|Cytochrome P450, family 11, subfamily B, polypeptide 1|
|Symbols||; CPN1; CYP11B; FHI; P450C11|
|External IDs||ChEMBL: GeneCards:|
|RNA expression pattern|
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.
- Function 1
- Mechanism of action 2
- Regulation 3
- Clinical significance 4
- Additional images 5
- References 6
- Further reading 7
- External links 8
|PDB structures||RCSB PDB PDBe PDBsum|
|Gene Ontology||AmiGO / EGO|
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.
The expression of the enzyme in adrenocortical cells is regulated by the trophic hormone corticotropin (ACTH.
A mutation is associated with congenital adrenal hyperplasia due to 11β-hydroxylase deficiency.
Corticosteroid biosynthetic pathway in rat
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- "Entrez Gene: CYP11B1 cytochrome P450, family 11, subfamily B, polypeptide 1".
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- 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.
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- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Steroid 11-beta-hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH)