17alpha-hydroxylase

17α水酸化酵素

関

17-alpha-hydroxylase

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/18 18:08:48」(JST)

wiki en

[Wiki en表示]

Cytochrome P450, family 17, subfamily A, polypeptide 1
Human Cytochrome P450 CYP17A1 PDB. 3ruk
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2C17, 3RUK, 3SWZ, 4NKV, 4NKW, 4NKX, 4NKY, 4NKZ
Identifiers
Symbols	CYP17A1 ; CPT7; CYP17; P450C17; S17AH
External IDs	OMIM: 609300 MGI: 88586 HomoloGene: 73875 ChEMBL: 3522 GeneCards: CYP17A1 Gene
EC number	1.14.99.9, 4.1.2.30
Gene ontology Molecular function • steroid 17-alpha-monooxygenase activity • iron ion binding • oxygen binding • heme binding • 17-alpha-hydroxyprogesterone aldolase activity Cellular component • mitochondrion • endoplasmic reticulum • endoplasmic reticulum membrane • axon • neuronal cell body Biological process • steroid biosynthetic process • androgen biosynthetic process • glucocorticoid biosynthetic process • xenobiotic metabolic process • sex differentiation • steroid metabolic process • sterol metabolic process • hormone biosynthetic process • progesterone metabolic process • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	1586	13074
Ensembl	ENSG00000148795	ENSMUSG00000003555
UniProt	P05093	P27786
RefSeq (mRNA)	NM_000102	NM_007809
RefSeq (protein)	NP_000093	NP_031835
Location (UCSC)	Chr 10: 102.83 – 102.84 Mb	Chr 19: 46.67 – 46.67 Mb
PubMed search	[1]	[2]

Cytochrome P450 17A1, or steroid 17-alpha-monooxygenase, or 17α-hydroxylase/17,20 lyase/17,20 desmolase is an enzyme that in humans is encoded by the CYP17A1 gene. It is found in the zona reticularis of the adrenal cortex. 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. It has both 17alpha-hydroxylase and 17,20-lyase activities, and is a key enzyme in the steroidogenic pathway that produces progestins, mineralocorticoids, glucocorticoids, androgens, and estrogens.

More specifically, CYP17A1 acts upon pregnenolone and progesterone to add a hydroxyl (-OH) group at carbon 17 of the steroid D ring (the hydroxylase activity), or acts upon 17-hydroxyprogesterone and 17-hydroxypregnenolone to split the side-chain off the steroid nucleus (the lyase activity).

Clinical significance

Mutations in this gene are associated with 17 alpha-hydroxylase deficiency, 17 alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia.

The drug abiraterone which is used to treat castration-resistant prostate cancer blocks the biosynthesis of androgens by inhibiting the CYP17A1 enzyme. Abiraterone binds in the active site of the enzyme and coordinates the heme iron through its pyridine nitrogen, mimicking the subtrate.

Steroidogenesis

17α-hydroxylase converts pregnenolone and progesterone to their 17-hydroxy forms, and converts 17-hydroxypregnenolone and 17-hydroxyprogesterone to DHEA and androstenedione, respectively. It corresponds to the downward arrows in this reaction scheme.

Steroidogenesis, showing, at left side, both reactions of 17-alpha hydroxylase, and both actions of 17, 20 lyase.

Additional images

• Pregnenolone

• 17-Hydroxypregnenolone

• Progesterone

• 17-Hydroxyprogesterone

• Steroid numbering

See also

• Congenital adrenal hyperplasia due to 17 alpha-hydroxylase deficiency

References

Further reading

• Miura K, Yasuda K, Yanase T, Yamakita N, Sasano H, Nawata H et al. (Oct 1996). "Mutation of cytochrome P-45017 alpha gene (CYP17) in a Japanese patient previously reported as having glucocorticoid-responsive hyperaldosteronism: with a review of Japanese patients with mutations of CYP17". The Journal of Clinical Endocrinology and Metabolism 81 (10): 3797–801. doi:10.1210/jc.81.10.3797. PMID 8855840. 
• Miller WL, Geller DH, Auchus RJ (1999). "The molecular basis of isolated 17,20 lyase deficiency". Endocrine Research 24 (3-4): 817–25. doi:10.3109/07435809809032692. PMID 9888582. 
• Strauss JF (Nov 2003). "Some new thoughts on the pathophysiology and genetics of polycystic ovary syndrome". Annals of the New York Academy of Sciences 997: 42–8. doi:10.1196/annals.1290.005. PMID 14644808. 
• Haider SM, Patel JS, Poojari CS, Neidle S (Jul 2010). "Molecular modeling on inhibitor complexes and active-site dynamics of cytochrome P450 C17, a target for prostate cancer therapy". Journal of Molecular Biology 400 (5): 1078–098. doi:10.1016/j.jmb.2010.05.069. PMID 20595043. 

External links

• CYP17A1 protein, human at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 先天性副腎過形成の稀な原因 uncommon causes of congenital adrenal hyperplasia
• 2. 原発性無月経の病因、診断、および治療 etiology diagnosis and treatment of primary amenorrhea
• 3. 副腎ステロイド生合成 adrenal steroid biosynthesis
• 4. 21－ヒドロキシラーゼ欠損症による古典的先天性副腎皮質過形成の遺伝学および臨床症状 genetics and clinical presentation of classic congenital adrenal hyperplasia due to 21 hydroxylase deficiency
• 5. 小児における原発性副腎不全の原因および臨床症状 causes and clinical manifestations of primary adrenal insufficiency in children

English Journal

• Initiation of active immunization against testosterone during early puberty alters negative feedback regulation of the hypothalamic-pituitary-testicular axis in rabbits.

• Han XF1, Cheng W1, Chen ZY1, Du XG1, Cao XH1, Zeng XY2.
• Domestic animal endocrinology.Domest Anim Endocrinol.2014 Jul;48:126-35. doi: 10.1016/j.domaniend.2014.04.001. Epub 2014 Apr 12.
• To investigate the effects of antitestosterone immunization, initiated during early puberty, on hypothalamic-pituitary-testicular feedback in rabbits, 16 early pubertal male rabbits were randomly allocated into 2 groups (n = 8), control or immunized against testosterone-3(O-carboxymethyl)oxime-BSA i
• PMID 24906938

• Combined blockade of testicular and locally made androgens in prostate cancer: A highly significant medical progress based upon intracrinology.

• Labrie F.
• The Journal of steroid biochemistry and molecular biology.J Steroid Biochem Mol Biol.2014 Jun 9. pii: S0960-0760(14)00114-9. doi: 10.1016/j.jsbmb.2014.05.012. [Epub ahead of print]
• Recently two drugs, namely the antiandrogen MDV-3100 and the inhibitor of 17α-hydroxylase abiraterone have been accepted by the FDA for the treatment of castration-resistant prostate cancer (CRPC) with or without previous chemotherapy, with a prolongation of overall survival of 2.2-4.8 months. Whil
• PMID 24925260

• Initial experience with abiraterone acetate in patients with castration-resistant prostate cancer.

• Beardo-Villar P1, Ledo-Cepero MJ2, Gavira-Moreno R3, Soto-Delgado M4, Soto-Villalba J2, Alvarez-Ossorio JL2, Juárez-Soto A4.
• Actas urologicas espanolas.Actas Urol Esp.2014 Jun;38(5):339-345. doi: 10.1016/j.acuro.2013.11.004. Epub 2014 Jan 28.
• OBJECTIVE: To describe the results obtained in 25 males with metastatic castration-resistant prostate cancer (MCRPC) treated with abiraterone (AA). A comparative analysis of abiraterone effectiveness and safety between our results and data published in the literature was conducted.MATERIAL AND METHO
• PMID 24480574

Japanese Journal

• Profiles of Circulating Steroid Hormones, Gonadotropins, Immunoreactive Inhibin and Prolactin During Pregnancy in Goats and Immunolocalization of Inhibin Subunits, Steroidogenic Enzymes and Prolactin in the Corpus Luteum and Placenta

• Kandiel Mohamed M. M.,Watanabe Gen,Sosa Gamal A. [他],ABOU EL-ROOS Mahmoud E. A.,ABDEL-GHAFFAR Alaa E.,LI Jun Y.,MANABE Noboru,EL AZAB Abd El Salam I.,TAYA Kazuyoshi
• The Journal of reproduction and development 56(2), 243-250, 2010-04-01
• … Immunohistochemical localization of inhibin alpha, betaA, betaB and steroidogenic enzymes cytochrome P450 aromatase, 3alpha-hydroxysteroid dehydrogenase (3betaHSD), cytochrome 17alpha-hydroxylase P450 and cholesterol side-chain cleavage cytochrome P450 in the cyclic and pregnant goat CL revealed positive immunoreactivity without affinity differences between the luteal and pregnancy stages. …
• NAID 10026324516

• Apparent activities of 21-hydroxylase, 17alpha-hydroxylase and 17,20-lyase are impaired in adrenal incidentalomas

• SADOUL JL.
• Eur J Endocrinol 141, 238-245, 1999
• NAID 30015210287

Related Links

• 17alpha-hydroxylase - definition of 17alpha-hydroxylase in ...

Definition of 17alpha-hydroxylase in the Medical Dictionary. 17alpha-hydroxylase explanation. Information about 17alpha-hydroxylase in Free online English dictionary. What is 17alpha-hydroxylase? Meaning of 17alpha forum ? ...

• 17alpha-Hydroxylase | Fundstellen im Internet | cyclopaedia.net

Fundstellen zu "17alpha-Hydroxylase" im Internet, an Universitäten und in der Literatur... cyclopaedia.net cyclopaedia.net Twittern 17alpha-Hydroxylase 17alpha-Hydroxylase Die Steroid-17alpha-Hydroxylase (auch: Cytochrom die ...

Related Pictures

---

★リンクテーブル★

リンク元	「17α-水酸化酵素」「17α水酸化酵素」
拡張検索	「steroid 17alpha-hydroxylase」「17alpha-hydroxylase deficiency」

「17α-水酸化酵素」

　　[★]

英

17-alpha-hydroxylase, 17alpha-hydroxylase, 17α-hydroxylase

同

17α-ヒドロキシラーゼ、ステロイド17α-水酸化酵素 steroid 17α-hydroxylase、ステロイド17α-モノオキシゲナーゼ steroid 17α-monooxygenase、P-450C17

関

17α水酸化酵素

[show details]

17α-水酸化酵素 : 約 10,300 件
17α-ヒドロキシラーゼ : 59 件

「17α水酸化酵素」

　　[★]

英

17alpha-hydroxylase

関

17α-水酸化酵素

「steroid 17alpha-hydroxylase」

　　[★]

ステロイド17α水酸化酵素、ステロイド17αヒドロキシラーゼ

関

steroid 17-alpha-hydroxylase

「17alpha-hydroxylase deficiency」

　　[★]

17α水酸化酵素欠損症、17αヒドロキシラーゼ欠損症

関

17-alpha-hydroxylase deficiency