|3β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase|
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
3β- and steroid Δ-isomerase 1
|Alt. symbols||HSDB3, HSD3B|
|Locus||Chr. 1 p13-p11|
3β- and steroid Δ-isomerase 2
|Locus||Chr. 1 p13.1|
3-β-HSD (or 3-β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase) (EC 18.104.22.168) 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. 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. 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
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.
- a 3β-hydroxy-Δ5-steroid + NAD+ a 3-oxo-Δ5-steroid + NADH + H+
Humans express two 3-β-HSD isozymes, HSD3B1 (type I) and HSD3B2 (type II). 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.
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
- 5-ene-3β-hydroxysteroid dehydrogenase
- 3β-hydroxy-5-ene-steroid dehydrogenase
A deficiency in the type II form through mutations in HSD3B2 is responsible for a rare form of congenital adrenal hyperplasia. 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.
- 3α-Hydroxysteroid dehydrogenase (3α-HSD)
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- 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.
- 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.