11β-羥基類固醇去氫酶1型
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
編輯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
編輯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
編輯參考文獻
編輯- ^ 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
編輯- Human HSD11B1 genome location and HSD11B1 gene details page in the UCSC Genome Browser.
拓展閱讀
編輯- 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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