| 3β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase |
| Identifiers |
| EC number |
1.1.1.145 |
| CAS number |
9044-85-3 |
| Databases |
| IntEnz |
IntEnz view |
| BRENDA |
BRENDA entry |
| ExPASy |
NiceZyme view |
| KEGG |
KEGG entry |
| MetaCyc |
metabolic pathway |
| PRIAM |
profile |
| PDB structures |
RCSB PDB PDBe PDBsum |
| Gene Ontology |
AmiGO / EGO |
| Search |
| PMC |
articles |
| PubMed |
articles |
| NCBI |
proteins |
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hydroxy-Δ-5-steroid dehydrogenase,
3β- and steroid Δ-isomerase 1 |
| Identifiers |
| Symbol |
HSD3B1 |
| Alt. symbols |
HSDB3, HSD3B |
| Entrez |
3283 |
| HUGO |
5217 |
| OMIM |
109715 |
| RefSeq |
NM_000862 |
| UniProt |
P14060 |
| Other data |
| EC number |
1.1.1.145 |
| Locus |
Chr. 1 p13-p11 |
hydroxy-Δ-5-steroid dehydrogenase,
3β- and steroid Δ-isomerase 2 |
| Identifiers |
| Symbol |
HSD3B2 |
| Entrez |
3284 |
| HUGO |
5218 |
| OMIM |
613890 |
| RefSeq |
NM_000198 |
| UniProt |
P26439 |
| Other data |
| EC number |
1.1.1.145 |
| Locus |
Chr. 1 p13.1 |
3-β-HSD (or 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase) (EC 1.1.1.145) is an enzyme that 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.[1] In humans, there are two 3-β-HSD isozymes encoded by the HSD3B1 and HSD3B2 genes, respectively.
It is also known as delta 5-delta 4-isomerase, which catalyzes the oxidative conversion of delta 5-3 beta- hydroxysteroids to the delta 4-3-keto configuration and is, therefore, essential for the biosynthesis of all classes of hormonal steroids, namely progesterone, glucocorticoids, mineralocorticoids, androgens, and estrogens.[2] 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
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Contents
- 1 Reaction
- 2 Isozymes
- 3 Nomenclature
- 4 Inhibitors
- 5 Biosynthetic pathway
- 6 Clinical significance
- 7 See also
- 8 References
- 9 Further reading
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Reaction[edit]
3-β-HSD belongs to the family of oxidoreductases, 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 catalyzes the chemical reaction:
- a 3β-hydroxy-Δ5-steroid + NAD+ a 3-oxo-Δ5-steroid + NADH + H+
Thus, the two substrates of this enzyme are 3β-hydroxy-Δ5-steroid and NAD+, whereas its 3 products are 3-oxo-Δ5-steroid, NADH, and H+.
Isozymes[edit]
Humans express two 3-β-HSD isozymes, HSD3B1 (type I) and HSD3B2 (type II).[3] 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[edit]
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[edit]
3-β-HSD is inhibited by trilostane.[4]
Biosynthetic pathway[edit]
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Human steroidogenesis, showing reactions of 3β-HSD near-left in green box.
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Corticosteroid biosynthetic pathway in the rat, showing reaction catalyzed by 3β-HSD (second arrow from the top).
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Clinical significance[edit]
A deficiency in the type II form through mutations in HSD3B2 is responsible for a rare form of congenital adrenal hyperplasia.[5] 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[edit]
- 3α-Hydroxysteroid dehydrogenase (3α-HSD)
References[edit]
- ^ Cravioto MD, Ulloa-Aguirre A, Bermudez JA, Herrera J, Lisker R, Mendez JP, Perez-Palacios G (August 1986). "A new inherited variant of the 3 beta-hydroxysteroid dehydrogenase-isomerase deficiency syndrome: evidence for the existence of two isoenzymes". J. Clin. Endocrinol. Metab. 63 (2): 360–7. doi:10.1210/jcem-63-2-360. PMID 3088022.
- ^ Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guérin S, Leblanc G, Labrie F (February 1992). "Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells". J. Biol. Chem. 267 (5): 3551. PMID 1737804.
- ^ Simard J, Ricketts ML, Gingras S, Soucy P, Feltus FA, Melner MH (June 2005). "Molecular biology of the 3beta-hydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family". Endocr. Rev. 26 (4): 525–82. doi:10.1210/er.2002-0050. PMID 15632317.
- ^ Cooke GM (April 1996). "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". J. Steroid Biochem. Mol. Biol. 58 (1): 95–101. doi:10.1016/0960-0760(96)00002-7. PMID 8809191.
- ^ Rhéaume E, Simard J, Morel Y, Mebarki F, Zachmann M, Forest MG, New MI, Labrie F (July 1992). "Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene". Nat. Genet. 1 (4): 239–45. doi:10.1038/ng0792-239. PMID 1363812.
Further reading[edit]
- Cheatum SG, Watten JC (1966). "Purification and properties of 3-beta-hydroxysteroid dehydrogenase and delta-5-3-ketosteroid isomerase from bovine corpora lutea". Biochim. Biophys. Acta. 122 (1): 1–13. PMID 4226148.
- Koritz SB (1964). "The conversion of prepnenolone to progesterone by small particle from rat adrenal". Biochemistry 3 (8): 1098–1102. doi:10.1021/bi00896a015. PMID 14220672.
- Neville AM, Orr, JC and Engel LL (1968). "Delta5-3beta-Hydroxy steroid dehydrogenase activities of bovine adrenal cortex". Biochem. J. 107: 20.
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Oxidoreductases: alcohol oxidoreductases (EC 1.1)
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| 1.1.1: NAD/NADP acceptor |
- 3-hydroxyacyl-CoA dehydrogenase
- 3-hydroxybutyryl-CoA dehydrogenase
- Alcohol dehydrogenase
- Aldo-keto reductase
- 1A1
- 1B1
- 1B10
- 1C1
- 1C3
- 1C4
- 7A2
- Aldose reductase
- Beta-Ketoacyl ACP reductase
- Carbohydrate dehydrogenases
- Carnitine dehydrogenase
- D-malate dehydrogenase (decarboxylating)
- DXP reductoisomerase
- Glucose-6-phosphate dehydrogenase
- Glycerol-3-phosphate dehydrogenase
- HMG-CoA reductase
- IMP dehydrogenase
- Isocitrate dehydrogenase
- Lactate dehydrogenase
- L-threonine dehydrogenase
- L-xylulose reductase
- Malate dehydrogenase
- Malate dehydrogenase (decarboxylating)
- Malate dehydrogenase (NADP+)
- Malate dehydrogenase (oxaloacetate-decarboxylating)
- Malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+)
- Phosphogluconate dehydrogenase
- Sorbitol dehydrogenase
- Hydroxysteroid dehydrogenase: 3 Beta
- 11 Beta
- 17 Beta
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| 1.1.2: cytochrome acceptor |
- D-lactate dehydrogenase (cytochrome)
- D-lactate dehydrogenase (cytochrome c-553)
- Mannitol dehydrogenase (cytochrome)
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| 1.1.3: oxygen acceptor |
- Glucose oxidase
- L-gulonolactone oxidase
- Xanthine oxidase
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| 1.1.4: disulfide as acceptor |
- Vitamin K epoxide reductase
- Vitamin-K-epoxide reductase (warfarin-insensitive)
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| 1.1.5: quinone/similar acceptor |
- Malate dehydrogenase (quinone)
- Quinoprotein glucose dehydrogenase
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| 1.1.99: other acceptors |
- Choline dehydrogenase
- L2HGDH
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- B
- enzm
- 1.1
- 2
- 3
- 4
- 5
- 6
- 7
- 8
- 10
- 11
- 13
- 14
- 15-18
- 2.1
- 3.1
- 4.1
- 5.1
- 6.1-3
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Metabolism: lipid metabolism – ketones/cholesterol synthesis enzymes/steroid metabolism
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| Mevalonate pathway |
| To HMG-CoA |
- Acetyl-Coenzyme A acetyltransferase
- HMG-CoA synthase (regulated step)
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| Ketogenesis |
- HMG-CoA lyase
- 3-hydroxybutyrate dehydrogenase
- Thiophorase
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| To Mevalonic acid |
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| To DMAPP |
- Mevalonate kinase
- Phosphomevalonate kinase
- Pyrophosphomevalonate decarboxylase
- Isopentenyl-diphosphate delta isomerase
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| Geranyl- |
- Dimethylallyltranstransferase
- Geranyl pyrophosphate
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| To cholesterol |
| To lanosterol |
- Farnesyl-diphosphate farnesyltransferase
- Squalene monooxygenase
- Lanosterol synthase
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| 7-Dehydrocholesterol path |
- Lanosterol 14α-demethylase
- Sterol-C5-desaturase-like
- 7-Dehydrocholesterol reductase
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| Desmosterol path |
- 24-dehydrocholesterol reductase
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| To Bile acids |
- Cholesterol 7α-hydroxylase
- Sterol 27-hydroxylase
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| Steroidogenesis |
| To pregnenolone |
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| To corticosteroids |
- aldosterone: 18-hydroxylase
- cortisol/cortisone: 17α-hydroxylase
- 11β dehydrogenase
- both: 3β dehydrogenase
- 21α-hydroxylase
- 11β-hydroxylase
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| To sex hormones |
| To androgens |
- 17α-hydroxylase/17,20 lyase
- 3β dehydrogenase
- 17β dehydrogenase
- 5α reductase
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| To estrogens |
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| Other/ungrouped |
- Steroid metabolism: sulfatase
- sulfotransferase
- Steroidogenic acute regulatory protein
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mt, k, c/g/r/p/y/i, f/h/s/l/o/e, a/u, n, m
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k, cgrp/y/i, f/h/s/l/o/e, au, n, m, epon
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m (A16/C10), i (k, c/g/r/p/y/i, f/h/s/o/e, a/u, n, m)
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noco (d)/cong/tumr, sysi/epon
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proc, drug (A10/H1/H2/H3/H5)
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