Steroid-17 α -hydroxylase
| Steroid-17 α -hydroxylase | ||
|---|---|---|
|
||
| Crystal structure of human cytochrome P450 17A1 according to PDB 3ruk | ||
| Properties of human protein | ||
| Mass / length primary structure | 511 amino acids | |
| Cofactor | Hamm | |
| Identifier | ||
| Gene name | CYP17A1 | |
| External IDs | ||
| Enzyme Classifications | ||
| EC, category | 1.14.99.9 , monooxygenase | |
| Response type | Hydroxylation | |
| Substrate | Steroid + AH 2 + O 2 | |
| Products | 17 α -hydroxysteroid + A + H 2 O | |
| EC, category | 4.2.1.30 , lyase | |
| Response type | Deacetylation | |
| Substrate | 17alpha-hydroxysteroid | |
| Products | 17-keto steroid + acetic acid | |
| Occurrence | ||
| Parent taxon | Eukaryotes | |
| Orthologue | ||
| human | House mouse | |
| Entrez | 1586 | 13074 |
| Ensemble | ENSG00000148795 | ENSMUSG00000003555 |
| UniProt | P05093 | P27786 |
| Refseq (mRNA) | NM_000102 | NM_007809 |
| Refseq (protein) | NP_000093 | NP_031835 |
| Gene locus | Chr 10: 102.83 - 102.84 Mb | Chr 19: 46.67 - 46.67 Mb |
| PubMed search | 1586 |
13074
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The steroid-17 α -hydroxylase (also: cytochrome P450 17, CYP17 ) is the enzyme that in eukaryotes the hydroxylation and subsequent deacetylation of steroids at the 17-position catalyzed . This reaction is not only necessary for the biosynthesis of the hormones dehydroepiandrosterone (DHEA) and androstenedione (ASD), but also for the breakdown of steroids ( biotransformation ). The enzyme is likely a membrane protein. Mutations in CYP17A1 - gene are the cause of congenital adrenal hyperplasia type 5 .
Catalyzed reactions
The main catalyzed reaction is hydroxylation:
+ A H 2 + O 2 + A + H 2 O
As an example, the 17-hydroxylation of progesterone is 17 α shown hydroxyprogesterone. Pregnenolone is also hydroxylated in this way. Under certain conditions such as phosphorylation of the enzyme and the presence of enough electrons, acetic acid can be split off. This reaction is 17 α -hydroxyprogesterone aldolase (abbreviated 17,20-lyase ) and takes place at the same center as the hydroxylation. As with hydroxylation, the pregnenolone derivative can also serve as a substrate:
Clinical significance
The inhibitor of the steroid 17 α -hydroxylase abiraterone has been used in the treatment of castration-resistant prostate cancer since 2011 .
literature
- Miller WL: Androgen biosynthesis from cholesterol to DHEA . In: Mol. Cell. Endocrinol. . 198, No. 1-2, December 2002, pp. 7-14. PMID 12573809 .
- Auchus RJ: Overview of dehydroepiandrosterone biosynthesis . In: Semin. Reprod. Med. . 22, No. 4, November 2004, pp. 281-8. doi : 10.1055 / s-2004-861545 . PMID 15635496 .
Individual evidence
- ↑ Homologues at inParanoid
- ↑ UniProt P05093
- ↑ Bernhard Kleine: Hormones and the hormonal system . 2nd Edition. Springer, Berlin 2010, ISBN 978-3-642-00901-3 .
- ↑ Bhangoo A, Aisenberg J, Chartoffe A, et al. : Novel mutation in cytochrome P450c17 causes complete combined 17alpha-hydroxylase / 17,20-lyase deficiency . In: J. Pediatr. Endocrinol. Metab. . 21, No. 2, February 2008, pp. 185-90. PMID 18422032 .
- ↑ CJ Ryan et al .: Phase I clinical trial of the CYP17 inhibitor abiraterone acetate demonstrating clinical activity in patients with castration-resistant prostate cancer who received prior ketoconazole therapy. Journal of Clinical Oncology 28 (9): 1481-8,2010
Web links
- Jassal / reactome: Hydroxylation of pregnenolone to form 17alpha-hydroxypregnenolone
- Jassal / reactome: Side chain cleavage of 17alpha-hydroxypregnenolone to yield DHA
- Jassal / reactome: Hydroxylation of progesterone to form 17alpha-hydroxyprogesterone
- Jassal / reactome: Side chain cleavage of 17alpha-hydroxyprogesterone to yield 4-androstene-3,17-dione