Back هيدروكسيلاز-21 Arabic CYP21A2 BS Steroid-21-Hydroxylase German ۲۱-هیدروکسیلاز Persian 21-Hydroxylase French Steroide 21-monoossigenasi Italian ステロイド-21-モノオキシゲナーゼ Japanese 21-hydroxylasis Latin 21-Hydroksylaza Polish 21-hidroxilase Portuguese
| Steroid 21-hydroxylase | |||||||||
|---|---|---|---|---|---|---|---|---|---|
 | |||||||||
| Identifiers | |||||||||
| EC no. | 1.14.14.16 | ||||||||
| CAS no. | 9029-68-9 | ||||||||
| Alt. names | "Cytochrome P450, family 21, subfamily A, polypeptide 2", CYP21A2, CYP21, CYP21B,[1] P45021A2, cytochrome P450c21,[2][3][4] steroid 21-monooxygenase,[5] 21-hydroxylase, 21α-hydroxylase,[6][7] 21β-hydroxylase[8][9] | ||||||||
| 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 | ||||||||
| |||||||||
Steroid 21-hydroxylase is a protein that in humans is encoded by the CYP21A2 gene. The protein is an enzyme that hydroxylates steroids at the C21 position on the molecule.[10][11] Naming conventions for enzymes are based on the substrate acted upon and the chemical process performed. Biochemically, this enzyme is involved in the biosynthesis of the adrenal gland hormones aldosterone and cortisol, which are important in blood pressure regulation, sodium homeostasis and blood sugar control. The enzyme converts progesterone and 17α-hydroxyprogesterone into 11-deoxycorticosterone and 11-deoxycortisol, respectively,[12][13] within metabolic pathways which in humans ultimately lead to aldosterone and cortisol creation—deficiency in the enzyme may cause congenital adrenal hyperplasia.
Steroid 21-hydroxylase is a member of the cytochrome P450 family of monooxygenase enzymes that use an iron-containing heme cofactor to oxidize substrates.
In humans, the enzyme is localized in endoplasmic reticulum membranes of cells in adrenal cortex,[14][15] and is encoded by the CYP21A2 gene which is located near the CYP21A1P pseudogene that has high degree of sequence similarity. This similarity makes it difficult to analyze the gene at the molecular level, and sometimes leads to loss-of-function mutations of the gene due to intergenic exchange of DNA.
- ^ "UniProt". www.uniprot.org. Archived from the original on 28 November 2023. Retrieved 26 November 2023.
- ^ Marino S, Perez Garrido N, Ramírez P, Pujana M, Dratler G, Belgorosky A, Marino R (2020). "Molecular analysis of the CYP21A2 gene in dried blood spot samples". Medicina. 80 (3): 197–202. PMID 32442933.
- ^ Kaewkot A, Boonkaewwan C, Noosud J, Kayan A (November 2017). "Expression level of the cytochrome P450c21 (CYP21) protein correlating to drip loss in pigs". Animal Science Journal. 88 (11): 1855–1859. doi:10.1111/asj.12863. PMID 28677294.
- ^ Mizrachi D, Wang Z, Sharma KK, Gupta MK, Xu K, Dwyer CR, Auchus RJ (May 2011). "Why human cytochrome P450c21 is a progesterone 21-hydroxylase". Biochemistry. 50 (19): 3968–74. doi:10.1021/bi102078e. PMC 3165045. PMID 21446712.
- ^ "Information on EC 1.14.14.16 - steroid 21-monooxygenase - BRENDA Enzyme Database". www.brenda-enzymes.org. Archived from the original on 11 October 2020. Retrieved 21 September 2020.
- ^ Mukangwa M, Takizawa K, Aoki Y, Hamano S, Tetsuka M (February 2020). "Expression of genes encoding mineralocorticoid biosynthetic enzymes and the mineralocorticoid receptor, and levels of mineralocorticoids in the bovine follicle and corpus luteum". The Journal of Reproduction and Development. 66 (1): 75–81. doi:10.1262/jrd.2019-127. PMC 7040213. PMID 31839646.
- ^ Sarafoglou K, Lorentz CP, Otten N, Oetting WS, Grebe SK (July 2012). "Molecular testing in congenital adrenal hyperplasia due to 21α-hydroxylase deficiency in the era of newborn screening". Clinical Genetics. 82 (1): 64–70. doi:10.1111/j.1399-0004.2011.01694.x. PMID 21534945. S2CID 7197547.
- ^ Bergamaschi R, Livieri C, Uggetti C, Candeloro E, Egitto MG, Pichiecchio A, Cosi V, Bastianello S (March 2006). "Brain white matter impairment in congenital adrenal hyperplasia". Archives of Neurology. 63 (3): 413–6. doi:10.1001/archneur.63.3.413. PMID 16540460.
- ^ Marcol W, Kalina-Faska B, Wackermann-Ramos A, Koehler B (2000). "Congenital adrenal hyperplasia conditioned by 21beta-hydroxylase deficiency - clinical considerations". Endokrynologia, Diabetologia I Choroby Przemiany Materii Wieku Rozwojowego (in Polish). 6 (1): 67–9. PMID 14640134.
- ^
This article incorporates public domain material from "NCBI: CYP21A2 cytochrome P450 family 21 subfamily A member 2". Reference Sequence collection. National Center for Biotechnology Information. Retrieved 30 November 2020. 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 endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone. Mutations in this gene cause congenital adrenal hyperplasia. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought to account for many cases of steroid 21-hydroxylase deficiency. Two transcript variants encoding different isoforms have been found for this gene.
- ^ Ryan KJ, Engel LL (March 1957). "Hydroxylation of steroids at carbon 21" (PDF). The Journal of Biological Chemistry. 225 (1): 103–14. doi:10.1016/S0021-9258(18)64913-0. PMID 13416221. Archived (PDF) from the original on 25 March 2020. Retrieved 17 October 2009.
- ^ Pallan PS, Wang C, Lei L, Yoshimoto FK, Auchus RJ, Waterman MR, Guengerich FP, Egli M (May 2015). "Human Cytochrome P450 21A2, the Major Steroid 21-Hydroxylase: structure of the enzyme progesterone substrate complex and rate-limiting c-h bond cleavage". The Journal of Biological Chemistry. 290 (21): 13128–43. doi:10.1074/jbc.M115.646307. PMC 4505568. PMID 25855791.
- ^ Neunzig J, Milhim M, Schiffer L, Khatri Y, Zapp J, Sánchez-Guijo A, et al. (March 2017). "The steroid metabolite 16(β)-OH-androstenedione generated by CYP21A2 serves as a substrate for CYP19A1". The Journal of Steroid Biochemistry and Molecular Biology. 167: 182–191. doi:10.1016/j.jsbmb.2017.01.002. PMID 28065637. S2CID 36860068.
- ^ Guengerich FP, Waterman MR, Egli M (August 2016). "Recent Structural Insights into Cytochrome P450 Function". Trends in Pharmacological Sciences. 37 (8): 625–40. doi:10.1016/j.tips.2016.05.006. PMC 4961565. PMID 27267697.
- ^ Sushko TA, Gilep AA, Usanov SA (June 2012). "Mechanism of intermolecular interactions of microsomal cytochrome P450s CYP17 and CYP21 involved in steroid hormone biosynthesis". Biochemistry. Biokhimiia. 77 (6): 585–92. doi:10.1134/S0006297912060041. PMID 22817457. S2CID 18927484.
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