'''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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==Function==
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5-Alpha reductases [[catalysis|catalyze]] the following [[chemical reaction]]:
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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==
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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.)
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.)
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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==
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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]].
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Inhibitionof5-alphareductaseresults in decreasedproduction of DHT, increasedlevelsoftestosterone and possiblyincreasedlevelsofestradiol. [[Gynecomastia]]isapossiblesideeffectof5-alphareductaseinhibition.
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Theenzymeisproducedonly in specifictissues of the male human body,<refname="pmid18473173">{{citejournal|author=PinnaG, Agis-Balboa RC, Pibiri F, Nelson M, Guidotti A, Costa E |title=Neurosteroid biosynthesis regulates sexually dimorphic fear and aggressivebehaviorinmice|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>namelythe [[skin]], [[seminal vesicles]], [[prostate]] and [[epididymis]].
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==Pharmacology==
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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.
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== 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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{{citation
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{{Cite journal
| 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
Line 76:
Line 84:
| url =
| url =
| doi =
| doi =
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| pmid =
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10.1016/S0960-0760(97)80001-5| pmid =9365179
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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
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* 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 = 2014–21 | pmid = 13673006 | issue = 8 }}
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.
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.)
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.
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
↑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.
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Chen, S., Y.C. Kao (1997). Binding characteristics of aromatase inhibitors and phytoestrogens to human aromatase.. The Journal of Steroid Biochemistry and Molecular Biology61 (3-6): 107–115.
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.
a 3-oxo-Delta4-steroid + reduced acceptor
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