The utilization and safety of isomeric sulfur-containing amino acids in mice

Growth assays on a synthetic amino acid diet fed to mice showed that substituting D-methionine for the L-isomer resulted in a dose-dependent relative weight gain reaching approximately 76% when D-methionine was fed at a level equivalent to that optimal for the L-form. L-Cysteine and L-cystine stimulated growth in the presence of suboptimal levels of L-methionine, but D-cystine was growth depressing. L-Cystine is at least equally efficient in stimulating growth in the presence of D-methionine as in the presence of the L-isomer. Compared to a suboptimal (25% of maximum) level of L-methionine alone, supplements to this level L-methionine by N-acetyl-L-cysteine produced a weight gain of 214%; L-cysteine, 178%; L-cysteic acid, 154%; DL- + meso-lanthionine, 127%; L-cysteine sulfinic acid, 113%; D-cysteine, 76%; and S-methyl-L-cysteine, 13%. The observed growth-depressing effect of D-cysteine, D-cystine and S-methyl-L-cysteine at a concentration no greater than that optimal for methionine implies that these three sulfur-containing amino acids may be toxic. The results are discussed in terms of known and postulated transamination and transsulfuration pathways that govern the biological utilization of isomeric sulfur-containing amino acids and derivatives.