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(Created page with '{{BioPsy}} {{protein | Name = steroid-5-alpha-reductase, alpha polypeptide 1 | caption = | image = | width = | HGNCid = 11284 | Symbol = SRD5A1 | AltSymbols = ...')
 
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[[File:Steroidogenesis.svg|thumb|235px|right|[[Steroidogenesis]], showing both actions of 5-alpha reductase at bottom center.]]
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'''5-alpha reductase''' is an enzyme involved in steroid metabolism.
  
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'''5-Alpha reductases''', also known as '''3-oxo-5-alpha-steroid 4-dehydrogenases''', are [[enzyme]]s involved in steroid metabolism. They participate in 3 [[metabolism|metabolic pathways]]: [[bile acid]] biosynthesis, [[androgen]] and [[estrogen]] metabolism, and [[prostate cancer]].
   
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5-Alpha reductases [[catalysis|catalyze]] the following [[chemical reaction]]:
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==Function==
  
⚫
It converts [[testosterone]], the male [[sex hormone]], into the more potent [[dihydrotestosterone]]:
  
   
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:a 3-oxo-5alpha-steroid + acceptor <math>\rightleftharpoons</math> a 3-oxo-Delta<sub>4</sub>-steroid + reduced acceptor
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Thus, the two [[substrate (biochemistry)|substrates]] of these enzymes are an 3-oxo-5 alpha-steroid and acceptor, whereas its two [[product (chemistry)|products]] are 3-oxo-Delta4-steroid and a reduced acceptor.
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  ⚫
==Function==
  ⚫
5-alpha reductases convert [[testosterone]], the male [[sex hormone]], into the more potent [[dihydrotestosterone]]:
 
<gallery>
  
<gallery>
 
Image:Testosterone structure.png|[[Testosterone]].
  
Image:Testosterone structure.png|[[Testosterone]].
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Note the major difference &mdash; the Δ4,5 double-bond on the A (leftmost) ring. (The other differences between the diagrams are unrelated to chemical structure.)
  
Note the major difference &mdash; the Δ4,5 double-bond on the A (leftmost) ring. (The other differences between the diagrams are unrelated to chemical structure.)
  +
  +
These enzymes also participate in the creation of such [[neurosteroid]]s as [[allopregnanolone]] and [[Tetrahydrodeoxycorticosterone|THDOC]].
   
 
==Isoenzymes==
  
==Isoenzymes==
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There are two [[isoenzyme]]s, steroid 5-alpha reductase 1 and 2 ([[SRD5A1]] and [[SRD5A2]]).<ref name="pmid12606426">{{cite journal |author=Killian J, Pratis K, Clifton RJ, Stanton PG, Robertson DM, O'Donnell L |title=5alpha-reductase isoenzymes 1 and 2 in the rat testis during postnatal development |journal=Biol. Reprod. |volume=68 |issue=5 |pages=1711–8 |year=2003 |month=May |pmid=12606426 |doi=10.1095/biolreprod.102.009142 |url=http://www.biolreprod.org/cgi/pmidlookup?view=long&pmid=12606426}}</ref><ref name="pmid15941927">{{cite journal |author=Thiele S, Hoppe U, Holterhus PM, Hiort O |title=Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males |journal=Eur. J. Endocrinol. |volume=152 |issue=6 |pages=875–80 |year=2005 |month=June |pmid=15941927 |doi=10.1530/eje.1.01927 |url=http://eje-online.org/cgi/pmidlookup?view=long&pmid=15941927}}</ref>
  
There are two [[isoenzyme]]s, steroid 5-alpha reductase 1 and 2 ([[SRD5A1]] and [[SRD5A2]]).<ref name="pmid12606426">{{cite journal |author=Killian J, Pratis K, Clifton RJ, Stanton PG, Robertson DM, O'Donnell L |title=5alpha-reductase isoenzymes 1 and 2 in the rat testis during postnatal development |journal=Biol. Reprod. |volume=68 |issue=5 |pages=1711–8 |year=2003 |month=May |pmid=12606426 |doi=10.1095/biolreprod.102.009142 |url=http://www.biolreprod.org/cgi/pmidlookup?view=long&pmid=12606426}}</ref><ref name="pmid15941927">{{cite journal |author=Thiele S, Hoppe U, Holterhus PM, Hiort O |title=Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males |journal=Eur. J. Endocrinol. |volume=152 |issue=6 |pages=875–80 |year=2005 |month=June |pmid=15941927 |doi=10.1530/eje.1.01927 |url=http://eje-online.org/cgi/pmidlookup?view=long&pmid=15941927}}</ref>
   
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The second isoenzyme is deficient in [[5-alpha-reductase deficiency]] which leads to a form of [[intersexual]]ism.
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The second isoenzyme is deficient in [[5-alpha-reductase deficiency]], which leads to a form of [[intersexual]]ism.
   
 
==Production and inhibition==
  
==Production and inhibition==
⚫
The enzyme is produced only in specific tissues of the male human body,<ref name="pmid18473173">{{cite journal |author=Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E |title=Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice |journal=Neurochem. Res. |volume=33 |issue=10 |pages=1990–2007 |year=2008 |month=October |pmid=18473173 |doi=10.1007/s11064-008-9718-5 |url=http://dx.doi.org/10.1007/s11064-008-9718-5}}</ref> namely the [[skin]], [[seminal vesicles]], [[prostate]] and [[epididymis]].
  
   
  ⚫
The enzyme is produced only in specific tissues of the male human body,<ref name="pmid18473173">{{cite journal |author=Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E |title=Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice |journal=Neurochem. Res. |volume=33 |issue=10 |pages=1990–2007 |year=2008 |month=October |isbn=1106400897185 |pmid=18473173 |doi=10.1007/s11064-008-9718-5}}</ref> namely the [[skin]], [[seminal vesicles]], [[prostate]] and [[epididymis]].
⚫
Inhibition of 5-alpha reductase results in decreased production of DHT, increased levels of testosterone and possibly increased levels of estradiol. [[Gynecomastia]] is a possible side effect of 5-alpha reductase inhibition.
  
   
  ⚫
Inhibition of 5-alpha reductase results in decreased production of DHT, increased levels of testosterone, and, perhaps, increased levels of [[estradiol]]. [[Gynecomastia]] is a possible side-effect of 5-alpha reductase inhibition.
⚫
==Pharmacology==
  
  +
  ⚫
== Pharmacology ==
 
{{main|5-alpha-reductase inhibitor}}
  
{{main|5-alpha-reductase inhibitor}}
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[[5-alpha-reductase inhibitor]] drugs are used in [[benign prostatic hyperplasia]], [[prostate cancer]] and [[baldness]]. both isoforms are also produced in the [[brain]], where they serve to create the [[neurosteroid]] [[Allopregnenolone]] (5AR type I) and convert T to DHT(5AR type II)(1). [[Finasteride]] inhibits the function of only one of the isoenzymes (type 2), while [[dutasteride]] inhibits both forms.
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[[5-alpha-reductase inhibitor|5-Alpha-reductase inhibitor]] drugs are used in [[benign prostatic hyperplasia]], [[prostate cancer]], and [[baldness]]. Both isoforms are also produced in the [[brain]], where they serve to create the [[neurosteroid]] [[allopregnanolone]] (5AR type I) and convert T to DHT(5AR type II)(1). [[Finasteride]] inhibits the function of only one of the isoenzymes (type 2), whereas [[dutasteride]] inhibits both forms.
   
 
Research has indicated certain mushrooms have anti-5-alpha reductase activity.<ref name="Chen">
  
Research has indicated certain mushrooms have anti-5-alpha reductase activity.<ref name="Chen">
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{{Cite journal
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{{citation
  
 
| author = Chen, S., Y.C. Kao
  
| author = Chen, S., Y.C. Kao
 
| title = Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase.
  
| title = Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase.
 
| journal = The Journal of Steroid Biochemistry and Molecular Biology
  
| journal = The Journal of Steroid Biochemistry and Molecular Biology
 
| volume = 61
  
| volume = 61
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| pages = 107-115
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| pages = 107–115
 
| publisher =
 
| publisher =
 
| location = City of Hope, Duarte, California
  
| location = City of Hope, Duarte, California
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| url =
 
| url =
 
| doi =
 
| doi =
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10.1016/S0960-0760(97)80001-5| pmid =9365179
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| pmid =
 
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| issue = 3-6
 
}}</ref>
  
}}</ref>
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== Nomenclature ==
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This enzyme belongs to the family of [[oxidoreductase]]s, to be specific, those acting on the CH-CH group of donor with other acceptors. The systematic name of this enzyme class is '''3-oxo-5alpha-steroid:acceptor Delta4-oxidoreductase'''. Other names in common use include steroid
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* 5α-reductase
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* 3-oxosteroid Δ4-dehydrogenase
  +
* 3-oxo-5α-steroid Δ4-dehydrogenase
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* steroid Δ4-5α-reductase
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* Δ4-3-keto steroid 5α-reductase
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* Δ4-3-oxo steroid reductase
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* Δ4-3-ketosteroid-5α-oxidoreductase
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* Δ4-3-oxosteroid-5α-reductase
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* 3-keto-Δ4-steroid-5α-reductase
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* 5α-reductase
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* testosterone 5α-reductase
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* 4-ene-3-ketosteroid-5α-oxidoreductase
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* Δ4-5α-dehydrogenase
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* 3-oxo-5α-steroid:(acceptor) Δ4-oxidoreductase.
   
 
== References ==
  
== References ==
 
{{Reflist}}
  
{{Reflist}}
  +
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== Further reading ==
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{{refbegin}}
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* {{cite journal | author = LEVY HR, TALALAY P | date = 1959 | title = Bacterial oxidation of steroids. II. Studies on the enzymatic mechanism of ring A dehydrogenation | journal = J. Biol. Chem. | volume = 234 | pages = 2014&ndash;21 | pmid = 13673006 | issue = 8 }}
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{{refend}}
   
 
==See also==
  
==See also==
 
* [[Cholestenone 5alpha-reductase]]
  
* [[Cholestenone 5alpha-reductase]]
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* [[5-alpha-reductase_inhibitor|5α-reductase inhibitors]]
   
 
==External==
  
==External==
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{{CH-CH oxidoreductases}}
  
{{CH-CH oxidoreductases}}
 
{{Cholesterol and steroid metabolism enzymes}}
  
{{Cholesterol and steroid metabolism enzymes}}
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[[Category:EC 1.3.99]]
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[[Category:Enzymes]]
   
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{{1.3-enzyme-stub}}
  
   
 
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[[he:5-אלפא רדוקטאז]]
  
[[he:5-אלפא רדוקטאז]]
 
[[nl:5-alfa-reductase]]
  
[[nl:5-alfa-reductase]]
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[[ja:3-オキソ-5α-ステロイド-4-デヒドロゲナーゼ]]
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[[pt:5-alfa redutase]]
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[[pt:5-alfarredutase]]
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[[ru:5-альфа-редуктаза]]
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[[zh:5α還原酶]]
 
-->
  
-->
   

Latest revision as of 17:51, 14 June 2011

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steroid-5-alpha-reductase, alpha polypeptide 1
Symbol(s): SRD5A1
Locus: 5 p15
EC number 1.3.99.5
EntrezGene 6715
OMIM 184753
RefSeq NM_001047
UniProt P18405
steroid-5-alpha-reductase, alpha polypeptide 2
Symbol(s): SRD5A2
Locus: 2 p23
EC number 1.3.99.5
EntrezGene 6716
OMIM 607306
RefSeq NM_000348
UniProt P31213
File:Steroidogenesis.svg

Steroidogenesis, showing both actions of 5-alpha reductase at bottom center.

5-Alpha reductases, also known as 3-oxo-5-alpha-steroid 4-dehydrogenases, are enzymes involved in steroid metabolism. They participate in 3 metabolic pathways: bile acid biosynthesis, androgen and estrogen metabolism, and prostate cancer.

5-Alpha reductases catalyze the following chemical reaction:

a 3-oxo-5alpha-steroid + acceptor a 3-oxo-Delta4-steroid + reduced acceptor

Thus, the two substrates of these enzymes are an 3-oxo-5 alpha-steroid and acceptor, whereas its two products are 3-oxo-Delta4-steroid and a reduced acceptor.

Function

5-alpha reductases convert testosterone, the male sex hormone, into the more potent dihydrotestosterone:

Note the major difference — the Δ4,5 double-bond on the A (leftmost) ring. (The other differences between the diagrams are unrelated to chemical structure.)

These enzymes also participate in the creation of such neurosteroids as allopregnanolone and THDOC.

Isoenzymes

There are two isoenzymes, steroid 5-alpha reductase 1 and 2 (SRD5A1 and SRD5A2).[1][2]

The second isoenzyme is deficient in 5-alpha-reductase deficiency, which leads to a form of intersexualism.

Production and inhibition

The enzyme is produced only in specific tissues of the male human body,[3] namely the skin, seminal vesicles, prostate and epididymis.

Inhibition of 5-alpha reductase results in decreased production of DHT, increased levels of testosterone, and, perhaps, increased levels of estradiol. Gynecomastia is a possible side-effect of 5-alpha reductase inhibition.

Pharmacology

Main article: 5-alpha-reductase inhibitor

5-Alpha-reductase inhibitor drugs are used in benign prostatic hyperplasia, prostate cancer, and baldness. Both isoforms are also produced in the brain, where they serve to create the neurosteroid allopregnanolone (5AR type I) and convert T to DHT(5AR type II)(1). Finasteride inhibits the function of only one of the isoenzymes (type 2), whereas dutasteride inhibits both forms.

Research has indicated certain mushrooms have anti-5-alpha reductase activity.[4]

Nomenclature

This enzyme belongs to the family of oxidoreductases, to be specific, those acting on the CH-CH group of donor with other acceptors. The systematic name of this enzyme class is 3-oxo-5alpha-steroid:acceptor Delta4-oxidoreductase. Other names in common use include steroid

  • 5α-reductase
  • 3-oxosteroid Δ4-dehydrogenase
  • 3-oxo-5α-steroid Δ4-dehydrogenase
  • steroid Δ4-5α-reductase
  • Δ4-3-keto steroid 5α-reductase
  • Δ4-3-oxo steroid reductase
  • Δ4-3-ketosteroid-5α-oxidoreductase
  • Δ4-3-oxosteroid-5α-reductase
  • 3-keto-Δ4-steroid-5α-reductase
  • 5α-reductase
  • testosterone 5α-reductase
  • 4-ene-3-ketosteroid-5α-oxidoreductase
  • Δ4-5α-dehydrogenase
  • 3-oxo-5α-steroid:(acceptor) Δ4-oxidoreductase.

References

  1. ↑ Killian J, Pratis K, Clifton RJ, Stanton PG, Robertson DM, O'Donnell L (May 2003). 5alpha-reductase isoenzymes 1 and 2 in the rat testis during postnatal development. Biol. Reprod. 68 (5): 1711–8.
  2. ↑ Thiele S, Hoppe U, Holterhus PM, Hiort O (June 2005). Isoenzyme type 1 of 5alpha-reductase is abundantly transcribed in normal human genital skin fibroblasts and may play an important role in masculinization of 5alpha-reductase type 2 deficient males. Eur. J. Endocrinol. 152 (6): 875–80.
  3. ↑ Pinna G, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E (October 2008). Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressive behavior in mice. Neurochem. Res. 33 (10): 1990–2007.
  4. ↑ Chen, S., Y.C. Kao (1997). Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase.. The Journal of Steroid Biochemistry and Molecular Biology 61 (3-6): 107–115.

Further reading

  • LEVY HR, TALALAY P (1959). Bacterial oxidation of steroids. II. Studies on the enzymatic mechanism of ring A dehydrogenation. J. Biol. Chem. 234 (8): 2014–21.


See also

  • Cholestenone 5alpha-reductase
  • 5α-reductase inhibitors

External

Template:CH-CH oxidoreductases Template:Cholesterol and steroid metabolism enzymes


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