EurekaMag.com logo
+ 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


, : 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

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.

(PDF 0-2 workdays service)

Accession: 002530741

PMID: 8120657

Submit PDF Full Text: Here


Submit PDF Full Text

No spam - Every submission is manually reviewed

Due to poor quality, we do not accept files from Researchgate

Submitted PDF Full Texts will always be free for everyone
(We only charge for PDFs that we need to acquire)

Select a PDF file:
Close
Close

Related references

Banks M.F.; Stippanuk M.H., 1992: 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

Dizdar, N.; Kullman, A.; Kågedal, B., 2000: Comparison of N-acetylcysteine and l-2-oxothiazolidine-4-carboxylate as cysteine deliverers and glutathione precursors in human malignant melanoma transplants in mice. Purpose: Glutathione is an important cellular compound which affects detoxification of electrophiles and may have direct or indirect effects on pigment formation. It is therefore of importance to study interstitial concentrations in melanoma tissu...

Dringen, R.; Hamprecht, B., 1999: 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. The ability of neurons to metabolize sulfur-containing compounds to cysteine was investigated using as indicator the glutathione content in neuron-rich primary cultures derived from the brains of embryonal rats. The glutathione content of these cu...

Glazenburg, E.J.; Bruggink, J.E.; Wolters-Keulemans, K.; Mulder, G.J., 1984: Inhibition of glutathione efflux in the recirculating rat liver perfusion by cysteine but not by oxothiazolidine carboxylate, an intracellular cysteine precursor. In the recirculating rat liver perfusion a continuous release of glutathione into the perfusion medium is observed. Addition of L-cysteine to the perfusion medium immediately arrested this glutathione efflex. The cysteine precursor oxothiazolidine...

Gwilt, P.R.; Radick, L.E.; Li, X.Y.; Whalen, J.J.; Leaf, C.D., 1998: Pharmacokinetics of 2-oxothiazolidine-4-carboxylate, a cysteine prodrug, and cysteine. The pharmacokinetics of both 2-oxothiazolidine-4-carboxylate (OTZ), a prodrug of cysteine, and total blood cysteine (cysteine plus cystine) were investigated in 18 healthy volunteers. OTZ was given either as a single, 2-hour intravenous infusion (...

Breborowicz, A.; Patrikarea, A.; Martis, L.; Oreopoulos, D.G., 1996: L-2-Oxothiazolidine-4-carboxylate and N-acetylcysteine as precursors of intracellular glutathione in human peritoneal mesothelial cells. L-2-Oxothiazolidine-4-carboxylate and N-acetylcysteine as substrates for intracellular glutathione in human peritoneal mesothelial cells were tested. Both substances at concentrations of 0.01 mM and higher augmented the level of glutathione in mes...

Raju, P.A.; Herzenberg, L.A.; Herzenberg, L.A.; Roederer, M., 1994: Glutathione precursor and antioxidant activities of N-acetylcysteine and oxothiazolidine carboxylate compared in in vitro studies of HIV replication. N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine 4-carboxylate (OTC) are pro-GSH drugs that been proposed for AIDS therapy. In this article we compare the antiviral activities of these compounds in various in vitro HIV infection models. Although...

Baker, P.W.; Bais, R.; Rofe, A.M., 1994: The efficacy of (L)-2-oxothiazolidine-4-carboxylate (OTC) and (L)-cysteine in reducing urinary oxalate excretion. The effects of orally administered (L)-cysteine and (L)-2-oxothiazolidine-4-carboxylate (OTC) on urinary oxalate excretion were investigated in male Porton rats, as (L)-cysteine has been shown to form an adduct with glyoxylate in vitro. Feeding of...

Gwilt, P.R.; Noveck, R.J.; Radick, L.E.; Li, X.Y.; Whalen, J.J.; Leaf, C.D., 1996: Pharmacokinetics and pharmacodynamics of 2-oxothiazolidine-4-carboxylate , a cysteine prodrug, in healthy subjects. Pharmaceutical Research (New York) 13(9 SUPPL ): S487

Naya M.; Noguchi M.; Mataki Y.; Deguchi T.; Yasuda M., 1990: Effects of 1 2 oxothiazolidine 4 carboxylate a cysteine prodrug on teratogenicity of 5 fluorouracil in mice. Teratology 42(6): 43A