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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/25 17:45:27」(JST)

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Steroid 21-hydroxylase is a cytochrome P450 enzyme that is involved with the biosynthesis of the steroid hormones aldosterone and cortisol.^[1]

In humans, 21-Hydroxylase is encoded by the gene CYP21A2.^[2]

Names and classification[edit]

21-Hydroxylase is also called steroid 21-monooxygenase, 21α-Hydroxylase, and, less commonly 21β-Hydroxylase.

Function[edit]

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 endoplasmic reticulum and hydroxylates steroids at the 21 position. Its activity is required for the synthesis of steroid hormones including cortisol and aldosterone.^[3]

Reaction[edit]

21-Hydroxylase catalyses the hydroxylation of the carbon atom 21 in steroids (adding an "–OH"), which is necessary with the formation of these hormones.

Progesterone

11-deoxycorticosterone

Steroid numbering - #21 is near center top

Pathway[edit]

Human steroidogenesis, showing both reactions of 21-Hydroxylase at center top.

Corticosteroid biosynthetic pathway in the rat.

Clinical significance[edit]

A defect within the CYP21A2 gene causes a disturbance of the development of the enzyme, which leads to congenital adrenal hyperplasia due to 21-hydroxylase deficiency. A related pseudogene is located near this gene; gene conversion events involving the functional gene and the pseudogene are thought account for many cases of steroid 21-hydroxylase deficiency.^[3]

References[edit]

^ Ryan KJ, Engel LL (March 1957). "Hydroxylation of steroids at carbon 21". J. Biol. Chem. 225 (1): 103–14. PMID 13416221.
^ Higashi Y, Yoshioka H, Yamane M, Gotoh O, Fujii-Kuriyama Y (May 1986). "Complete nucleotide sequence of two steroid 21-hydroxylase genes tandemly arranged in human chromosome: a pseudogene and a genuine gene". Proc. Natl. Acad. Sci. U.S.A. 83 (9): 2841–5. doi:10.1073/pnas.83.9.2841. PMC 323402. PMID 3486422.
^ ^a ^b "Entrez Gene: CYP21A2 cytochrome P450, family 21, subfamily A, polypeptide 2".

External links[edit]

GeneReviews/NCBI/NIH/UW entry on 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
OMIM entry on 21-Hydroxylase-Deficient Congenital Adrenal Hyperplasia
Synthesis of Desoxycorticosterone from Progesterone through 21-Hydroxylase (Image)
Steroid 21-Hydroxylase at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

UpToDate Contents

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1. 21－ヒドロキシラーゼ欠損症による非古典的（遅発性）先天性副腎皮質過形成の診断および治療 diagnosis and treatment of nonclassic late onset congenital adrenal hyperplasia due to 21 hydroxylase deficiency
2. 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
3. 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診断 diagnosis of classic congenital adrenal hyperplasia due to 21 hydroxylase deficiency
4. 成人における21－ヒドロキシラーゼ欠損症による古典的な先天性副腎皮質過形成の治療 treatment of classic congenital adrenal hyperplasia due to 21 hydroxylase deficiency in adults
5. 21－ヒドロキシラーゼ欠損症による非古典的（遅発性）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 nonclassic late onset congenital adrenal hyperplasia due to 21 hydroxylase deficiency

English Journal

Imaging features of poorly controlled Congenital Adrenal Hyperplasia in Adults.

Kok HK1, Sherlock M2, Healy NA1, Doody O1, Govender P1, Torreggiani WC1.
The British journal of radiology.Br J Radiol.2015 Jul 2:20150352. [Epub ahead of print]
Congenital adrenal hyperplasia (CAH) is a genetic autosomal recessive condition most frequently as a result of a mutation in the 21-hydroxylase enzyme gene. Patients with poorly controlled CAH can manifest characteristic imaging findings as a result of adrenocorticotrophic hormone stimulation or the
PMID 26133223

Increased cardiovascular and metabolic morbidity in patients with 21-hydroxylase deficiency: a Swedish population-based national cohort study.

Falhammar H1,2, Frisén L3,4, Linden Hirschberg A5,6, Norrby C7, Almqvist C7,8, Nordenskjöld A6,9,10, Nordenström A6,11.
The Journal of clinical endocrinology and metabolism.J Clin Endocrinol Metab.2015 Jun 30:JC20152093. [Epub ahead of print]
CONTEXT: Congenital adrenal hyperplasia (CAH) is lethal in its most severe forms if not treated with glucocorticoids. However, glucocorticoids may increase the risk of cardiovascular and metabolic morbidity.OBJECTIVE: To study cardiovascular and metabolic morbidity in CAH.DESIGN, SETTING AND PARTICI
PMID 26126207

Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase-Deficiency: 13 Years of Neonatal Screening and Follow-up in Bavaria.

Odenwald B1, Dörr HG2, Bonfig W3, Schmidt H4, Fingerhut R5, Wildner M1, Nennstiel-Ratzel U1.
Klinische Padiatrie.Klin Padiatr.2015 Jun 19. [Epub ahead of print]
Background: 21-Hydroxylase deficient (21-OHD) classic congenital adrenal hyperplasia (CAH) is a potentially lethal inherited endocrine disorder. It is included in many neonatal screening programs to prevent morbidity and mortality from salt-wasting and to reduce long-term health problems. This paper
PMID 26090996

Japanese Journal

Neonatal mass screening for 21-hydroxylase deficiency

Clinical Pediatric Endocrinology 25(1), 1-8, 2016
NAID 130005122126

Guidelines for diagnosis and treatment of 21-hydroxylase deficiency (2014 revision)

Clinical Pediatric Endocrinology 24(3), 77-105, 2015
NAID 130005088097

Non-Classic Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency that Developed into Symptomatic Severe Hyponatremia

Internal Medicine 54(10), 1273-1276, 2015
NAID 130005069780

Related Pictures

★リンクテーブル★

リンク元	「副腎皮質ホルモン」「コルチゾール」「21ヒドロキシラーゼ」
拡張検索	「nonclassic 21-hydroxylase deficiency」「21-hydroxylase deficiency」「21-hydroxylase欠損症」「classic 21-hydroxylase deficiency」

「副腎皮質ホルモン」

Cytochrome P450, family 21, subfamily A, polypeptide 2
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2GEG
Identifiers
Symbols	CYP21A2; CA21H; CAH1; CPS1; CYP21; CYP21B; P450c21B
External IDs	OMIM: 613815 MGI: 88591 HomoloGene: 68063 ChEMBL: 2759 GeneCards: CYP21A2 Gene
EC number	1.14.99.10
Gene Ontology
Molecular function	• steroid 21-monooxygenase activity; • steroid binding; • iron ion binding; • steroid hydroxylase activity; • electron carrier activity; • heme binding;
Cellular component	• endoplasmic reticulum membrane;
Biological process	• glucocorticoid biosynthetic process; • mineralocorticoid biosynthetic process; • xenobiotic metabolic process; • steroid metabolic process; • small molecule metabolic process;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	This box: view; talk; edit;

Search
PMC	articles
PubMed	articles
NCBI	proteins

Steroid 21-monooxygenase
Identifiers
EC number	1.14.99.10
CAS number	9029-68-9
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 / EGO
Search
PMC	articles
PubMed	articles
NCBI	proteins

　　[★]

英: adrenocortical hormone
同: 副腎皮質ステロイド adrenocorticoids
関: 副腎皮質刺激ホルモン放出ホルモン、副腎皮質刺激ホルモン; ステロイド
関: 副腎、副腎皮質、ステロイド、コルチコステロイド、ステロイドホルモン、コルチコイド。副腎皮質ホルモン剤

図：SP.891(組織),892(構造式)
副腎皮質の球状層、索状層、網状層で合成される

種類(主要なもののみ)

電解質コルチコイド

球状層から分泌される。アルドステロン

糖質コルチコイド

索状層から分泌される。コルチゾール

副腎アンドロジェン

網状層から分泌される。アンドロステンジオン

コレステロール cholesterol
↓CYP11A1
プレグネノロン pregnenolone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプレグネノロン 17α-hydroxypregnenolone	－－→ CYP17 17α-hydroxylase	デヒドロエピアンドロステロン dehydroepiandrosterone DHEA
↓3β-HSD 3β-hydroxysteroid dehydrogenase		↓3β-HSD		↓3β-HSD
プロゲステロン progesterone	－－→ CYP17 17α-hydroxylase	17α-ヒドロキシプロゲステロン 17α-hydroxyprogesterone	－－→ CYP17 17α-hydroxylase	アンドロステンジオン androstenedione Δ⁴androstene-3,17-dion
↓CYP21 21-hydroxylase		↓CYP21 21-hydroxylase
デオキシコルチコステロン deoxycorticosterone		11-デオキシコルチゾール 11-deoxycortisol
↓CYP11B2　11β-hydroxylase		↓CYP11B1　11β-hydroxylase
コルチコステロン corticosterone		コルチゾール cortisol
↓CYP11B2 18-hydroxylase
18-ヒドロキシコルチコステロン 18-hydroxycorticosterone
↓CYP11B2 18-hydroxydehydrogenase
アルドステロン aldosterone

球状増 zona glomerulosa		索状層 zona fasciculata		網状層 zona reticularis

臨床関連

21-hydroxylaseが正常に機能しないことにより生じる (L.320)

薬理学

副腎皮質ホルモン製剤

副腎皮質から分泌されるホルモン (SP.895)

名称		血漿濃度 (ng/ml)	1日分泌量 (mg/day)
糖質コルチコイド	コルチゾール	40～180	15～20
糖質コルチコイド	コルチコステロン	2～6	2～5
鉱質コルチコイド	アルドステロン	0.05～0.20	0.05～0.15
鉱質コルチコイド	11-DOC	0.05～0.30	0.10～0.20
副腎アンドロジェン	DHEA	2～8	7～15
	DHEA-S	1～4
	アンドロステンジオン	1～2	2～3