LIVER INTRACELLULAR L-CYSTEINE CONCENTRATION IS MAINTAINED AFTER INHIBITION OF THE TRANS-SULFURATION PATHWAY BY PROPARGYLGLYCINE IN RATS

To study the fate of L-cysteine and amino acid homeostasis in liver af ter the inhibition of the transsulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, l iver cystathionase (EC 4.4.1.1) activity was undetectable, L-cystathio nine levels were significantly higher, L-cysteine was unchanged and GS H concentration was significantly lower than values found in livers fr om control rats injected intraperitoneally with 0.15 M-NaCl. The hepat ic Levels of amino acids that are intermediates of the urea cycle, L-o rnithine, L-citrulline and L-arginine and blood urea were significantl y greater. Urea excretion was also higher in PPG-treated rats when com pared with control rats. These data suggest a stimulation of ureagenes is in PPG-treated rats. The inhibition of gamma-cystathionase was refl ected in the blood levels of amino acids, became the L-methionine: L-c yst(e)ine ratio was significantly higher in PPG-treated rats than in c ontrol rats; blood concentration of cystathionine was also greater. Hi stological examination of liver and kidney showed no changes in PPG-tr eated rats when compared with controls. The administration of N-acetyl cysteine (NAC) to PPG-treated rats reversed the changes in blood urea and in liver GSH. These data suggest that when liver L-cysteine produc tion was impaired by the blockage of the transsulfuration pathway, the concentration of this amino acid was maintained mainly by an increase in protein degradation and by a depletion in GSH concentration that m ay spare L-cysteine.