Ibuprofen is the third highest consumed drug in the world and has analgesic, antipyretic, and anti-inflammatory properties in the body (Murdoc and Hays, 2005). Kolpin et al. (2002) found ibuprofen in about 10% of US streams studied.
Sphingomonas sp. strain Ibu-2 can use ibuprofen as the sole source of carbon and energy. Isobutylcatechol and the two metabolites following it below were detected, suggesting that the propanoate side chain was removed prior to ring cleavage (Murdoc and Hays, 2005). Further work determined that five genes, ipfABDFE, participate in ibuprofen catabolism. The degradation pathway starts by transferring Coenzyme A onto ibuprofen with the help of ATP. A dixoygenase forms cis-1,2-diol-2-hydroibuprofen-CoA. A thiolase then forms isobutylcatechol and propanoyl-CoA. This is the first report of a thiolase rather than a dehydrogenase forming such a catechol from a di- or monohydrodiol. Meta-cleavage of the isobutylcatechol produces 5-formyl-2-hydroxy-7-methylocta-2,4-dienoic acid, which then forms 2-hydroxy-5-isobutylhexa-2,4-dienedioic acid (Kagle et al., 2009).
The following is a text-format ibuprofen pathway map. An organism which can initiate the pathway is 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.
Ibuprofen
Sphingomonas sp. Ibu-2
|
|
| ibuprofen--CoA
| ligase
|
v
Ibuprofen-CoA
|
|
| ibuprofen-CoA
| 1,2-dioxygenase
|
v
[cis-1,2-Diol-2-hydroibuprofen-CoA]
|
|
| cis-1,2-diol-2-hydro-
| ibuprofen-CoA thiolase
|
v
Isobutylcatechol + Propanoyl-CoA ------------> to Intermediary
| Metabolism
| (KEGG)
| isobutylcatechol
| 2,3-dioxygenase
|
v
5-Formyl-2-hydroxy-7-methyl-
octa-2,4-dienoate
|
| 5-formyl-2-hydroxy-7-methyl-
| octa-2,4-dienoate
| dehydrogenase
|
v
2-Hydroxy-5-isobutyl-
hexa-2,4-dienoate
Page Author(s): Lynda Ellis
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