N-Nitrosodimethylamine Pathway Map

N-Nitrosodimethylamine (NDMA) is a byproduct of chlorination and wastewater treatment. It is a mutagen and suspected carcinogen. It volatilizes from soil very easily, and can contaminate groundwater (Yang et al. 2005). There are several studies examining mammalian degradation, but less is known about its microbial degradation.

The microbial metabolism begins when toluene-4-monooxygenase converts NDMA to N-nitrodimethylamine (NTDMA) by oxygenating the nitrogen. Several other enzymes with broad specificity, like alkane monooxygenases, can transform NDMA as well. Some example organisms include: Rhodococcus ruber ENV425P, Mycobacterium vaccae JOB5, and Methylosinus trichospoium OB3b (Sharp et al. 2005). N-Nitrodimethylamine is transformed to N-nitromethylamine (NTMA) and formaldehyde, which funnel to intermediary metabolism. Pseudomonas mendocina KR1 transformed this compound but could not grow on it or mineralize it significant amounts, suggesting the reaction is cometabolic. However, other reactions in the NDMA microbial degradation pathway are not yet understood.

NDMA is also thought to become demethylated to form methanol by an unidentified minor pathway that resembles the mammalian demethylation. Formaldehyde was shown not to be reduced to methanol in Pseudomonas KR1 (Fournier et al., 2006). Methylamine was also detected, but it is not clear whether it is a product of NTDMA, NTMA, or part of a different pathway (Kaplan et al., 1985). It is also not clear whether formaldehyde is a product of methylamine, or the result of removing a hydroxylated methyl group from NDMA, as in in the mammalian oxidative pathway, or NTDMA (depicted below), as proposed in Fournier et al., (2006).

The following is a text-format N-nitrosodimethylamine pathway map. Organisms which can initiate the pathway are given, but other organisms may also carry out later steps. Follow the links for more information on compounds or reactions. This map is also available in graphic (10k) format.

                                     N-Nitrosodimethylamine
                                   Pseudomonas mendocina KR1 
                                 Methylosinus trichosporium OB3b
                                    Mycobacterium vaccae JOB-5
                                     Ralstonia pickettii PKO1
                                               |
                                               |
                                               | toluene
                                               | 4-monooxygenase
                                               |
                                               | soluble methane monooxygenase (sMMO)
                                               |
                                               |
                                               v
                                      N-Nitrodimethylamine
                                               |
                                               |
                                               | N-nitrodimethylamine
                                               | hydroxylase
                                               |
                                               |
                                               v
                                  Formaldehyde + N-Nitromethylamine
                                        |
                                        |
                                        |
                                        |
                                        v
                                      to the
                                C1 Metabolic Cycle

Page Author(s): David Nelson and Edward LaBelle

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