Role of the transsulfuration pathway and of cystathionase activity in the formation of cysteine and sulfate from methionine in rat hepatocytes

Hepatic cystathionase activity in premature infants has been reported to be about 23% of mature levels. The possibility that premature infants require dietary cysteine because of a limited capacity for methionine transsulfuration has been suggested. To assess the extent to which low hepatic cystathionase levels affect methionine flux to cysteine in hepatocytes, the effect of inhibition of cystathionase activity with propargylglycine on the metabolism of L-({sup 35}S)methionine was determined in studies with freshly isolated rat hepatocytes. Cystathionase activity was inhibited by 25%, 42%, 63% and 76% (maximal inhibition) by treatment of hepatocytes with 2.5 {mu}M, 0.01 mM, 0.02 mM and 2 mM propargylglycine, respectively. Inhibition of cystathionase activity up to 63% had no significant effect of ({sup 35}S)glutathione, {sup 35}SO{sub 4}{sup {minus}2}S, or ({sup 35}S)cysteine formation from ({sup 35}S)methionine. However, maximal inhibition of cystathionase markedly inhibited the metabolism of ({sup 35}S)methionine to ({sup 35}S)glutathione by 93%, to {sup 35}SO{sub 4}{sup {minus}2} by 88% and to ({sup 35}S)methionine to ({sup 35}S)cystathionine accumulation in these incubation systems was 60-times control. These results with isolated rat hepatocytes suggest that the presence of less than 25% of the mature level of cystathionase activity may limit cysteine synthesis by the methionine transsulfuration pathway.