Testosterone is a naturally occurring steroid. It has a variety of medical applications, including hormone replacement therapy and treatment of osteoporosis (Gao et al., 2006), and is also widely used as a feed additive in concentrated animal feeding operations (CAFOs) (Lorenzen et al. 2005).
Sewage treatment effluent, manure spread onto agricultural fields, and pulp and paper effluent can contain high levels of androgens such as testosterone, which have the potential to contaminate freshwater supplies (Lorenzen et al. 2005). A U.S. Geological Survey study found concentrations of testosterone as high as 0.214 micrograms/L in stream water (Kolpin et al., 2002). The EPA reporting level for this steroid, which is classified as an Endocrine Disrupting Compound (EDC), is 0.005 micrograms/L.
Several bacterial species can utilize steroids such as testosterone as a sole carbon source, the best-studied being Nocardia restrictus and Comamonas testosteroni. Horinouchi et al. (2005) have documented the degradation pathway used by Comamonas testosteroni strain TA441. The pathway begins with aromatization of the A ring, followed by metacleavage. The product is then cleaved again to produce 2-hydroxyhexa-2,4-dienoate and 9,17-dioxo-1,2,3,4,10,19-hexanorandrostan-5-oate. i The degradation pathway for the latter product is not yet known, although it may be broken down via mechanisms similar to those found in fatty acid metabolism (Horinouchi et al., 2004). The former compound is converted to 4-hydroxy-2-oxohexanoate, which is probably broken down to pyruvate and propanal (Horinouchi et al., 2005).
The following is a text-format testosterone 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 format: testosterone to 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione (14k) and 3-hydroxy-9,10-secoandrosta-1,3,5(10)-triene-9,17-dione to 4-hydroxy-2-oxohexanoate (11k).
Testosterone -------------------------------------+
Comamonas testosteroni TA441 |
| |
| |
| 3beta- | 3-ketosteroid-
| hydroxysteroid | delta1-
| dehydrogenase | dehydrogenase
| |
| v
v 17beta-Hydroxyandrosta-
+-----Androst-4-ene-3,17-dione------+ 1,4-diene-3-one
| | |
| | |
| 4-AD 9alpha-hydroxylase | 3-ketosteroid- | 3beta-
| | delta1-dehydrogenase | hydroxysteroid
| | | dehydrogenase
v v |
9α-Hydroxy-4-androstene- Androsta-1,4-diene- <----------+
3-17-dione 3,17-dione
| |
| |
| 3-ketosteroid- | ADD 9alpha-hydroxylase
| delta1-dehydrogenase |
| |
| |
+-> [9alpha-Hydroxy-] <--+
[1,4-androstadiene-3,17-dione]
|
|[spontaneous cleavage]
|
v
3-Hydroxy-9,10-secoandrosta-
1,3,5(10)-triene-9,17-dione
|
|
| 3-HSA hydroxylase
|
|
v
3,4-Dihydroxy-9,10-secoandrosta-
1,3,5(10)-triene-9,17-dione
|
|
| 3,4-DHSA 4,5-dioxygenase
|
|
v
(3E,1Z)-4,5-9,10-Diseco-3-hydroxy-5,9,17-trioxoandrosta-
1(10),2-diene-4-oate
|
|
| 4,9-DSHA hydrolase
|
|
v
(2E,4E)-2-Hydroxyhexa- + 9,17-Dioxo-1,2,3,4,10,19-
2,4-dienoate hexanorandrostan-5-oate
| |
| |
| 2-hydroxyhexa-2,4- | A
| dienoate hydratase v
| |
| |
v v
4-Hydroxy-2-oxohexanoate Carbon dioxide
|
|
|
|
v
to the
p-Xylene Pathway
Page Author(s): Andrew W. Rabins and Carla Essenberg
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