THE FORMATION OF CYSTEINE FROM HOMOCYSTlWW: AND SERINE BY LIVKR TISSUE OF RATS*

Previous communications from this laboratory have presented evidence that the unsymmetrical thio ether, ZZ-S-(@-amino-~-carboxyethyl)homocysteine (cystathionine),’ may serve in lieu of cystine for the growth of rats (2) and that an enzyme is present in the liver capable of cleaving the thio ether to yield cysteine (3). Brand, in his original suggestion (4) regarding this thio ether as an intermediate in the formation of cystine from methionine, visualized the addition of homocysteine to aminoacrylic acid or its peptides with subsequent cleavage of the thio ether so formed. The hypothesis of an intermediate thio ether formation was in contrast with that of Nicolet (5) who suggested that H2S was split from homocysteine and was added to aminoacrylic acid to form cysteine. Toennies (6), on the other hand, suggested that methionine, through addition to serine, formed the methyl sulfonium derivative of the S-(p-amino-&carboxyethyl)homocysteine, which, by removal of methyl alcohol followed by cleavage, would yield cysteine. If the thio ether were the true intermediate between methionine and cystine, it seemed to us that it might be possible to bring about the conversion of homocysteine to the thio ether by allowing liver tissue of rats to act on a mixture of homocysteine plus a compound which might reasonably be expected to yield aminoacrylic acid. Since rat liver contains a system capable of cleaving the thio ether to cysteine, as we have already shown, formation of the thio ether would thus lead to the production of cysteine from homocysteine. Consequently, dl-homocysteine and dlserine were shaken anaerobically for 23 hours with slices of rat liver. Considerable extra cystine was found to be present in the neutralized,