関: 17-alpha-hydroxylase

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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)

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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).^[1]

Clinical significance

Mutations in this gene are associated with 17 alpha-hydroxylase deficiency, 17 alpha-hydroxylase/17,20-lyase deficiency, pseudohermaphroditism, and adrenal hyperplasia.^[2]

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.^[3]

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

References

^ Boulpaep EL, Boron, WF (2005). Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. p. 1180. ISBN 1-4160-2328-3.
^ "Entrez Gene: CYP17A1 cytochrome P450, family 17, subfamily A, polypeptide 1".
^ PDB: 3ruk ; DeVore NM, Scott EE (Feb 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature 482 (7383): 116–9. doi:10.1038/nature10743. PMC 3271139. PMID 22266943.

External links

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

UpToDate Contents

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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 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」

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
	v; t; e;

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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

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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

[isbn1-4160-2328-3-1] Boulpaep EL, Boron, WF (2005). Medical physiology: a cellular and molecular approach. St. Louis, Mo: Elsevier Saunders. p. 1180. ISBN 1-4160-2328-3.

[2] "Entrez Gene: CYP17A1 cytochrome P450, family 17, subfamily A, polypeptide 1".

[pmid22266943-3] PDB: 3ruk ; DeVore NM, Scott EE (Feb 2012). "Structures of cytochrome P450 17A1 with prostate cancer drugs abiraterone and TOK-001". Nature 482 (7383): 116–9. doi:10.1038/nature10743. PMC 3271139. PMID 22266943.

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17alpha-hydroxylase