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Role of the Transsulfuration Pathway and of -Cystathionase Activity in the Formation of Cysteine and Sulfate from Methionine in Rat Hepatocytes¹

Division of Nutritional Sciences, Cornell University, Ithaca, NY 14853

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-[³⁵S]methionine was determined in studies with freshly isolated rat hepatocytes. -Cystathionase activity was inhibited 25%, 42%, 63% and 76% (maximal inhibition) by treatment with 2.5 µmol/L, 0.01 mmol/L, 0.02 mmol/L and 2 mmol/L propargylglycine, respectively. Inhibition of -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 -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 -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 ß-synthase, or for methionine metabolism by an S-adenosylmethionine-independent pathway was obtained.

KEY WORDS: • -cystathionase • methionine • propargylglycine • rat hepatocytes • transsulfuration

¹ This material is based upon work supported by the Cooperative State Research Service, U.S. Department of Agriculture under Agreement No. 88-37200-3449 and by New York State Hatch Project No. 399-492.

² Author to whom reprint requests should be addressed.

Manuscript received 15 November 1989. Revision accepted 13 March 1990.

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