THE UTILIZATION OF N-ACETYLCYSTEINE AND 2-OXOTHIAZOLIDINE-4-CARBOXYLATE BY RAT HEPATOCYTES IS LIMITED BY THEIR RATE OF UPTAKE AND CONVERSION TO CYSTEINE
Mf. Banks et Mh. Stipanuk, 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 Journal of nutrition, 124(3), 1994, pp. 378-387
N-Acetyl-L-cysteine (NAC) and L-2-oxothiazolidine-4-carboxylate (OTC)
are converted enzymatically to cysteine and have been used to stimulat
e hepatic glutathione synthesis. Using hepatocytes isolated from male
Sprague-Dawley rats and S-35-labeled substrates, the uptake and metabo
lism 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 product
ion and more rapidly than OTC for glutathione production. N-Acetyl-L-c
ysteine itself was taken up slowly by hepatocytes, but deacetylation o
f NAC to cysteine seemed to occur extracellularly. Utilization of OTC
seemed to be limited by a low rate of uptake and slow intracellular co
nversion to cysteine. The rate of accumulation of [S-35]glutathione fr
om 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 [S-35]glutathione was similar for hepatoc
ytes incubated with [S-35]cysteine or [S-35]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 expl
ained by a lower rate of substrate availability, but another unknown m
echanism also appears to favor the conversion of NAC to glutathione.