Trans-sulfuration in mammals. The methionine-sparing effect of cystine.

1. Hepatic levels of cystathionine synthase and methionine-activating enzyme are significantly lower in rats fed a diet low in methionine and supplemented with cystine than in rats growing at the same rate while maintained on a diet adequate in methionine, with or without cystine supplementation. Cystathionase levels are also decreased, but to a smaller extent. Betaine-homocysteine methyltransferase is not affected. 2. The enzymatic activities which are lowered are restored toward normal by injections of L-methionine or L-homocysteine. 3. Methionine-activating enzyme and cystathionine synthase are inhibited in vitro by L-cystine. However, the decreased enzyme levels in the livers of rats fed the low methionine, cystine-supplemented diet cannot be attributed to either a dissociable inhibitor or cystine binding by the enzyme proteins. It seems likely that the cystine effect represents repression of enzyme synthesis. 4. The physiological meaning of these changes in enzymatic activity is briefly discussed. The changes are such that they may well explain the known “methionine-sparing” effect of cystine. 5. A possible application of these findings to the treatment of patients with homocystinuria due to cystathionine synthase deficiency is mentioned.