Steroid 11-beta-hydroxylase

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Cytochrome P450, family 11, subfamily B, polypeptide 1
Identifiers
Symbols CYP11B1 ; CPN1; CYP11B; FHI; P450C11
External IDs OMIM610613 MGI88584 HomoloGene128035 ChEMBL: 1908 GeneCards: CYP11B1 Gene
EC number 1.14.15.4
RNA expression pattern
PBB GE CYP11B1 214610 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1584 13072
Ensembl ENSG00000160882 ENSMUSG00000022589
UniProt P15538 P15539
RefSeq (mRNA) NM_000497 NM_009991
RefSeq (protein) NP_000488 NP_034121
Location (UCSC) Chr 8:
143.95 – 143.96 Mb
Chr 15:
74.85 – 74.86 Mb
PubMed search [1] [2]
Not to be confused with 11-Beta hydroxysteroid dehydrogenase.

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.[1][2]

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.[2]

It is reversibly inhibited by etomidate [3][4] and metyrapone.

Function[edit]

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 / EGO

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"):

Mechanism of action[edit]

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.[5] 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.[6]

Regulation[edit]

The expression of the enzyme in adrenocortical cells is regulated by the trophic hormone corticotropin (ACTH.[7]

Clinical significance[edit]

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

Additional images[edit]

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

References[edit]

  1. ^ Lifton RP, Dluhy RG, Powers M, Rich GM, Gutkin M, Fallo F, Gill JR Jr, Feld L, Ganguly A (Jun 1993). "Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase". Nat Genet 2 (1): 66–74. doi:10.1038/ng0992-66. PMID 1303253. 
  2. ^ a b "Entrez Gene: CYP11B1 cytochrome P450, family 11, subfamily B, polypeptide 1". 
  3. ^ Dörr HG, Kuhnle U, Holthausen H, Bidlingmaier F, Knorr D (November 1984). "Etomidate: a selective adrenocortical 11 beta-hydroxylase inhibitor". Klinische Wochenschrift 62 (21): 1011–3. doi:10.1007/bf01711722. PMID 6096625. 
  4. ^ Carol L. Lake (7 December 2004). Pediatric Cardiac Anesthesia. Lippincott Williams & Wilkins. p. 68. ISBN 978-0-7817-5175-9. Retrieved 30 April 2012. 
  5. ^ Hanukoglu I, Privalle CT, Jefcoate CR (May 1981). "Mechanisms of ionic activation of adrenal mitochondrial cytochromes P-450scc and P-45011 beta". J. Biol. Chem. 256 (9): 4329–35. PMID 6783659. 
  6. ^ Rapoport R, Sklan D, Hanukoglu I (March 1995). "Electron leakage from the adrenal cortex mitochondrial P450scc and P450c11 systems: NADPH and steroid dependence". Arch. Biochem. Biophys. 317 (2): 412–6. doi:10.1006/abbi.1995.1182. PMID 7893157. 
  7. ^ Hanukoglu I, Feuchtwanger R, Hanukoglu A (November 1990). "Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells". J. Biol. Chem. 265 (33): 20602–8. PMID 2173715. 

Further reading[edit]

External links[edit]