Steroid 11β-hydroxylase

Not to be confused with 11β-Hydroxysteroid dehydrogenase.

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Identifiers
Aliases
External IDs	GeneCards: [1]
Orthologs
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a
Wikidata
View/Edit Human

Steroid 11β-hydroxylase is a steroid hydroxylase found in the zona glomerulosa and zona fasciculata. Named officially the cytochrome P450 11B1, mitochondrial, it is a protein that in humans is encoded by the CYP11B1 gene.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of 11-deoxycortisol to cortisol in the adrenal cortex. Transcript variants encoding different isoforms have been noted for this gene.

It is reversibly inhibited by etomidate and metyrapone.

Function

steroid 11β-monooxygenase
Identifiers
EC number	1.14.15.4
CAS number	9029-66-7
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 / QuickGO
Search PMC articles PubMed articles NCBI proteins

It generates cortisol from 11-deoxycortisol and corticosterone from 11-deoxycorticosterone. Note the extra "–OH" added at the 11 position (near the center, on ring "C"):

• 11-Deoxycortisol
  11-Deoxycortisol
• 
  Cortisol
• 11-Deoxycorticosterone
  11-Deoxycorticosterone
• Error creating thumbnail: File missing
  Corticosterone

Mechanism of action

As a mitochondrial P450 system, P450c11 is dependent on two electron transfer proteins, adrenodoxin reductase and adrenodoxin that transfer 2 electrons from NADPH to the P450 for each monooxygenase reaction catalyzed by the enzyme. In most respects this process of electron transfer appears similar to that of P450scc system that catalyzes cholesterol side chain cleavage. Similar to P450scc the process of electrons transfer is leaky leading to superoxide production. The rate of electron leakage during metabolism depends on the functional groups of the steroid substrate.

Regulation

The expression of the enzyme in adrenocortical cells is regulated by the trophic hormone corticotropin (ACTH).

Clinical significance

A mutation is associated with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.

See also

• Steroidogenic enzyme

Additional images

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Steroidogenesis, showing steroid 11-beta-hydroxylase vertically at right.

• 
  Corticosteroid biosynthetic pathway in rat
• Steroid numbering
  Steroid numbering

Further reading

• Helmberg A (August 1993). "Twin genes and endocrine disease: CYP21 and CYP11B genes". Acta Endocrinol. 129 (2): 97–108. doi:10.1530/acta.0.1290097. PMID 8372604.
• Stowasser M, Gunasekera TG, Gordon RD (December 2001). "Familial varieties of primary aldosteronism". Clin. Exp. Pharmacol. Physiol. 28 (12): 1087–90. doi:10.1046/j.1440-1681.2001.03574.x. PMID 11903322.
• Helmberg A, Ausserer B, Kofler R (November 1992). "Frame shift by insertion of 2 basepairs in codon 394 of CYP11B1 causes congenital adrenal hyperplasia due to steroid 11 beta-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 75 (5): 1278–81. doi:10.1210/jc.75.5.1278. PMID 1430088.
• Pascoe L, Curnow KM, Slutsker L, Connell JM, Speiser PW, New MI, White PC (September 1992). "Glucocorticoid-suppressible hyperaldosteronism results from hybrid genes created by unequal crossovers between CYP11B1 and CYP11B2". Proc. Natl. Acad. Sci. U.S.A. 89 (17): 8327–31. doi:10.1073/pnas.89.17.8327. PMC 49911. PMID 1518866.
• Kawamoto T, Mitsuuchi Y, Toda K, Yokoyama Y, Miyahara K, Miura S, Ohnishi T, Ichikawa Y, Nakao K, Imura H (February 1992). "Role of steroid 11 beta-hydroxylase and steroid 18-hydroxylase in the biosynthesis of glucocorticoids and mineralocorticoids in humans". Proc. Natl. Acad. Sci. U.S.A. 89 (4): 1458–62. doi:10.1073/pnas.89.4.1458. PMC 48470. PMID 1741400.
• White PC, Dupont J, New MI, Leiberman E, Hochberg Z, Rösler A (May 1991). "A mutation in CYP11B1 (Arg-448----His) associated with steroid 11 beta-hydroxylase deficiency in Jews of Moroccan origin". J. Clin. Invest. 87 (5): 1664–7. doi:10.1172/JCI115182. PMC 295260. PMID 2022736.
• Kawamoto T, Mitsuuchi Y, Toda K, Miyahara K, Yokoyama Y, Nakao K, Hosoda K, Yamamoto Y, Imura H, Shizuta Y (September 1990). "Cloning of cDNA and genomic DNA for human cytochrome P-45011 beta". FEBS Lett. 269 (2): 345–9. doi:10.1016/0014-5793(90)81190-Y. PMID 2401360.
• Mornet E, Dupont J, Vitek A, White PC (December 1989). "Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta)". J. Biol. Chem. 264 (35): 20961–7. PMID 2592361.
• Chua SC, Szabo P, Vitek A, Grzeschik KH, John M, White PC (October 1987). "Cloning of cDNA encoding steroid 11 beta-hydroxylase (P450c11)". Proc. Natl. Acad. Sci. U.S.A. 84 (20): 7193–7. doi:10.1073/pnas.84.20.7193. PMC 299256. PMID 3499608.
• Naiki Y, Kawamoto T, Mitsuuchi Y, Miyahara K, Toda K, Orii T, Imura H, Shizuta Y (December 1993). "A nonsense mutation (TGG [Trp116]-->TAG [Stop]) in CYP11B1 causes steroid 11 beta-hydroxylase deficiency". J. Clin. Endocrinol. Metab. 77 (6): 1677–82. doi:10.1210/jc.77.6.1677. PMID 7903314.
• Joehrer K, Geley S, Strasser-Wozak EM, Azziz R, Wollmann HA, Schmitt K, Kofler R, White PC (October 1997). "CYP11B1 mutations causing non-classic adrenal hyperplasia due to 11 beta-hydroxylase deficiency". Hum. Mol. Genet. 6 (11): 1829–34. doi:10.1093/hmg/6.11.1829. PMID 9302260.
• Cargill M, Altshuler D, Ireland J, Sklar P, Ardlie K, Patil N, Shaw N, Lane CR, Lim EP, Kalyanaraman N, Nemesh J, Ziaugra L, Friedland L, Rolfe A, Warrington J, Lipshutz R, Daley GQ, Lander ES (July 1999). "Characterization of single-nucleotide polymorphisms in coding regions of human genes". Nat. Genet. 22 (3): 231–8. doi:10.1038/10290. PMID 10391209.
• Halushka MK, Fan JB, Bentley K, Hsie L, Shen N, Weder A, Cooper R, Lipshutz R, Chakravarti A (July 1999). "Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis". Nat. Genet. 22 (3): 239–47. doi:10.1038/10297. PMID 10391210.
• Cao PR, Bernhardt R (June 1999). "Interaction of CYP11B1 (cytochrome P-45011 beta) with CYP11A1 (cytochrome P-450scc) in COS-1 cells". Eur. J. Biochem. 262 (3): 720–6. doi:10.1046/j.1432-1327.1999.00414.x. PMID 10411633.
• Loidi L, Quinteiro C, Barros F, Domínguez F, Barreiro J, Pombo M (December 1999). "The C494F variant in the CYP11B1 gene is a sequence polymorphism in the Spanish population". J. Clin. Endocrinol. Metab. 84 (12): 4749. doi:10.1210/jc.84.12.4749. PMID 10599751.
• Chabre O, Portrat-Doyen S, Chaffanjon P, Vivier J, Liakos P, Labat-Moleur F, Chambaz E, Morel Y, Defaye G (November 2000). "Bilateral laparoscopic adrenalectomy for congenital adrenal hyperplasia with severe hypertension, resulting from two novel mutations in splice donor sites of CYP11B1". J. Clin. Endocrinol. Metab. 85 (11): 4060–8. doi:10.1210/jc.85.11.4060. PMID 11095433.
• Fisher A, Friel EC, Bernhardt R, Gomez-Sanchez C, Connell JM, Fraser R, Davies E (September 2001). "Effects of 18-hydroxylated steroids on corticosteroid production by human aldosterone synthase and 11beta-hydroxylase". J. Clin. Endocrinol. Metab. 86 (9): 4326–9. doi:10.1210/jc.86.9.4326. PMID 11549669.
• Hampf M, Dao NT, Hoan NT, Bernhardt R (September 2001). "Unequal crossing-over between aldosterone synthase and 11beta-hydroxylase genes causes congenital adrenal hyperplasia". J. Clin. Endocrinol. Metab. 86 (9): 4445–52. doi:10.1210/jc.86.9.4445. PMID 11549691.

External links

• Steroid+11-beta-hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH)