11β-羟基类固醇脱氢酶1型

HSD11B1
已知的結構
PDB	直系同源搜索: 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
别名	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（人类）
染色体	1號染色體
终止	209,734,949 bp
基因位置（小鼠）
染色体	小鼠1号染色体
终止	192,946,383 bp
RNA表达模式
	查阅更多表达数据
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; • 内质网; • 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
	維基數據
檢視/編輯人類	檢視/編輯小鼠

11β-羟基类固醇脱氢酶1型（HSD11B1），也称为可的松还原酶，是一种NADPH依赖性酶，在包括肝脏、脂肪组织和中枢神经系统在内的关键代谢组织中高度表达。在这些组织中，HSD11B1将可的松还原为激活糖皮质激素受体的活性激素皮质醇。属于短链脱氢酶家族。

功能

这个基因编码的蛋白质是一种微粒体酶，催化应激激素皮质醇转化为非活性代谢物可的松。此外，编码的蛋白质可以催化相反的反应，即可的松转化为皮质醇。过多的皮质醇会导致中枢性肥胖，这种基因的一个特殊变异与儿童肥胖和胰岛素抵抗有关。在这个基因中发现了两个编码相同蛋白质的转录变体。^[6]

临床意义

11β-HSD1被通常用于治疗消化性溃疡的药物卡宾诺酮抑制。此外，从甘草（glycyrrhiza glabra）根中提取的18α-甘草酸被发现是一种抑制剂。^[7]

水杨酸盐下调肥胖小鼠脂肪组织中11β-HSD1的表达，从而解释了阿司匹林改善2型糖尿病血糖控制的原因。^[8]绿茶中的表没食子儿茶素没食子酸酯也能有效地抑制这种酶；^[9]绿茶是多种酚类物质的复杂混合物，其含量随着生产和加工的不同而变化，其中一些酚类物质是已知的改变遗传表达的HDAC抑制剂。绿茶中的EGCG通常很难被血液吸收。需要更多的研究才能得出明确的结论。^{[來源請求]}

参见

参考文献

^ 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. （原始内容存档于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.

外部链接

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

拓展阅读

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 (不活跃 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. （原始内容存档于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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查论编氧化還原酶：以CH-OH基团为供体的氧化还原酶类（EC 1.1）
1.1.1：以NAD或NADP为受体	醇脫氫酶 · 醛酮还原酶（1A1、1B1、1B10、1C1、1C3、1C4、7A2） · 醛糖还原酶 · 糖类脱氢酶 · 肉碱脱氢酶 · DXP还原异构酶 · 葡萄糖-6-磷酸脱氢酶 · 甘油-3-磷酸脱氢酶 · HMG-CoA还原酶 · 3-羟酰辅酶A脱氢酶 · β-羟基丁酰辅酶A脱氢酶 · 异柠檬酸脱氢酶 · 单磷酸次黄嘌呤核苷酸脱氢酶 · β-酮脂酰-ACP还原酶 · 乳酸盐脱氢酶 · 苹果酸脱氢酶 · 磷酸葡萄糖酸脱氢酶 · L-苏氨酸脱氢酶 · L-木酮糖还原酶 · 山梨醇脱氢酶 · 奎尼酸脱氢酶羟基类固醇脱氢酶：3-β（3-β-HSD、固醇-4-α-羧酸盐- 3-脱氢酶） · 11-β（11β-羟基类固醇脱氢酶1型、11-β-羟基类固醇脱氢酶2型） · 17-β
1.1.2：以细胞色素为受体	D-乳酸盐脱氢酶 (细胞色素) · D-乳酸盐脱氢酶 (细胞色素c-553) · 甘露醇脱氢酶 (细胞色素)
1.1.3：以氧气为受体	葡萄糖氧化酶 · L-古洛糖酸内酯氧化酶 · 黄嘌呤氧化酶
1.1.4：以二硫化物为受体	维生素K环氧化物还原酶 · 维生素K环氧化物还原酶 (对华法林不敏感)
1.1.5：以醌类似化合物为受体	醌蛋白葡萄糖脱氢酶
1.1.99：以其他物质为受体	胆碱脱氢酶 · L-2-羟基戊二酸脱氢酶
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（英语：Template:Ligases CO CS and CN）/4/5-6

查论编酶
活性	活性位点结合位点催化三联体负氧离子洞酶催化混杂（英语：Enzyme promiscuity）催化最适酶（英语：Catalytically perfect enzyme）辅因子辅酶酶促反应
调节	别构调节协同性（英语：Cooperativity）酶抑制剂酶激活剂
分类	EC編號蛋白质超家族蛋白质家族酶列表
动力学	酶动力学伊迪-霍夫斯蒂图（英语：Eadie–Hofstee diagram）哈尼斯-伍尔夫图（英语：Hanes–Woolf plot）双倒数图米氏动力学
类型	EC1 氧化還原酶（列表（英语：List of EC numbers (EC 1)）） EC2 轉移酶（列表（英语：List of EC numbers (EC 2)）） EC3 水解酶（列表（英语：List of EC numbers (EC 3)）） EC4 裂合酶（列表（英语：List of EC numbers (EC 4)）） EC5 異構酶（列表（英语：List of EC numbers (EC 5)）） EC6 連接酶（列表（英语：List of EC numbers (EC 6)）） EC7 移位酶（英语：Translocase）（列表（英语：List of EC numbers (EC 7)））