Modulation of endogenous synthesis of N-nitrosamino acids in humans.
Endogenous production of N-nitrosoproline (NPRO) was demonstrated in human subjects ingesting a diet low in nitrate and NPRO. The daily endogenous synthesis of NPRO was 26 +/- 10 nmol/day (mean +/- SD). Upon administration of nitrate and proline, the NPRO excreted in urine ranged from 50-318 nmol/24 h. It was found that ascorbic acid and alpha-tocopherol did not lower the background endogenous synthesis of NPRO; however, ascorbic acid was very effective in preventing the nitrate-induced synthesis of NPRO in all subjects, while alpha-tocopherol was less effective in some subjects. Furthermore, it was demonstrated that administered 15N-nitrate could be incorporated into NPRO, suggesting clearly that nitrosation reactions indeed occur in humans. Ascorbic acid significantly inhibited the incorporation of 15N-nitrate into NPRO. The presence of another N-nitrosamino acid, N-nitrosothiazolidine-4-carboxylic acid (NTCA), was detected in the urine of many subjects even without nitrate intake. However, upon ingestion of nitrate, there was a six-fold increase in mean NTCA synthesis (25 +/- 16 nmol/24 h), and all subjects had detectable levels of NTCA in the urine. Ascorbic acid completely blocked the nitrate-induced synthesis of NTCA, while alpha-tocopherol was not as effective.
D000328:Adult; D001205:Ascorbic Acid / Q000494:pharmacology*; D006801:Humans; D009602:Nitrosamines / Q000378:metabolism / Q000652:urine; D009603:Nitroso Compounds / Q000378:metabolism* / Q000652:urine; D013844:Thiazoles / Q000652:urine; D053778:Thiazolidines; D014810:Vitamin E / Q000494:pharmacology*
D009602:Nitrosamines; D009603:Nitroso Compounds; D013844:Thiazoles; D053778:Thiazolidines; D014810:Vitamin E; C040387:N-nitrosothiazolidine-4-carboxylic acid; C010259:nitrosoproline; D001205:Ascorbic Acid