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 after the inhibition of the trans-sulfuration pathway, rats were treated with propargylglycine (PPG). At 4 h after the administration of PPG, liver cystathionase (EC 4.4.1.1) activity was undetectable, L-cystathionine levels were significantly higher, L-cysteine was unchanged and GSH concentration was significantly lower than values found in livers from control rats injected intraperitoneally with 0.15 M-NaCl. The hepatic levels of amino acids that are intermediates of the urea cycle, L-ornithine, L-citrulline and L-arginine and blood urea were significantly greater. Ura excretion was also higher in PPG-treated rats when compared with control rats. These data suggest a stimulation of ureagenesis in PPG-treated rats. The inhibition of gamma-cystathionase was reflected in the blood levels of amino acids, because the L-methionine: L-cyst(e)ine ratio was significantly higher in PPG-treated rats than in control rats; blood concentration of cystathionine was also greater. Histological examination of liver and kidney showed no changes in PPG-treated rats when compared with controls. The administration of N-acetylcysteine (NAC) to PPG-treated rats reversed the changes in blood urea and in liver GSH. These data suggest that when liver L-cysteine production was impaired by the blockage of the trans-sulfuration pathway, the concentration of this amino acid was maintained mainly by an increase in protein degradation and by a depletion in GSH concentration that may spare L-cysteine.
Triguero
A
A
Departamento de Bioquímica y Biología Molecular, Universidad de Valencia, Spain.
Barber
T
T
García
C
C
Puertes
I R
IR
Sastre
J
J
Viña
J R
JR
D000111:Acetylcysteine / Q000494:pharmacology; D000480:Alkynes / Q000494:pharmacology*; D000818:Animals; D003540:Cystathionine / Q000097:blood / Q000378:metabolism*; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors*; D003545:Cysteine / Q000097:blood / Q000378:metabolism*; D003864:Depression, Chemical; D005978:Glutathione / Q000378:metabolism*; D005998:Glycine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014508:Urea / Q000652:urine
D000480:Alkynes; D003540:Cystathionine; C009055:propargylglycine; D014508:Urea; D008715:Methionine; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D003545:Cysteine; D005998:Glycine; D000111:Acetylcysteine