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2013-06-17T14:53:21Z

67.160.69.105: uncapitalize

{{enzyme
| EC_number = 1.1.1.145
| IUBMB_EC_number = 1/1/1/145
| CAS_number= 9044-85-3
| Name = 3β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase
| GO_code = 0003854
| image =
| width =
| caption =
}}
{{infobox protein
| Name = [[HSD3B1|hydroxy-Δ-5-steroid dehydrogenase, 3β- and steroid Δ-isomerase 1]]
| caption =
| image =
| width =
| HGNCid = 5217
| Symbol = [[HSD3B1]]
| AltSymbols = HSDB3, HSD3B
| EntrezGene = 3283
| OMIM = 109715
| RefSeq = NM_000862
| UniProt = P14060
| PDB =
| ECnumber = 1.1.1.145
| Chromosome = 1
| Arm = p
| Band = 13
| LocusSupplementaryData = -p11
}}
{{infobox protein
| Name = [[HSD3B2|hydroxy-Δ-5-steroid dehydrogenase, 3β- and steroid Δ-isomerase 2]]
| caption =
| image =
| width =
| HGNCid = 5218
| Symbol = [[HSD3B2]]
| AltSymbols =
| EntrezGene = 3284
| OMIM = 613890
| RefSeq = NM_000198
| UniProt = P26439
| PDB =
| ECnumber = 1.1.1.145
| Chromosome = 1
| Arm = p
| Band = 13.1
| LocusSupplementaryData =
}}
'''3-β-HSD''' (or '''3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase''') ({{EC number|1.1.1.145}}) is an [[enzyme]] that [[catalysis|catalyzes]] the synthesis of [[progesterone]] from [[pregnenolone]], 17-hydroxyprogesterone from 17-hydroxypregnenolone, and [[androstenedione]] from [[dehydroepiandrosterone]] in the adrenal gland. It is the only enzyme in the adrenal pathway of [[corticosteroid]] synthesis that is not a member of the [[Cytochrome P450]] family.<ref name="pmid3088022">{{cite journal | author = Cravioto MD, Ulloa-Aguirre A, Bermudez JA, Herrera J, Lisker R, Mendez JP, Perez-Palacios G | title = A new inherited variant of the 3 beta-hydroxysteroid dehydrogenase-isomerase deficiency syndrome: evidence for the existence of two isoenzymes | journal = J. Clin. Endocrinol. Metab. | volume = 63 | issue = 2 | pages = 360–7 |date=August 1986 | pmid = 3088022 | doi = 10.1210/jcem-63-2-360| url = }}</ref> In humans, there are two 3-β-HSD [[isozyme]]s encoded by the [[HSD3B1]] and [[HSD3B2]] genes.

It is also known as delta 5-delta 4-isomerase, which catalyzes the oxidative conversion of delta 5-3 beta- [[hydroxysteroid]]s to the delta 4-3-keto configuration and is, therefore, essential for the [[biosynthesis]] of all classes of [[hormonal]] [[steroid]]s, namely [[progesterone]], [[glucocorticoids]], [[mineralocorticoids]], [[androgen]]s, and [[estrogen]]s.<ref name="pmid1737804">{{cite journal | author = Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guérin S, Leblanc G, Labrie F | title = Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells | journal = J. Biol. Chem. | volume = 267 | issue = 5 | pages = 3551 |date=February 1992 | pmid = 1737804 | doi = | url = }}</ref>
The 3-beta HSD complex is responsible for the conversion of:

* [[pregnenolone]] to [[progesterone]]
* 17-alpha-pregnenolone to 17-alpha-progesterone
* dehydroepiandrosterone ([[DHEA]]) to [[androstenedione]]
* [[androstenediol]] to [[testosterone]]

== Reaction ==

3-β-HSD belongs to the family of [[oxidoreductase]]s, to be specific, those acting on the CH-OH group of donor with NAD+ or NADP+ as acceptor. This enzyme participates in c21-steroid hormone metabolism and androgen and estrogen metabolism.

3-β-HSD [[catalysis|catalyzes]] the [[chemical reaction]]:

:a 3β-hydroxy-Δ5-steroid + NAD+ <math>\rightleftharpoons</math> a 3-oxo-Δ5-steroid + NADH + H+

Thus, the two [[substrate (biochemistry)|substrates]] of this enzyme are 3β-hydroxy-Δ5-steroid and [[nicotinamide adenine dinucleotide|NAD+]], whereas its 3 [[product (chemistry)|products]] are 3-oxo-Δ5-steroid, [[nicotinamide adenine dinucleotide|NADH]], and [[hydrogen ion|H+]].

== Isozymes ==

Humans express two 3-β-HSD [[isozyme]]s, [[HSD3B1]] (type I) and [[HSD3B2]] (type II).<ref name="pmid15632317">{{cite journal | author = Simard J, Ricketts ML, Gingras S, Soucy P, Feltus FA, Melner MH | title = Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family | journal = Endocr. Rev. | volume = 26 | issue = 4 | pages = 525–82 |date=June 2005 | pmid = 15632317 | doi = 10.1210/er.2002-0050 | url = }}</ref> The type I isoenzyme is expressed in placenta and peripheral tissues, whereas the type II 3β-HSD isoenzyme is expressed in the adrenal gland, ovary, and testis.

== Nomenclature ==

The systematic name of this enzyme class is '''3β-hydroxy-Δ5-steroid:NAD+ 3-oxidoreductase'''. Other names in common use include:

* progesterone reductase
* Δ5-3β-hydroxysteroid dehydrogenase
* 3β-hydroxy-5-ene steroid dehydrogenase
* 3β-hydroxy steroid dehydrogenase/isomerase
* 3β-hydroxy-Δ5-C27-steroid dehydrogenase/isomerase
* 3β-hydroxy-Δ5-C27-steroid oxidoreductase
* 3β-hydroxy-5-ene-steroid oxidoreductase
* steroid-Δ5-3β-ol dehydrogenase
* 3β-HSDH
* 5-ene-3β-hydroxysteroid dehydrogenase
* 3β-hydroxy-5-ene-steroid dehydrogenase

== Inhibitors ==

3-β-HSD is inhibited by [[trilostane]].<ref name="pmid8809191">{{cite journal | author = Cooke GM | title = Differential effects of trilostane and cyanoketone on the 3 beta-hydroxysteroid dehydrogenase-isomerase reactions in androgen and 16-androstene biosynthetic pathways in the pig testis | journal = J. Steroid Biochem. Mol. Biol. | volume = 58 | issue = 1 | pages = 95–101 |date=April 1996 | pmid = 8809191 |doi = 10.1016/0960-0760(96)00002-7| url = }}</ref>

== Biosynthetic pathway ==
{{Gallery
|title=
|footer=
|width=300
|lines=3
|File:Steroidogenesis.svg|Human [[steroidogenesis]], showing reactions of 3β-HSD near-left in green box.
|Image:Corticosteroid-biosynthetic-pathway-rat.png| Corticosteroid biosynthetic pathway in the rat, showing reaction catalyzed by 3β-HSD (second arrow from the top).
}}

==Clinical significance==
A deficiency in the type II form through mutations in HSD3B2 is responsible for a rare form of [[congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase deficiency|congenital adrenal hyperplasia]].<ref name="pmid1363812">{{cite journal | author = Rhéaume E, Simard J, Morel Y, Mebarki F, Zachmann M, Forest MG, New MI, Labrie F | title = Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene | journal = Nat. Genet. | volume = 1 | issue = 4 | pages = 239–45 |date=July 1992 | pmid = 1363812 | doi = 10.1038/ng0792-239 | url = }}</ref> No human condition has yet been linked to a deficiency in the type I enzyme. Its importance in placental progesterone production expression suggests that such a mutation would be embryonically lethal.

== See also ==
* [[3α-Hydroxysteroid dehydrogenase]] (3α-HSD)

==References==
{{reflist|2}}

==Further reading==
{{refbegin | 2}}

* {{cite journal | author = Cheatum SG, Watten JC | year = 1966 | title = Purification and properties of 3-beta-hydroxysteroid dehydrogenase and delta-5-3-ketosteroid isomerase from bovine corpora lutea | journal = Biochim. Biophys. Acta. | volume = 122 | pages = 1–13 | pmid = 4226148 | issue = 1 }}
* {{cite journal | author = Koritz SB | year = 1964 | title = The conversion of prepnenolone to progesterone by small particle from rat adrenal | journal = Biochemistry | volume = 3 | pages = 1098–1102 | doi = 10.1021/bi00896a015 | pmid=14220672 | issue = 8}}
* {{cite journal | author = Neville AM, Orr, JC and Engel LL | year = 1968 | title = Delta5-3beta-Hydroxy steroid dehydrogenase activities of bovine adrenal cortex | journal = Biochem. J. | volume = 107 | pages = 20 }}
{{refend}}

{{Alcohol oxidoreductases}}
{{Steroid metabolism enymes}}

[[Category:EC 1.1.1]]
[[Category:NADH-dependent enzymes]]
[[Category:Enzymes of unknown structure]]

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