11β-羟基类固醇脱氢酶1型
（重定向自HSD11B1）
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
[编辑]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
[编辑]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
[编辑]参考文献
[编辑]- ^ 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
[编辑]- Human HSD11B1 genome location and HSD11B1 gene details page in the UCSC Genome Browser.
拓展阅读
[编辑]- 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.
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- 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.
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- 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).
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- 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.
