3 β- hydroxysteroid dehydrogenase
| 3 β- hydroxysteroid dehydrogenase | ||
|---|---|---|
| Mass / length primary structure | 371/372/369 amino acids | |
| Secondary to quaternary structure | single-pass membrane protein (ER, Mit.) | |
| Isoforms | NP_000853, NP_000189, NP_079469 | |
| Identifier | ||
| Gene name (s) | HSD3B1 , HSD3B2 , HSD3B7 | |
| External IDs | ||
| Enzyme Classifications | ||
| EC, category | 1.1.1.145 , oxidoreductase | |
| Response type | Dehydration | |
| Substrate | Pregnenolone + NAD + | |
| Products | Pregn-5-ene-3,20-dione + NADH / H + | |
| EC, category | 5.3.3.1 , isomerase | |
| Response type | Rearrangement | |
| Substrate | Pregn-5-en-3,20-dione | |
| Products | progesterone | |
| Occurrence | ||
| Parent taxon | multicellular animals , protozoa | |
3 β -hydroxysteroid dehydrogenases (3β-HSD) are enzymes which in steroids 3 β - hydroxy group to the ketone oxidize and at the same time the rearrangement of the double bond of the 5 in the 4-position catalyze . This reaction is required in vertebrates in the biosynthesis of progesterone from pregnenolone , as well as in the conversion of dehydroepiandrosterone to androstenedione or from 17 α -hydroxypregnenolone to 17 α -hydroxyprogesterone .
3 β- HSD are transmembrane proteins and localize to the endoplasmic reticulum and to the mitochondria . In humans, three paralogous isoforms are known which are expressed in different tissue types : 3 β -HSD I mainly in the mammary glands , placenta and skin ; 3 β- HSD II mainly in the adrenal glands , testes and ovaries . Mutations in HSD3B2 - gene are responsible for a Adrenogenital syndrome type 2 ( CAH by 3-beta-hydroxysteroid dehydrogenase deficiency ). The third human enzyme of this protein family 3 β -HSD type 7, an enzyme of bile acid formation from cholesterol.
Catalyzed reactions
+ NAD + ⇔⇔ 
+ NAD H / H +
Pregnenolone is converted to progesterone. A dehydration to the ketone and a rearrangement of the double bond take place one after the other . Another reaction is the conversion of DHEA to androstenedione .
Structure reference
Structure model of HSD3B1: see fourth web link; out
Individual evidence
- ↑ Homologues at inParanoid
- ↑ a b Welzel M, Wüstemann N, Sîmić-Schleicher G, et al. : Carboxyl Terminal Mutations in 3β-Hydroxysteroid Dehydrogenase Type II Cause Severe Salt-Wasting Congenital Adrenal Hyperplasia . In: J. Clin. Endocrine. Metabol. . 93, August, pp. 1418-1425.
- ↑ UniProt P26439 , UniProt P14060
- ↑ Simard J, Ricketts ML, Gingras S et al. : Molecular Biology of the 3β-Hydroxysteroid Dehydrogenase / Δ5-Δ4 Isomerase Gene Family . In: Endocrine Rev. . 26, 2005, pp. 525-582. doi : 10.1210 / er.2002-0050 . PMID 15632317 .
- ↑ Pletnev VZ, Thomas JL, Rhaney FL, et al. : Rational proteomics V: structure-based mutagenesis has revealed key residues responsible for substrate recognition and catalysis by the dehydrogenase and isomerase activities in human 3beta-hydroxysteroid dehydrogenase / isomerase type 1 . In: J. Steroid Biochem. Mol. Biol . 101, No. 1, September 2006, pp. 50-60. doi : 10.1016 / j.jsbmb.2006.06.004 . PMID 16889958 . PMC 1971842 (free full text).
- ↑ Thomas JL, et al. : Structure / Function Relationships Responsible for Coenzyme Specificity and the Isomerase Activity of Human Type 1 3β-Hydroxysteroid Dehydrogenase / Isomerase . In: J.Biol.Chem. . 278, 2003, pp. 35483-35490. PMID 12832414 .
Web links
- Jassal / reactome: Pregnenolone is dehydrogenated to form pregn-5-ene-3,20-dione
- Jassal / reactome: Pregn-5-ene-3,20-dione isomerizes to progesterone
- Jassal / reactome: DHA isomerizes to 4-Androstene3,17-dione
- Structure reference
