3-beta-HSD
| 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 | ||||||||
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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 | |
| 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 | |
| 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.
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
Reaction
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
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
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.[4]
Biosynthetic pathway
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Clinical significance
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
- 3α-Hydroxysteroid dehydrogenase (3α-HSD)
References
- ↑ 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
- 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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