3-Nitrotyrosine (3-NTyr) is formed in vivo by the reaction of tyrosine with nitrating oxidants, superoxide and nitric acid (Beckman et al., 1992). Formation of reactive nitrogen species is presumed to play a major role in neuron death and the presence of free 3-NTyr is considered a marker for this biochemical event. It has been shown that 3-NTyr exhibits neurotoxicity when injected into rat dopaminergic cells. This neurotoxicity has been linked to the metabolism of 3-NTyr via the concerted action of the aromatic amino acid decarboxylase and monoamine oxidase. 3-Nitrotyramine is structurally similar to 3-NTyr, exhibits the same neurotoxic effects and is formed via decarboxylation of 3-NTyr in rat dopaminergic neuronal cells (Blanchard-Fillion et al., 2006). This decarboxylation has not been observed in microbes.
3-Nitrotyramine can be used as a nitrogen source by cultures of Escherichia coli utilizing a periplasmic amine oxidase (TynA) and cytosolic NAD-linked dehydrogenase (FeaB). The biodegradation pathway involves an initial oxidation to 4-hydroxy-3-nitrophenylacetaldehyde which is further oxidized to 4-hydroxy-3-nitrophenylacetate (Rankin et al., 2008). These E. coli cultures did not grow on 3-NTyr.
The metabolism of 3-NTyr in Variovorax paradoxus JS171 and Burkholderia sp. strain JS165 is carried out by deamination and subsequent decarboxylation to the above mentioned 4-hydroxy-3-nitrophenylacetate. Monooxygenase-catalyzed denitration of 4-hydroxy-3-nitrophenylacetate yields homoprotocatechuate, for which bacterial metabolism is well established (Nishino and Spain, 2006).
The following is a text-format 3-Nitrotyramine pathway map. Organism 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 (9k) format.
3-Nitrotyramine 3-Nitrotyrosine
Escherichia coli K-12 Variovorax paradoxus JS171
| Burkholderia sp. strain JS165
| |
| 3-nitrotyramine oxidase | 3-nitrotyrosine
| | transaminase
| |
v v
4-Hydroxy-3-nitrophenylacetaldehyde 4-Hydroxy-3-nitrophenylpyruvate
| |
| |
| aldehyde dehydrogenase | 4-hydroxy-3-nitrophenylpyruvate
| | oxidase
| |
| v
+----------------------------> 4-Hydroxy-3-nitrophenylacetate
|
|
| 4-hydroxy-3-nitrophenylacete
| monooxygenase
|
v
3,4-Dihydroxyphenylacetate
|
|
|
v
to the
Tyrosine
Pathway
Page Author(s): Chimezie Ononenyi and Michael Turnbull
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