Morpholine Pathway Map

Morpholine is a common organic synthesis reactant used in many industries ranging from petroleum refining to nuclear power generation. It is also a common component of organic syntheses of many pharmaceuticals. Worldwide morpholine production is estimated at nearly 25,000 tons per year. While morpholine itself has shown little toxicity beyond slight mucous membrane irritation in rats (Harbison et al., 1989), when in the natural environment its secondary amine functionality leads inevitably to nitrosation to form N-nitrosomorpholine, a well-characterized carcinogen as described by Sielaff et al., 2001. The large-scale annual usage of morpholine and its potentially carcinogenic effects motivate investigation of the metabolic pathways involved in its biodegradation.

Morpholine degradation is completed primarily by the Mycobacterium genus. Morpholine monooxygenase is an important enzyme in this pathway (Sielaff et al., 2001). This enzyme catalyzes the biotransformation of morpholine to 2-(2-aminoethoxy) acetic acid and contains a cytochrome P450 catalytic subunit (Shaikh et al., 2009). Many different species of Mycobacterium have been shown to degrade morpholine via a shared group of degradation reactions for cyclic amines. The characterization of these reactions has been assayed by direct means but with little information about the enzymes involved in the reactions (Combourieu et al., 1998).

The following is a text-format morpholine 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 (4kb) format.

                                                        from the
                 Morpholine <----------------- N-Methylmorpholine-N-oxide      
            Mycobacterium aurum M01                      Pathway
                 and others          
                     |
                     | cytochrome p450
                     | monooxygenase 
                     | 
                     v                               
            [2-Hydroxymorpholine]      
                     |
                     |
                     | 
                     v 
       2-(2-Aminoethoxy)acetaldehyde
                     |
                     |
                     | 2-(2-aminoethoxy)acetaldehyde
                     | aldehyde dehydrogenase 
                     | 
                     v 
         2-(2-Aminoethoxy)acetate
                     |
                     |
                     v A
                     |  
                     | 
                     v 
	        Diglycolate
                     |
                     |
                     | diglycolate
                     | dehydrogenase 
                     | 
                     v 
	  Glycolate  +  Glyoxylate
              |              |
              |              |
              |              |
              |              |
              v              v
        Intermediary   Intermediary
         Metabolism     Metabolism
           (KEGG)         (KEGG)

Page Author(s): James E. Nogler, Luke Kane

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