Roles of cysteine as both precursor of thiazolidine 4-carboxylic acids found in human urine and possible inhibitor of endogenous N-nitrosation.
In order to compare the utility and significance of 2-R-N-nitrosothiazolidine 4-carboxylic acids excreted in human urine as an index for exposure to N-nitroso compounds, the differences in formation of N-nitrosothiazolidine 4-carboxylic acid (NTCA; R = H) and N-nitroso-2-methylthiazolidine 4-carboxylic acid (NMTCA; R = CH3) were studied in vitro. It was determined that NMTCA has a 3:1 trans:cis stereoisomer ratio, while NTCA has a 1:1 trans:cis ratio; nitrosation acts on a pH-dependent equilibrium mixture of cysteine and aldehyde in equilibrium with thiazolidine 4-carboxylic acid, with cysteine blocking N-nitrosation. Previous reports on 2-R-N-nitrosothiazolidine 4-carboxylic acids in human urine show widespread involvement of cysteine, which has a dual role with nitrosating species. In view of this and the rapid blocking of N-nitrosation and slow trans-nitrosation by cysteine at acid pH, it is suggested that there may be a hitherto unrecognized protective role of thiol functions in dietary constituents.
O'Neill
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IK
International Agency for Research on Cancer, Lyon, France.
Ohshima
H
H
D003545:Cysteine / Q000378:metabolism*; D005583:Fourier Analysis; D006801:Humans; D066298:In Vitro Techniques; D009682:Magnetic Resonance Spectroscopy; D009603:Nitroso Compounds / Q000096:biosynthesis* / Q000652:urine; D013844:Thiazoles / Q000096:biosynthesis* / Q000652:urine; D053778:Thiazolidines
C041920:N-nitroso-2-methylthiazolidine-4-carboxylic acid; D009603:Nitroso Compounds; D013844:Thiazoles; D053778:Thiazolidines; C040387:N-nitrosothiazolidine-4-carboxylic acid; D003545:Cysteine