+ Site Statistics
+ Search Articles
+ Subscribe to Site Feeds
EurekaMag Most Shared ContentMost Shared
EurekaMag PDF Full Text ContentPDF Full Text
+ PDF Full Text
Request PDF Full TextRequest PDF Full Text
+ Follow Us
Follow on FacebookFollow on Facebook
Follow on TwitterFollow on Twitter
Follow on Google+Follow on Google+
Follow on LinkedInFollow on LinkedIn

+ Translate

The utilization of N-acetylcysteine and 2-oxothiazolidine-4-carboxylate by rat hepatocytes is limited by their rate of uptake and conversion to cysteine

Journal of Nutrition 124(3): 378-387
The utilization of N-acetylcysteine and 2-oxothiazolidine-4-carboxylate by rat hepatocytes is limited by their rate of uptake and conversion to cysteine
N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (OTC) are converted enzymatically to cysteine and have been used to stimulate hepatic glutathione synthesis. Using hepatocytes isolated from male Sprague-Dawley rats and 35S-labeled substrates, the uptake and metabolism of these cysteine precursors was measured and compared with those for cells provided with an equimolar amount of cysteine. Cysteine was utilized more rapidly than NAC or OTC for sulfate and taurine production and more rapidly than OTC for glutathione production. N-Acetyl-L-cysteine itself was taken up slowly by hepatocytes, but deacetylation of NAC to cysteine seemed to occur extracellularly. Utilization of OTC seemed to be limited by a low rate of uptake and slow intracellular conversion to cysteine. The rate of accumulation of (35S)glutathione from OTC was low compared to that from other substrates, but glutathione production accounted for 78% of the measured OTC metabolism. Although the rate of accumulation of (35S)glutathione was similar for hepatocytes incubated with (35S)cysteine or (35S)NAC, glutathione synthesis accounted for a higher percentage of NAC metabolism than of cysteine metabolism (62-81% vs. 46%). The apparent preferential distribution of OTC and NAC to glutathione vs. taurine and sulfate can be partly explained by a lower rate of substrate availability, but another unknown mechanism also appears to favor the conversion of NAC to glutathione.

Accession: 002530741

PMID: 8120657

Related references

The utilization of n acetylcysteine nac and 2 oxothiazolidine 4 carboxylate otc by rat hepatocytes is limited by their rate of transport and conversion to cysteine cys. FASEB Journal 6(4): A1216, 1992

Comparison of N-acetylcysteine and l-2-oxothiazolidine-4-carboxylate as cysteine deliverers and glutathione precursors in human malignant melanoma transplants in mice. Cancer ChemoTherapy and Pharmacology 45(3): 192-198, 2000

N-acetylcysteine, but not methionine or 2-oxothiazolidine-4-carboxylate, serves as cysteine donor for the synthesis of glutathione in cultured neurons derived from embryonal rat brain. Neuroscience Letters 259(2): 79-82, Jan 8, 1999

Inhibition of glutathione efflux in the recirculating rat liver perfusion by cysteine but not by oxothiazolidine carboxylate, an intracellular cysteine precursor. Febs Letters 178(2): 271-274, 1984

Pharmacokinetics of 2-oxothiazolidine-4-carboxylate, a cysteine prodrug, and cysteine. Journal of Clinical Pharmacology 38(10): 945-950, 1998

L-2-Oxothiazolidine-4-carboxylate and N-acetylcysteine as precursors of intracellular glutathione in human peritoneal mesothelial cells. Blood Purification 14(1): 1-7, 1996

Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication. Aids Research and Human Retroviruses 10(8): 961-967, 1994

The efficacy of (L)-2-oxothiazolidine-4-carboxylate (OTC) and (L)-cysteine in reducing urinary oxalate excretion. Journal of Urology 152(6 Pt 1): 2139-2146, 1994

Pharmacokinetics and pharmacodynamics of 2-oxothiazolidine-4-carboxylate , a cysteine prodrug, in healthy subjects. Pharmaceutical Research (New York) 13(9 SUPPL ): S487, 1996

Effects of 1 2 oxothiazolidine 4 carboxylate a cysteine prodrug on teratogenicity of 5 fluorouracil in mice. Teratology 42(6): 43A, 1990