Presence in human urine of new sulfur-containing N-nitrosamino acids: N-nitrosothiazolidine 4-carboxylic acid and N-nitroso 2-methylthiazolidine 4-carboxylic acid

A new type of sulfur-containing N-nitrosamino acid, N-nitrosothiazolidine 4-carboxylic acid (NTCA) and N-nitroso 2-methylthiazolidine 4-carboxylic acid (NMTCA), was isolated and identified in the urine of human subjects. Identification was based on identical chromatographic and mass spectral data for the purified urine sample and the synthesized authentic compounds. The amounts of NTCA and NMTCA excreted in 24-h urines of 15 volunteers varied from 0.9 to 35.9 micrograms/day and from 0.4 to 19.8 micrograms/day, respectively. These amounts were 2.4 and 1.6 times greater than that of N-nitrosoproline (NPRO) detected in the same urine samples. Thiazolidine 4-carboxylic acid and its 2-methyl derivative were found to be nitrosated in vitro about 250-500 and 60-300 times more rapidly than proline, respectively. In addition, NTCA and NMTCA were also readily formed by reaction of a mixture of nitrite and L-cysteine, with formaldehyde and acetaldehyde, respectively. Although their origin in human urine is unknown, preliminary results in one human volunteer have shown that some of these compounds are formed endogenously. Thus, measurement of these new sulfur-containing N-nitrosamino acids in the urine may (i) provide another index for endogenous nitrosation reactions in the human body and (ii) allow monitoring of exposure of humans to precursors such as aldehydes and nitrate/nitrite.