Methionine metabolism in mammals. The methionine-sparing effect of cystine

Cystine can replace approximately 70% of the dietary requirement for methionine. We used standard enzyme assays, determinations of the hepatic concentrations of metabolites and an in vitro system which simulates the regulatory site formed by the enzymes which utilize homocysteine in this study of the mechanism for this adaptation. A significant alteration in the pattern of hepatic homocysteine metabolism occurs following the substitution of cystine for methionine. The major change is a marked reduction in the synthesis of cystathionine. Decreases in both the level of cystathionine synthase and in the concentration of adenosyl-methionine, a positive effector of the enzyme, explain this finding. Despite significant increases in the hepatic levels of betaine-homocysteine methyltransferase and methyltetrahydrofolate-homocysteine methyltransferase, flow through these reactions remains relatively constant. The betaine enzyme may be essential for efficient methionine conservation. In the absence of choline, cystine cannot replace methionine in an adequate diet limited in the latter amino acid.