| 3β-hydroxysteroid dehydrogenase/Δ-5-4 isomerase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Identifiers | |||||||||
| EC no. | 1.1.1.145 | ||||||||
| CAS no. | 9044-85-3 | ||||||||
| Databases | |||||||||
| IntEnz | IntEnz view | ||||||||
| BRENDA | BRENDA entry | ||||||||
| ExPASy | NiceZyme view | ||||||||
| KEGG | KEGG entry | ||||||||
| MetaCyc | metabolic pathway | ||||||||
| PRIAM | profile | ||||||||
| PDB structures | RCSB PDBPDBePDBsum | ||||||||
| Gene Ontology | AmiGO /QuickGO | ||||||||
| |||||||||
| 3β-Hydroxysteroid dehydrogenase | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | HSD3B | ||||||
| Pfam | PF01073 | ||||||
| InterPro | IPR002225 | ||||||
| Membranome | 245 | ||||||
| |||||||
| hydroxy-Δ-5-steroid dehydrogenase, 3β- and steroid Δ-isomerase 1 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | HSD3B1 | ||||||
| Alt. symbols | HSDB3, HSD3B | ||||||
| NCBI gene | 3283 | ||||||
| HGNC | 5217 | ||||||
| OMIM | 109715 | ||||||
| RefSeq | NM_000862 | ||||||
| UniProt | P14060 | ||||||
| Other data | |||||||
| EC number | 1.1.1.145 | ||||||
| Locus | Chr. 1p13-p11 | ||||||
| |||||||
| hydroxy-Δ-5-steroid dehydrogenase, 3β- and steroid Δ-isomerase 2 | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | HSD3B2 | ||||||
| NCBI gene | 3284 | ||||||
| HGNC | 5218 | ||||||
| OMIM | 613890 | ||||||
| RefSeq | NM_000198 | ||||||
| UniProt | P26439 | ||||||
| Other data | |||||||
| EC number | 1.1.1.145 | ||||||
| Locus | Chr. 1p13.1 | ||||||
| |||||||
3β-Hydroxysteroid dehydrogenase/Δ5-4 isomerase (3β-HSD) (EC1.1.1.145) is anenzyme thatcatalyzes thebiosynthesis of thesteroidprogesterone frompregnenolone,17α-hydroxyprogesterone from17α-hydroxypregnenolone, andandrostenedione fromdehydroepiandrosterone (DHEA) in theadrenal gland. It is the only enzyme in the adrenal pathway ofcorticosteroid synthesis that is not a member of thecytochrome P450 family.[1] It is also present in other steroid-producing tissues, including theovary,testis andplacenta. In humans, there are two 3β-HSDisozymes encoded by theHSD3B1 andHSD3B2genes.
3β-HSD is also known as delta Δ5-4-isomerase, which catalyzes the oxidative conversion of Δ5-3β-hydroxysteroids to the Δ4-3-keto configuration and is, therefore, essential for thebiosynthesis of all classes ofhormonalsteroids, namelyprogesterone,glucocorticoids,mineralocorticoids,androgens, andestrogens.[2]
The 3β-HSD complex is responsible for the conversion of:
3β-HSD belongs to the family ofoxidoreductases, to be specific, those acting on the CH-OH group with NAD+ or NADP+ as acceptor. This enzyme participates in C21-steroid hormone metabolism and androgen and estrogen metabolism.
3β-HSD catalysis|catalyzes thechemical reaction:
The twosubstrates of this enzyme are 3β-hydroxy-Δ5-steroid andNAD+. Itsproducts are 3-oxo-Δ5-steroid,NADH, andH+.
An example with oxidation and simultaneous double bondisomerism is the conversion of pregnenolone to progesterone:[3]
Humans express two 3β-HSD isozymes,HSD3B1 (type I) andHSD3B2 (type II).[4] 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.[citation needed]
Thesystematic name of this enzyme class is3β-hydroxy-Δ5-steroid:NAD+ 3-oxidoreductase. Other names in common use include:
3β-HSD is potently inhibited byazastene,cyanoketone,epostane, andtrilostane.[5]Medroxyprogesterone acetate andmedrogestone are weak inhibitors of 3β-HSD which may substantially inhibit it at high dosages.[citation needed]
A deficiency in the type II form through mutations in HSD3B2 is responsible for arare form of congenital adrenal hyperplasia.[6] 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.[citation needed]
The fetal adrenal cortex lacks expression of the enzyme early on, thusmineralocorticoids (e.g.aldosterone) andglucocorticoids (e.g.cortisol) cannot be synthesized. This is significant because cortisol inducestype II pneumocytes of thelungs to synthesize and secretepulmonary surfactant; without pulmonary surfactant to reduce thealveolarsurface tension,premature neonates may die ofneonatal respiratory distress syndrome. If delivery is unavoidable (e.g. because ofplacental abruption, orpre-eclampsia/HELLP syndrome), then glucocorticoids (e.g. cortisol) can be administered.[citation needed]
