“Steroid 11β-hydroxylase”的意思、由来-开放百科全书

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]

Function

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

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

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

Clinical significance

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

See also

Additional images

References

1. ^{{cite journal | author = Lifton RP | title = Hereditary hypertension caused by chimaeric gene duplications and ectopic expression of aldosterone synthase | journal = Nat Genet | volume = 2 | issue = 1 | pages = 66–74 |date=Jun 1993 | pmid = 1303253 | pmc = | doi = 10.1038/ng0992-66 |name-list-format=vanc| author2 = Dluhy RG | author3 = Powers M | author4 = Rich GM | author5 = Gutkin M | author6 = Fallo F | author7 = Gill JR Jr | author8 = Feld L | author9 = Ganguly A }}
2. ^¹{{cite web | title = Entrez Gene: CYP11B1 cytochrome P450, family 11, subfamily B, polypeptide 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1584| accessdate = }}
3. ^{{cite journal |vauthors=Dörr HG, Kuhnle U, Holthausen H, Bidlingmaier F, Knorr D | title = Etomidate: a selective adrenocortical 11 beta-hydroxylase inhibitor | journal = Klinische Wochenschrift | volume = 62 | issue = 21 | pages = 1011–3 |date=November 1984 | pmid = 6096625 | doi = 10.1007/bf01711722| url = }}
4. ^{{cite book | author = Carol L. Lake | title = Pediatric Cardiac Anesthesia | url = https://books.google.com/books?id=ymuHmUWuUsAC&pg=PA68 | accessdate = 30 April 2012 | date = 7 December 2004 | publisher = Lippincott Williams & Wilkins | isbn = 978-0-7817-5175-9 | page = 68}}
5. ^{{cite journal |vauthors=Hanukoglu I, Privalle CT, Jefcoate CR | title = Mechanisms of ionic activation of adrenal mitochondrial cytochromes P-450scc and P-45011 beta | journal = J. Biol. Chem. | volume = 256 | issue = 9 | pages = 4329–35 |date=May 1981 | pmid = 6783659 | doi = | url = http://www.jbc.org/content/256/9/4329.full.pdf }}
6. ^{{cite journal |vauthors=Rapoport R, Sklan D, Hanukoglu I | title = Electron leakage from the adrenal cortex mitochondrial P450scc and P450c11 systems: NADPH and steroid dependence | journal = Arch. Biochem. Biophys. | volume = 317 | issue = 2 | pages = 412–6 |date=March 1995 | pmid = 7893157 | doi = 10.1006/abbi.1995.1182 }}
7. ^{{cite journal |vauthors=Hanukoglu I, Feuchtwanger R, Hanukoglu A | title = Mechanism of corticotropin and cAMP induction of mitochondrial cytochrome P450 system enzymes in adrenal cortex cells | journal = J. Biol. Chem. | volume = 265 | issue = 33 | pages = 20602–8 |date=November 1990 | pmid = 2173715 | doi = | url = http://www.jbc.org/content/265/33/20602.full.pdf }}