Summary auto-generated
This study investigated how bacteria catalyze the formation of N-nitrosomorpholine (NMOR), a carcinogenic nitrosamine, from morpholine and nitrite at neutral pH. Researchers examined four bacterial species and multiple E. coli mutants to identify which enzymes drive this nitrosation process. The key finding was that nitrate reductase, a molybdenum-containing enzyme, is essential for bacterial nitrosation—not nitrite reductase as previously suspected. In non-denitrifying bacteria like E. coli and Proteus morganii, nitrosating activity was induced during anaerobic growth with nitrate but inhibited by tungsten, a molybdenum analogue. However, denitrifying bacteria showed different induction patterns: Pseudomonas aeruginosa required either nitrate or nitrite anaerobically, while Paracoccus denitrificans preferred nitrate. These findings are medically relevant because endogenous formation of carcinogenic N-nitroso compounds by intestinal and urinary bacteria has been linked to increased cancer risk in the stomach and bladder. The research clarifies the enzymatic mechanisms underlying bacterial nitrosation, which could inform strategies to reduce cancer risk from this endogenous source.
Key findings
- Nitrate reductase, not nitrite reductase, is the essential enzyme for bacterial nitrosation of secondary amines like morpholine
- Nitrosating activity in non-denitrifying bacteria (E. coli, Proteus morganii) requires anaerobic culture with nitrate and is inhibited by tungsten, a molybdenum analogue
- Denitrifying bacteria exhibit different induction requirements: Pseudomonas aeruginosa is induced by either nitrate or nitrite anaerobically, while Paracoccus denitrificans prefers anaerobic conditions with nitrate
- Bacterial nitrosation capacity correlates with nitrate reductase activity but not with any of the three types of nitrite reductase examined
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Abstract
SUMMARY: Biochemical, microbiological and genetic studies were done to characterize the mechanism of bacterial formation of N-nitrosomorpholine (NMOR) from morpholine and nitrite at neutral pH. In Escherichia coli and Proteus morganii, the nitrosating activity was markedly induced when bacteria were cultured under anaerobiosis in minimal medium containing nitrate, while in the presence of nitrite there was no induction. However, induction of the nitrosating activity in Pseudomonas aeruginosa occurred in anaerobic cultures in the presence of either nitrate or nitrite. The nitrosation capacity was also examined in various E. coli K12 mutants whose structural gene of either nitrate reductase or nitrite reductase was deleted. Nitrosation was not linked to the three (NADH-, formate- and glucose-dependent) nitrite reductases but was directly dependent on the presence of a nitrate reductase.