Carboxymethylcysteine Metabolism, its Implications on Therapy in Cystinuria and on the Methionine-Cysteine Relationship

In continuation of our experiments on sulfur metabolism, the behavior of carboxy-methyl-S-cysteine 1 (I) was investigated. (We are indebted to Dr. L. Michaelis for suggesting this compound for study.) Carboxyl-methyl-S-cysteine, like methyl-S-cysteine 2 does not support the growth of rats on a sulfur deficient diet, indicating that (I) does not yield cysteine (IV) in the course of its metabolism. Three and six-tenths grams of (I) were administered to a normal human being, while 7.2 and 14.4 gm. respectively were given to 2 cystinurics. The substance was not toxic and yielded in the urine neither cystine nor -SH compounds. In the normal, the sulfur of (I) was only partially oxidized (40%), the larger portion (60%) being excreted as undetermined neutral S. Part of this neutral S was apparently a disulfide, since there appeared in the urine a strong cyanide-nitroprusside reaction, while the Sullivan test remained negative. The urine was discarded before the probable nature of this disulfide was realized. Following the ingestion of (I) by the cystinuric patients, about 15% of the extra sulfur excreted was inorganic sulfate and 85% undetermined neutral S. Cystine excretion remained practically unchanged as indicated by the Folin photometric method, 3 but when measured by the Sullivan and Lugg-Sullivan methods, it dropped from one gm. to 200 mg. per day. These various findings seemed to indicate that part of (I) was excreted presumably as the unchanged compound, that part of it was oxidized to yield inorganic sulfate, and that another portion was excreted as an intermediate which contained sulfur in the form of a disulfide linkage. As a result of previous experiments, 4 and from the chemical formula of (I), it was reasonable to assume that the excretion of a disulfide resulted from the oxidation of an -SH compound derived from carboxymethylcysteine.