18-hydroxylation

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Cytochrome P450, family 11, subfamily B, polypeptide 2
Identifiers
Symbols CYP11B2; CPN2; CYP11B; ALDOS; CYP11BL; P-450C18; P450C18; P450aldo
External IDs OMIM: 124080 MGI: 88583 HomoloGene: 73878
EC number 1.14.15.4
RNA expression pattern

More reference expression data
Orthologs
Human Mouse
Entrez 1585 110115
Ensembl ENSG00000179142 n/a
Uniprot P19099 n/a
Refseq NM_000498 (mRNA)
NP_000489 (protein)		 NM_001033229 (mRNA)
NP_001028401 (protein)
Location Chr 8: 143.99 - 144 Mb n/a
Pubmed search [1] [2]

Aldosterone synthase (or 18-hydroxylase) is a steroid hydroxylase cytochrome P450 oxidase enzyme involved in the generation of aldosterone.

This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane. The enzyme has steroid 18-hydroxylase activity to synthesize aldosterone and 18-oxocortisol as well as steroid 11 beta-hydroxylase activity. Mutations in this gene cause corticosterone methyl oxidase deficiency.[1]

It converts 11-deoxycorticosterone to corticosterone, to 18-hydroxycorticosterone, and finally to aldosterone:

11-Deoxycorticosterone

Corticosterone

18-hydroxycorticosterone

Aldosterone

It is found in the zona glomerulosa.

Contents

Additional images

Steroidogenesis, showing aldosterone synthase at right.
Steroidogenesis, showing aldosterone synthase at right.

Corticosteroid biosynthetic pathway in rat

References

  1. ^ "Entrez Gene: CYP11B2 cytochrome P450, family 11, subfamily B, polypeptide 2".

Further reading

  • Helmberg A (1993). "Twin genes and endocrine disease: CYP21 and CYP11B genes.". Acta Endocrinol. 129 (2): 97–108. PMID 8372604. 
  • Slight SH, Joseph J, Ganjam VK, Weber KT (1999). "Extra-adrenal mineralocorticoids and cardiovascular tissue.". J. Mol. Cell. Cardiol. 31 (6): 1175–84. doi:10.1006/jmcc.1999.0963. PMID 10371693. 
  • Stowasser M, Gunasekera TG, Gordon RD (2002). "Familial varieties of primary aldosteronism.". Clin. Exp. Pharmacol. Physiol. 28 (12): 1087–90. PMID 11903322. 
  • Padmanabhan N, Padmanabhan S, Connell JM (2002). "Genetic basis of cardiovascular disease--the renin-angiotensin-aldosterone system as a paradigm.". Journal of the renin-angiotensin-aldosterone system : JRAAS 1 (4): 316–24. doi:10.3317/jraas.2000.060. PMID 11967817. 
  • Lifton RP, Dluhy RG, Powers M, et al. (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. 
  • Mitsuuchi Y, Kawamoto T, Naiki Y, et al. (1992). "Congenitally defective aldosterone biosynthesis in humans: the involvement of point mutations of the P-450C18 gene (CYP11B2) in CMO II deficient patients.". Biochem. Biophys. Res. Commun. 182 (2): 974–9. PMID 1346492. 
  • Pascoe L, Curnow KM, Slutsker L, et al. (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. PMID 1518866. 
  • Pascoe L, Curnow KM, Slutsker L, et al. (1992). "Mutations in the human CYP11B2 (aldosterone synthase) gene causing corticosterone methyloxidase II deficiency.". Proc. Natl. Acad. Sci. U.S.A. 89 (11): 4996–5000. PMID 1594605. 
  • Kawamoto T, Mitsuuchi Y, Toda K, et al. (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. PMID 1741400. 
  • Curnow KM, Tusie-Luna MT, Pascoe L, et al. (1992). "The product of the CYP11B2 gene is required for aldosterone biosynthesis in the human adrenal cortex.". Mol. Endocrinol. 5 (10): 1513–22. PMID 1775135. 
  • Kawainoto T, Mitsuuchi Y, Ohnishi T, et al. (1991). "Cloning and expression of a cDNA for human cytochrome P-450aldo as related to primary aldosteronism.". Biochem. Biophys. Res. Commun. 173 (1): 309–16. PMID 2256920. 
  • Mornet E, Dupont J, Vitek A, White PC (1990). "Characterization of two genes encoding human steroid 11 beta-hydroxylase (P-450(11) beta).". J. Biol. Chem. 264 (35): 20961–7. PMID 2592361. 
  • Martsev SP, Chashchin VL, Akhrem AA (1985). "[Reconstruction and study of a multi-enzyme system by 11 beta-hydroxylase steroids]". Biokhimiia 50 (2): 243–57. PMID 3872685. 
  • Shizuta Y, Kawamoto T, Mitsuuchi Y, et al. (1995). "Inborn errors of aldosterone biosynthesis in humans.". Steroids 60 (1): 15–21. PMID 7792802. 
  • Mitsuuchi Y, Kawamoto T, Miyahara K, et al. (1993). "Congenitally defective aldosterone biosynthesis in humans: inactivation of the P-450C18 gene (CYP11B2) due to nucleotide deletion in CMO I deficient patients.". Biochem. Biophys. Res. Commun. 190 (3): 864–9. PMID 8439335. 
  • Fardella CE, Rodriguez H, Montero J, et al. (1997). "Genetic variation in P450c11AS in Chilean patients with low renin hypertension.". J. Clin. Endocrinol. Metab. 81 (12): 4347–51. PMID 8954040. 
  • Nomoto S, Massa G, Mitani F, et al. (1997). "CMO I deficiency caused by a point mutation in exon 8 of the human CYP11B2 gene encoding steroid 18-hydroxylase (P450C18).". Biochem. Biophys. Res. Commun. 234 (2): 382–5. PMID 9177280. 
  • Peter M, Fawaz L, Drop SL, et al. (1997). "Hereditary defect in biosynthesis of aldosterone: aldosterone synthase deficiency 1964-1997.". J. Clin. Endocrinol. Metab. 82 (11): 3525–8. PMID 9360501. 
  • Taymans SE, Pack S, Pak E, et al. (1998). "Human CYP11B2 (aldosterone synthase) maps to chromosome 8q24.3.". J. Clin. Endocrinol. Metab. 83 (3): 1033–6. PMID 9506770. 

External links

 This oxidoreductase article is a stub. You can help Wikipedia by expanding it.
v • d • e
Oxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14)
1.14.11 - 2-oxoglutarate
1.14.13 - NADH or NADPH
1.14.14 - reduced flavin or flavoprotein
1.14.15 - reduced iron-sulfur protein
11B1 - 11B2 - 11A1
1.14.16 - reduced pteridine
1.14.17 - reduced ascorbate
1.14.18-19 - other
1.14.99 - miscellaneous
v • d • e
Cytochrome P450, oxygenases: steroid hydroxylases - steroidogenesis (EC 1.14)
To pregnenolone
To aldosterone/cortisol
To sex hormones
Other
v • d • e
Cytochromes, oxygenases: cytochrome P450 (EC 1.14)
CYP1
A1, A2, B1
CYP2
A6, A7, A13, B6, C8, C9, C18, C19, D6, E1, F1, J2, R1, S1, U1, W1
CYP3
CYP4
A11, A22, B1, F2, F3, F8, F11, F12, F22, V2, X1, Z1
CYP5-20
CYP5 (A1) - CYP7 (A1, B1) - CYP8 (A1, B1) - CYP11 (A1, B1, B2) - CYP17 (A1) - CYP19 (A1) - CYP20 (A1)
CYP21-51
CYP21 (A2) - CYP24 (A1) - CYP26 (A1, B1, C1) - CYP27 (A1, B1, C1) - CYP39 (A1) - CYP46 (A1) - CYP51 (A1)

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  • This page was last modified on 7 October 2008, at 02:46.

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