11β-羥基類固醇去氫酶1型

HSD11B1
已知的結構
PDB	直系同源搜尋: PDBe RCSB
PDBID列表
	4P38、1XU9、2BEL、2ILT、2IRW、2RBE、3BYZ、3BZU、3CH6、3CZR、3D3E、3D4N、3D5Q、3EY4、3FCO、3FRJ、3H6K、3HFG、3OQ1、3PDJ、3QQP、3TFQ、4BB5、4BB6、4C7J、4C7K、4HFR、4HX5、4IJU、4IJV、4IJW、4K1L、4YYZ、1XU7
識別號
別名	HSD11B1；, 11-DH, 11-beta-HSD1, CORTRD2, HDL, HSD11, HSD11B, HSD11L, SDR26C1, hydroxysteroid (11-beta) dehydrogenase 1, hydroxysteroid 11-beta dehydrogenase 1
外部ID	OMIM：600713 MGI：103562 HomoloGene：68471 GeneCards：HSD11B1
EC number	1.1.1.146
相關疾病
	cortisone reductase deficiency 2
基因位置（人類）
染色體	1號染色體
終止	209,734,949 bp
基因位置（小鼠）
染色體	小鼠1號染色體
終止	192,946,383 bp
RNA表現模式
	查閱更多表現資料
基因本體
分子功能	• 11-beta-hydroxysteroid dehydrogenase (NADP+) activity; • oxidoreductase activity; • 11-beta-hydroxysteroid dehydrogenase [NAD(P) activity]; • steroid binding;
細胞組分	• integral component of membrane; • endoplasmic reticulum membrane; • 內質網; • 膜;
生物學過程	• glucocorticoid biosynthetic process; • lung development; • 脂質代謝; • steroid metabolic process;
	Sources:Amigo / QuickGO
直系同源
	3290
	15483
	ENSG00000117594
	ENSMUSG00000016194
	P28845
	P50172
	NM_181755; NM_001206741; NM_005525
	NM_001044751; NM_008288
NP_001193670; NP_005516; NP_861420; NP_001193670.1; NP_005516.1;
	NP_861420.1
	NP_001038216; NP_032314
	維基資料
檢視/編輯人類	檢視/編輯小鼠

11β-羥基類固醇去氫酶1型（HSD11B1），也稱為可的松還原酶，是一種NADPH依賴性酶，在包括肝臟、脂肪組織和中樞神經系統在內的關鍵代謝組織中高度表現。在這些組織中，HSD11B1將可的松還原為活化糖皮質素受體的活性激素皮質醇。屬於短鏈去氫酶家族。

功能

這個基因編碼的蛋白質是一種微粒體酶，催化應激激素皮質醇轉化為非活性代謝物可的松。此外，編碼的蛋白質可以催化相反的反應，即可的松轉化為皮質醇。過多的皮質醇會導致中樞性肥胖，這種基因的一個特殊變異與兒童肥胖和胰島素抵抗有關。在這個基因中發現了兩個編碼相同蛋白質的轉錄變體。^[6]

臨床意義

11β-HSD1被通常用於治療消化性潰瘍的藥物卡賓諾酮抑制。此外，從甘草（glycyrrhiza glabra）根中提取的18α-甘草酸被發現是一種抑制劑。^[7]

水楊酸鹽下調肥胖小鼠脂肪組織中11β-HSD1的表現，從而解釋了阿斯匹靈改善第2型糖尿病血糖控制的原因。^[8]綠茶中的表沒食子兒茶素沒食子酸酯也能有效地抑制這種酶；^[9]綠茶是多種酚類物質的複雜混合物，其含量隨著生產和加工的不同而變化，其中一些酚類物質是已知的改變遺傳表現的HDAC抑制劑。綠茶中的EGCG通常很難被血液吸收。需要更多的研究才能得出明確的結論。^{[來源請求]}

參見

參考文獻

^ 與HSD11B1相關的疾病；在維基數據上查看/編輯參考.
^ ^2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000117594 - Ensembl, May 2017
^ ^3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000016194 - Ensembl, May 2017
^ Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.
^ Entrez Gene: HSD11B1 hydroxysteroid (11-beta) dehydrogenase 1. （原始內容存檔於2010-12-05）.
^ Classen-Houben D, Schuster D, Da Cunha T, Odermatt A, Wolber G, Jordis U, Kueenburg B. Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid. The Journal of Steroid Biochemistry and Molecular Biology. February 2009, 113 (3–5): 248–52. PMID 19429429. doi:10.1016/j.jsbmb.2009.01.009.
^ Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. April 2012, 61 (4): 790–6. PMC 3314355 . PMID 22357964. doi:10.2337/db11-0931.
^ Hintzpeter J, Stapelfeld C, Loerz C, Martin HJ, Maser E. Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. PLoS ONE. 2014-01-03, 9 (1): e84468. Bibcode:2014PLoSO...984468H. PMC 3880318 . PMID 24404164. doi:10.1371/journal.pone.0084468.

外部連結

Human HSD11B1 genome location and HSD11B1 gene details page in the UCSC Genome Browser（英語：UCSC Genome Browser）.

拓展閱讀

White PC, Mune T, Agarwal AK. 11 beta-Hydroxysteroid dehydrogenase and the syndrome of apparent mineralocorticoid excess. Endocrine Reviews. February 1997, 18 (1): 135–56. PMID 9034789. doi:10.1210/er.18.1.135.
Agarwal AK. Cortisol metabolism and visceral obesity: role of 11beta-hydroxysteroid dehydrogenase type I enzyme and reduced co-factor NADPH. Endocrine Research. November 2003, 29 (4): 411–8. PMID 14682470. doi:10.1081/ERC-120026947.
Tomlinson JW, Walker EA, Bujalska IJ, Draper N, Lavery GG, Cooper MS, Hewison M, Stewart PM. 11beta-hydroxysteroid dehydrogenase type 1: a tissue-specific regulator of glucocorticoid response. Endocrine Reviews. October 2004, 25 (5): 831–66. PMID 15466942. doi:10.1210/er.2003-0031.
Wake DJ, Walker BR. Inhibition of 11beta-hydroxysteroid dehydrogenase type 1 in obesity. Endocrine. February 2006, 29 (1): 101–8. PMID 16622297. doi:10.1385/ENDO:29:1:101.
Tannin GM, Agarwal AK, Monder C, New MI, White PC. The human gene for 11 beta-hydroxysteroid dehydrogenase. Structure, tissue distribution, and chromosomal localization. The Journal of Biological Chemistry. September 1991, 266 (25): 16653–8. PMID 1885595.
Graham DL, Oram JF. Identification and characterization of a high density lipoprotein-binding protein in cell membranes by ligand blotting. The Journal of Biological Chemistry. June 1987, 262 (16): 7439–42. PMID 3034894.
Whorwood CB, Mason JI, Ricketts ML, Howie AJ, Stewart PM. Detection of human 11 beta-hydroxysteroid dehydrogenase isoforms using reverse-transcriptase-polymerase chain reaction and localization of the type 2 isoform to renal collecting ducts. Molecular and Cellular Endocrinology. April 1995, 110 (1–2): R7–12. PMID 7545619. doi:10.1016/0303-7207(95)03546-J.
Mune T, Rogerson FM, Nikkilä H, Agarwal AK, White PC. Human hypertension caused by mutations in the kidney isozyme of 11 beta-hydroxysteroid dehydrogenase. Nature Genetics. August 1995, 10 (4): 394–9. PMID 7670488. doi:10.1038/ng0895-394.
Ricketts ML, Verhaeg JM, Bujalska I, Howie AJ, Rainey WE, Stewart PM. Immunohistochemical localization of type 1 11beta-hydroxysteroid dehydrogenase in human tissues. The Journal of Clinical Endocrinology and Metabolism. April 1998, 83 (4): 1325–35. PMID 9543163. doi:10.1210/jc.83.4.1325.
Calvo D, Gómez-Coronado D, Suárez Y, Lasunción MA, Vega MA. Human CD36 is a high affinity receptor for the native lipoproteins HDL, LDL, and VLDL. Journal of Lipid Research. April 1998, 39 (4): 777–88. PMID 9555943.
Odermatt A, Arnold P, Stauffer A, Frey BM, Frey FJ. The N-terminal anchor sequences of 11beta-hydroxysteroid dehydrogenases determine their orientation in the endoplasmic reticulum membrane. The Journal of Biological Chemistry. October 1999, 274 (40): 28762–70. PMID 10497248. doi:10.1074/jbc.274.40.28762.
Sriskanda V, Schwer B, Ho CK, Shuman S. Mutational analysis of Escherichia coli DNA ligase identifies amino acids required for nick-ligation in vitro and for in vivo complementation of the growth of yeast cells deleted for CDC9 and LIG4. Nucleic Acids Research. October 1999, 27 (20): 3953–63. PMC 148661 . PMID 10497258. doi:10.1093/nar/27.20.3953.
Schutte BC, Bjork BC, Coppage KB, Malik MI, Gregory SG, Scott DJ, Brentzell LM, Watanabe Y, Dixon MJ, Murray JC. A preliminary gene map for the Van der Woude syndrome critical region derived from 900 kb of genomic sequence at 1q32-q41. Genome Research. Jan 2000, 10 (1): 81–94. PMC 310500 . PMID 10645953. doi:10.1101/gr.10.1.81 (不活躍 2019-12-11).
Cooper MS, Walker EA, Bland R, Fraser WD, Hewison M, Stewart PM. Expression and functional consequences of 11beta-hydroxysteroid dehydrogenase activity in human bone. Bone. September 2000, 27 (3): 375–81. PMID 10962348. doi:10.1016/S8756-3282(00)00344-6.
Reddy ST, Wadleigh DJ, Grijalva V, Ng C, Hama S, Gangopadhyay A, Shih DM, Lusis AJ, Navab M, Fogelman AM. Human paraoxonase-3 is an HDL-associated enzyme with biological activity similar to paraoxonase-1 protein but is not regulated by oxidized lipids. Arteriosclerosis, Thrombosis, and Vascular Biology. April 2001, 21 (4): 542–7. PMID 11304470. doi:10.1161/01.ATV.21.4.542.
Pácha J, Lisá V, Miksík I. Effect of cellular differentiation on 11beta-hydroxysteroid dehydrogenase activity in the intestine. Steroids. February 2002, 67 (2): 119–26. PMID 11755176. doi:10.1016/S0039-128X(01)00143-X.
Albertin G, Tortorella C, Malendowicz LK, Aragona F, Neri G, Nussdorfer GG. Human adrenal cortex and aldosterone secreting adenomas express both 11beta-hydroxysteroid dehydrogenase type 1 and type 2 genes. International Journal of Molecular Medicine. May 2002, 9 (5): 495–8. PMID 11956655. doi:10.3892/ijmm.9.5.495.
Mazzocchi G, Malendowicz LK, Aragona F, Tortorella C, Gottardo L, Nussdorfer GG. 11beta-Hydroxysteroid dehydrogenase types 1 and 2 are up- and downregulated in cortisol-secreting adrenal adenomas. Journal of Investigative Medicine. July 2002, 50 (4): 288–92. PMID 12109593. doi:10.2310/6650.2002.33012.

[1] 與HSD11B1相關的疾病；在維基數據上查看/編輯參考.

[refGRCh38Ensembl-2] 2.0 ^2.1 ^2.2 GRCh38: Ensembl release 89: ENSG00000117594 - Ensembl, May 2017

[refGRCm38Ensembl-3] 3.0 ^3.1 ^3.2 GRCm38: Ensembl release 89: ENSMUSG00000016194 - Ensembl, May 2017

[4] Human PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Mouse PubMed Reference:. National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-6] Entrez Gene: HSD11B1 hydroxysteroid (11-beta) dehydrogenase 1. （原始內容存檔於2010-12-05）.

[7] Classen-Houben D, Schuster D, Da Cunha T, Odermatt A, Wolber G, Jordis U, Kueenburg B. Selective inhibition of 11beta-hydroxysteroid dehydrogenase 1 by 18alpha-glycyrrhetinic acid but not 18beta-glycyrrhetinic acid. The Journal of Steroid Biochemistry and Molecular Biology. February 2009, 113 (3–5): 248–52. PMID 19429429. doi:10.1016/j.jsbmb.2009.01.009.

[8] Nixon M, Wake DJ, Livingstone DE, Stimson RH, Esteves CL, Seckl JR, Chapman KE, Andrew R, Walker BR. Salicylate downregulates 11β-HSD1 expression in adipose tissue in obese mice and in humans, mediating insulin sensitization. Diabetes. April 2012, 61 (4): 790–6. PMC 3314355 . PMID 22357964. doi:10.2337/db11-0931.

[9] Hintzpeter J, Stapelfeld C, Loerz C, Martin HJ, Maser E. Green tea and one of its constituents, Epigallocatechine-3-gallate, are potent inhibitors of human 11β-hydroxysteroid dehydrogenase type 1. PLoS ONE. 2014-01-03, 9 (1): e84468. Bibcode:2014PLoSO...984468H. PMC 3880318 . PMID 24404164. doi:10.1371/journal.pone.0084468.

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閱論編氧化還原酶：以CH-OH基團為供體的氧化還原酶類（EC 1.1）
1.1.1：以NAD或NADP為受體	醇去氫酶 · 醛酮還原酶（1A1、1B1、1B10、1C1、1C3、1C4、7A2） · 醛醣還原酶 · 醣類去氫酶 · 肉鹼去氫酶 · DXP還原異構酶 · 葡萄糖-6-磷酸去氫酶 · 甘油-3-磷酸去氫酶 · HMG-CoA還原酶 · 3-羥醯輔酶A去氫酶 · β-羥基丁醯輔酶A去氫酶 · 異檸檬酸去氫酶 · 單磷酸次黃嘌呤核苷酸去氫酶 · β-酮脂醯-ACP還原酶 · 乳酸鹽去氫酶 · 蘋果酸去氫酶 · 磷酸葡萄糖酸去氫酶 · L-蘇胺酸去氫酶 · L-木酮醣還原酶 · 山梨醇去氫酶 · 奎尼酸去氫酶羥基類固醇去氫酶：3-β（3-β-HSD、固醇-4-α-羧酸鹽- 3-去氫酶） · 11-β（11β-羥基類固醇去氫酶1型、11-β-羥基類固醇去氫酶2型） · 17-β
1.1.2：以細胞色素為受體	D-乳酸鹽去氫酶 (細胞色素) · D-乳酸鹽去氫酶 (細胞色素c-553) · 甘露醇去氫酶 (細胞色素)
1.1.3：以氧氣為受體	葡萄糖氧化酶 · L-古洛糖酸內酯氧化酶 · 黃嘌呤氧化酶
1.1.4：以二硫化物為受體	維生素K環氧化物還原酶 · 維生素K環氧化物還原酶 (對華法林不敏感)
1.1.5：以醌類似化合物為受體	醌蛋白葡萄糖去氫酶
1.1.99：以其他物質為受體	膽鹼去氫酶 · L-2-羥基戊二酸去氫酶
EC 1.1/2/3/4/5/6/7/8/9/10/11/12/13/14/15/16/17/18/19/20/21/22 · 2.1/2/3/4/5/6/7(2.7.10/11-12)/8/9 · 3.1/2/3/4(3.4.21/22/23/24)/5/6/7/8/9/10/11/12/13 · 4.1/2/3/4/5/6 · 5.1/2/3/4/5/99 · 6.1-3（英語：Template:Ligases CO CS and CN）/4/5-6

閱論編酶
活性	活性位點結合位點催化三聯體負氧離子洞酶催化混雜（英語：Enzyme promiscuity）催化最適酶（英語：Catalytically perfect enzyme）輔因子輔酶酶促反應
調節	異位調節協同性（英語：Cooperativity）酶抑制劑酶活化劑
分類	EC編號蛋白質超家族蛋白質家族酶列表
動力學	酶動力學伊迪-霍夫斯蒂圖（英語：Eadie–Hofstee diagram）哈尼斯-伍爾夫圖（英語：Hanes–Woolf plot）雙倒數圖米氏動力學
類型	EC1 氧化還原酶（列表（英語：List of EC numbers (EC 1)）） EC2 轉移酶（列表（英語：List of EC numbers (EC 2)）） EC3 水解酶（列表（英語：List of EC numbers (EC 3)）） EC4 解離酶（列表（英語：List of EC numbers (EC 4)）） EC5 異構酶（列表（英語：List of EC numbers (EC 5)）） EC6 連接酶（列表（英語：List of EC numbers (EC 6)）） EC7 移位酶（英語：Translocase）（列表（英語：List of EC numbers (EC 7)））