane associated esterase activity.
Butterworth
M
M
MRC Toxicology Unit, University of Leicester, U.K.
Upshall
D G
DG
Cohen
G M
GM
D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000037:antagonists & inhibitors / Q000502:physiology*; D002462:Cell Membrane / Q000201:enzymology; D003511:Cyclohexanols / Q000378:metabolism; D003545:Cysteine / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000201:enzymology; D008297:Male; D008954:Models, Biological; D010261:Paraoxon / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D003511:Cyclohexanols; C083789:cyclohexyl cysteinate; C073222:cysteine isopropyl ester; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; D003545:Cysteine; D010261:Paraoxon