Role of the transsulfuration pathway and of gamma-cystathionase activity in the formation of cysteine and sulfate from methionine in rat hepatocytes.
To assess the extent to which low hepatic gamma-cystathionase levels affect methionine flux to cysteine in hepatocytes, the effect of inhibition of gamma-cystathionase activity with propargylglycine on the metabolism of L-[35S]methionine was determined in studies with freshly isolated rat hepatocytes. gamma-Cystathionase activity was inhibited 25%, 42%, 63% and 76% (maximal inhibition) by treatment with 2.5 mumol/L, 0.01 mmol/L, 0.02 mmol/L and 2 mmol/l propargylglycine, respectively. Inhibition of gamma-cystathionase activity with up to 0.02 mmol/L propargylglycine had no statistically significant effect on [35S]glutathione, [35S]sulfate or [35S]cysteine formation from [35S]methionine. However, treatment of cells with 2 mmol/L propargylglycine markedly inhibited the metabolism of [35S]methionine to [35S]glutathione by 93%, to [35S]sulfate by 88% and to [35S]cysteine by 89%; [35S]cystathionine accumulation in these incubation systems was 60 times control. Hepatic gamma-cystathionase activity in premature infants has been reported to be about 23% of mature levels (Zlotkin and Anderson, 1982; Pediatr. Res. 16: 65-68); this level of gamma-cystathionase activity may limit cysteine synthesis by the methionine transsulfuration pathway. No evidence for cysteine synthesis from serine and sulfide, which can be catalyzed by cystathionine beta-synthase, or for methionine metabolism by an S-adenosylmethionine-independent pathway was obtained.
Rao
A M
AM
Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853.
Drake
M R
MR
Stipanuk
M H
MH
D000480:Alkynes; D000818:Animals; D003542:Cystathionine gamma-Lyase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D005998:Glycine / Q000031:analogs & derivatives / Q000494:pharmacology; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008190:Lyases / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism*; D010293:Pargyline / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000378:metabolism; D013431:Sulfates / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D013654:Taurine / Q000378:metabolism
D000480:Alkynes; D013431:Sulfates; D013462:Sulfur Radioisotopes; D013654:Taurine; D012694:Serine; C009055:propargylglycine; D010293:Pargyline; D008715:Methionine; D008190:Lyases; D003542:Cystathionine gamma-Lyase; D005978:Glutathione; D003545:Cysteine; D005998:Glycine