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
Search PMC articles PubMed articles

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) is an enzyme that catalyses 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

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⁺ $\rightleftharpoons$ 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

Human steroidogenesis, showing reactions of 3β-HSD near-left in green box.   Corticosteroid biosynthetic pathway in the rat, showing reaction catalyzed by 3β-HSD (second arrow from the top).

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

• 3-β(or 20-α)-hydroxysteroid dehydrogenase

References

1. ^ 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. 
2. ^ 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. 
3. ^ 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. 
4. ^ 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. 
5. ^ 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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