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MetaCyc Enzyme: 3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1

Gene: HSD3B1 Accession Number: HS08829 (MetaCyc)

Synonyms: 3BH, HSDB3A, 3-beta-HSD I, steroid delta isomerase, Delta-5-3-ketosteroid isomerase, Progesterone reductase, Trophoblast antigen FDO161G, 3-beta-hydroxy-delta(5)-steroid dehydrogenase

Species: Homo sapiens

Subunit composition of 3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1 = [HSD3B1]2
         3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1 = HSD3B1

Summary:
The 3β-hydroxysteroid dehydrogenases are membrane bound enzymes present in mitochondria and endoplasmic reticulum that are critical for the biosynthesis of all steroid hormones. They are multi-functional enzymes catalyzing the oxidative conversion of delta 5-3 hydroxy steroids to the active delta 4-3 keto configuration . This conversion is carried out in two separate, sequential reactions: first the dehydrogenation of the 3β-hydroxy steroid requiring NAD+ and producing a 3-keto intermediate and NADH; then the reduced coenzyme remains attached to the enzyme and activates the isomerization of the delta-5 steroid [Thomas95].

The substrates include pregnenolone, 17α-hydroxypregnenolone, and dehydroepiandrosterone (DHEA). HSD3β1 and HSD3β2 are distinct genes which encode highly homologous proteins that act on all substrates equally, but differ in expression patterns [Lachance90]. HSD3β1 is expressed in placenta, skin and mammary gland; HSD3β2 is expressed in adrenal gland, testis and ovaries [Lachance91, Rheaume91].

Locations: endoplasmic reticulum, membrane, mitochondrion

Map Position: [118,887,712 -> 118,895,538]

Unification Links: ArrayExpress:P14060 , Ensembl:ENSG00000175511 , Entrez-gene:3283 , Entrez-Nucleotide:BC031999 , Entrez-Nucleotide:M27137 , Entrez-Nucleotide:M35493 , Entrez-Nucleotide:M38180 , Entrez-Nucleotide:M63397 , Entrez-Nucleotide:S45679 , Entrez-Nucleotide:X53321 , Entrez-Nucleotide:X55997 , Entrez:AAA36001 , Entrez:AAA36015 , Entrez:AAA51538 , Entrez:AAA51662 , Entrez:AAA51831 , Entrez:AAB23543 , Entrez:AAH31999 , Entrez:CAA37408 , Entrez:CAA39469 , GeneCards:HSD3B1 , OMIM:109715 , PhosphoSite:P14060 , PhylomeDB:P14060 , Pride:P14060 , Protein Model Portal:P14060 , RefSeq:NM_000862 , RefSeq:NP_000853 , SMR:P14060 , String:9606.ENSP00000358421 , UCSC Human Genome:NM_000862 , UniGene:38586 , UniProt:P14060

Relationship Links: InterPro:IN-FAMILY:IPR002225 , InterPro:IN-FAMILY:IPR016040 , Pfam:IN-FAMILY:PF01073

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

GO Terms:

Biological Process: GO:0006694 - steroid biosynthetic process
GO:0006700 - C21-steroid hormone biosynthetic process
Molecular Function: GO:0003854 - 3-beta-hydroxy-delta5-steroid dehydrogenase activity
GO:0004769 - steroid delta-isomerase activity
GO:0016491 - oxidoreductase activity
GO:0016853 - isomerase activity
Cellular Component: GO:0005739 - mitochondrion
GO:0005783 - endoplasmic reticulum
GO:0016021 - integral component of membrane

Credits:
Created 30-Aug-2010 by Trupp M , SRI International


Enzymatic reaction of: androstenedione isomerase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

5-androstene-3,17-dione <=> androst-4-ene-3,17-dione

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , androgen biosynthesis


Enzymatic reaction of: Steroid Delta-isomerase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

Synonyms: DELTA-5-3-KETOSTEROID ISOMERASE

EC Number: 5.3.3.1

a 3-oxo-δ5-steroid <=> a 3-oxo-Δ4-steroid

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.

Citations: [Thomas02, Rosmond02, Pang02, Luu89, Lachance90, Lorence90, Lorence90a, Morrison91, Nickson91, Russell91a, Dumont92]


Enzymatic reaction of: steroid Delta-isomerase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

Synonyms: 3-β-hydroxy-5-ene steroid dehydrogenase

EC Number: 1.1.1.145

a 3β-hydroxy-δ5-steroid + NAD+ <=> a 3-oxo-δ5-steroid + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.


Enzymatic reaction of: Steroid Delta-isomerase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

EC Number: 1.1.1.210

5-α-androstan-3β,17β-diol + NADP+ <=> 5-α-dihydrotestosterone + NADPH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.


Enzymatic reaction of: DHA dehydrogenase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

EC Number: 1.1.1.145

dehydroepiandrosterone + NAD+ <=> 5-androstene-3,17-dione + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , androgen biosynthesis


Enzymatic reaction of: 17-hydroxypregnenolone dehydrogenase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

EC Number: 1.1.1.145

17-α-hydroxypregnenolone + NAD+ <=> pregn-5-ene-3,20-dione-17-ol + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.


Enzymatic reaction of: 17-hydroxyprogesterone isomerase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

EC Number: 5.3.3.1

pregn-5-ene-3,20-dione-17-ol <=> 17-α-hydroxyprogesterone

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

Reversibility of this reaction is unspecified.


Enzymatic reaction of: pregnenolone 3-dehydrogenase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

EC Number: 1.1.1.145

pregnenolone + NAD+ <=> pregn-5-ene-3,20-dione + NADH + H+

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , progesterone biosynthesis


Enzymatic reaction of: progesterone isomerase (3 β-hydroxysteroid dehydrogenase/ Δ 5-->4-isomerase type 1)

EC Number: 5.3.3.1

pregn-5-ene-3,20-dione <=> progesterone

The reaction direction shown, that is, A + B ↔ C + D versus C + D ↔ A + B, is in accordance with the Enzyme Commission system.

The reaction is favored in the direction shown.

In Pathways: superpathway of steroid hormone biosynthesis , progesterone biosynthesis

Exons/Introns:

Schematic showing introns, exons and/or isoforms of HSD3B1


References

Dumont92: Dumont M, Luu-The V, Dupont E, Pelletier G, Labrie F (1992). "Characterization, expression, and immunohistochemical localization of 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase in human skin." J Invest Dermatol 99(4);415-21. PMID: 1401999

Lachance90: Lachance Y, Luu-The V, Labrie C, Simard J, Dumont M, de Launoit Y, Guerin S, Leblanc G, Labrie F (1990). "Characterization of human 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase gene and its expression in mammalian cells." J Biol Chem 265(33);20469-75. PMID: 2243100

Lachance91: Lachance Y, Luu-The V, Verreault H, Dumont M, Rheaume E, Leblanc G, Labrie F (1991). "Structure of the human type II 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4 isomerase (3 beta-HSD) gene: adrenal and gonadal specificity." DNA Cell Biol 10(10);701-11. PMID: 1741954

Lorence90: Lorence MC, Murry BA, Trant JM, Mason JI (1990). "Human 3 beta-hydroxysteroid dehydrogenase/delta 5----4isomerase from placenta: expression in nonsteroidogenic cells of a protein that catalyzes the dehydrogenation/isomerization of C21 and C19 steroids." Endocrinology 126(5);2493-8. PMID: 2139411

Lorence90a: Lorence MC, Corbin CJ, Kamimura N, Mahendroo MS, Mason JI (1990). "Structural analysis of the gene encoding human 3 beta-hydroxysteroid dehydrogenase/delta 5----4-isomerase." Mol Endocrinol 4(12);1850-5. PMID: 2082186

Luu89: Luu The V, Lachance Y, Labrie C, Leblanc G, Thomas JL, Strickler RC, Labrie F (1989). "Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase." Mol Endocrinol 3(8);1310-2. PMID: 2779585

Morrison91: Morrison N, Nickson DA, McBride MW, Mueller UW, Boyd E, Sutcliffe RG (1991). "Regional chromosomal assignment of human 3-beta-hydroxy-5-ene steroid dehydrogenase to 1p13.1 by non-isotopic in situ hybridisation." Hum Genet 87(2);223-5. PMID: 2066113

Nickson91: Nickson DA, McBride MW, Zeinali S, Hawes CS, Petropoulos A, Mueller UW, Sutcliffe RG (1991). "Molecular cloning and expression of human trophoblast antigen FDO161G and its identification as 3 beta-hydroxy-5-ene steroid dehydrogenase." J Reprod Fertil 93(1);149-56. PMID: 1920284

Pang02: Pang S, Wang W, Rich B, David R, Chang YT, Carbunaru G, Myers SE, Howie AF, Smillie KJ, Mason JI (2002). "A novel nonstop mutation in the stop codon and a novel missense mutation in the type II 3beta-hydroxysteroid dehydrogenase (3beta-HSD) gene causing, respectively, nonclassic and classic 3beta-HSD deficiency congenital adrenal hyperplasia." J Clin Endocrinol Metab 87(6);2556-63. PMID: 12050213

Rheaume91: Rheaume E, Lachance Y, Zhao HF, Breton N, Dumont M, de Launoit Y, Trudel C, Luu-The V, Simard J, Labrie F (1991). "Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase/delta 5-delta 4-isomerase in human adrenals and gonads." Mol Endocrinol 5(8);1147-57. PMID: 1944309

Rosmond02: Rosmond R, Chagnon M, Bouchard C, Bjorntorp P (2002). "Polymorphism in exon 4 of the human 3 beta-hydroxysteroid dehydrogenase type I gene (HSD3B1) and blood pressure." Biochem Biophys Res Commun 293(1);629-32. PMID: 12054649

Russell91a: Russell AJ, Gaffney D, Gardiner MT, Nickson DA, Sutcliffe RG (1991). "Synonymous polymorphism in the coding sequence of human 3-beta hydroxysteroid-5-ene dehydrogenase (HSD)." Nucleic Acids Res 19(5);1172. PMID: 1673569

Thomas02: Thomas JL, Mason JI, Brandt S, Spencer BR, Norris W (2002). "Structure/function relationships responsible for the kinetic differences between human type 1 and type 2 3beta-hydroxysteroid dehydrogenase and for the catalysis of the type 1 activity." J Biol Chem 277(45);42795-801. PMID: 12205101

Thomas89: Thomas JL, Myers RP, Strickler RC (1989). "Human placental 3 beta-hydroxy-5-ene-steroid dehydrogenase and steroid 5----4-ene-isomerase: purification from mitochondria and kinetic profiles, biophysical characterization of the purified mitochondrial and microsomal enzymes." J Steroid Biochem 33(2);209-17. PMID: 2770297

Thomas95: Thomas JL, Frieden C, Nash WE, Strickler RC (1995). "An NADH-induced conformational change that mediates the sequential 3 beta-hydroxysteroid dehydrogenase/isomerase activities is supported by affinity labeling and the time-dependent activation of isomerase." J Biol Chem 270(36);21003-8. PMID: 7673125


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Please cite the following article in publications resulting from the use of MetaCyc: Caspi et al, Nucleic Acids Research 42:D459-D471 2014
Page generated by SRI International Pathway Tools version 19.0 on Fri Mar 27, 2015, BIOCYC13A.