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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