The metabolism of sulfur; the distribution of urinary sulfur and the excretion of keto acids after the oral administration of some derivatives of cystine and methionine to the rabbit.

The enzymatic systems which effect the biological degradation of the sulfur-containing amino acids of the protein molecule, cystine and methionine, are not well understood. Knowledge of the intermediary stages in the metabolism of these amino acids is also lacking. When either of these amino acids is administered orally or parenterally in moderate amounts to the more common laboratory animals (cat, dog, rabbit, or rat), the sulfur is excreted almost exclusively as oxidized (sulfate) sulfur in the urine, and slight increases only in the organic sulfur fraction of the urine are observed. It is generally believed that a primary change in the metabolism of the naturally occurring amino acids is oxidative deamination; enzyme systems which accomplish this oxidation have been described (l), and the products of such deamination have been isolated, not only in in vitro experiments with tissue slices (2) but also from the urine of experimental animals to which amino acids were administered (3). The keto acid derived from the oxidative deamination of methionine has been thus characterized but, so far as is known to us, the corresponding derivative of cystine has not been identified as a product of the intermediary metabolism of this amino acid. A second problem of catabolism must be considered also in the study of the sulfur-containing amino acids; i.e., the oxidation of the sulfur. Does oxidation of the sulfur occur prior to oxidative deamination? What is the relation, if any, between oxidative deamination and oxidation of the sulfur? One of us (L.) has shown that if the deamination of the amino group of cystine (4, 5) or methionine (6) is interfered with by “blocking” the amino group with a group difficult to remove biologically (phenylureido or benzoyl), the o-xidation of the sulfur does not occur normally. When these compounds were administered to rabbits, no significant increase in the oxidized (sulfate) sulfur of the urine was observed and the sulfur of the compounds administered appeared largely in the organic sulfur fraction of the urine. This relative stability of the sulfur in derivatives of cystine or