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氧化甾醇:化学合成、生物合成及生物活性

Oxysterols: chemical synthesis, biosynthesis and biological activities.

作者信息

Parish E J, Nanduri V B, Kohl H H, Taylor F R

出版信息

Lipids. 1986 Jan;21(1):27-30. doi: 10.1007/BF02534299.

DOI:10.1007/BF02534299
PMID:3959767
Abstract

As a class of compounds, oxysterols have demonstrated a wide variety of biological properties. Due to the general interest in these compounds, new methods of chemical synthesis have been developed to provide them for biological investigation. The specific inhibition by oxysterols of cholesterol biosynthesis in mammalian cells has been shown to result primarily from a decrease in cellular levels of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity. Recent evidence suggests these cellular responses may be mediated by an oxysterol binding protein found in the cytosol of many lines of cultured cells. In certain instances, oxysterols have been shown to be produced in biological systems. These results support the supposition that oxysterols may regulate sterol biosynthesis at the cellular level. Included herein are the inhibitory effects of 9 alpha, 11 alpha-epoxycholest-7-en-3 beta-ol cholest-8-en-3 beta-ol-7-one and cholest-8-en-3 beta-ol-11-one on HMG-CoA reductase activity and their relative affinities for a cytosolic binding protein.

摘要

作为一类化合物,氧化甾醇已显示出多种多样的生物学特性。由于对这些化合物的普遍关注,已开发出新的化学合成方法来制备它们用于生物学研究。已表明氧化甾醇对哺乳动物细胞中胆固醇生物合成的特异性抑制主要是由于细胞内3-羟基-3-甲基戊二酰辅酶A(HMG-CoA)还原酶活性水平降低所致。最近的证据表明,这些细胞反应可能由许多培养细胞系的细胞质中发现的一种氧化甾醇结合蛋白介导。在某些情况下,已证明氧化甾醇在生物系统中产生。这些结果支持氧化甾醇可能在细胞水平调节甾醇生物合成的推测。本文包括9α,11α-环氧胆甾-7-烯-3β-醇、胆甾-8-烯-3β-醇-7-酮和胆甾-8-烯-3β-醇-11-酮对HMG-CoA还原酶活性的抑制作用及其对细胞质结合蛋白的相对亲和力。

相似文献

1
Oxysterols: chemical synthesis, biosynthesis and biological activities.氧化甾醇:化学合成、生物合成及生物活性
Lipids. 1986 Jan;21(1):27-30. doi: 10.1007/BF02534299.
2
Inhibitors of sterol synthesis. Chemical syntheses, properties and effects of 4,4-dimethyl-15-oxygenated sterols on sterol synthesis and on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells.甾醇合成抑制剂。4,4-二甲基-15-氧化甾醇在培养的哺乳动物细胞中对甾醇合成及3-羟基-3-甲基戊二酰辅酶A还原酶活性的化学合成、性质及作用。
Chem Phys Lipids. 1988 Jul;47(3):187-207. doi: 10.1016/0009-3084(88)90012-6.
3
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J Lipid Res. 1980 Jul;21(5):571-84.
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Chem Phys Lipids. 1988 Feb;46(2):147-54. doi: 10.1016/0009-3084(88)90125-9.
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Chemical synthesis of 4,4'-dimethyl-7-oxygenated sterols. Inhibitors of 3-hydroxy-3-methylglutaryl reductase.4,4'-二甲基-7-氧化甾醇的化学合成。3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂。
Chem Phys Lipids. 1984 Dec;36(2):179-88. doi: 10.1016/0009-3084(84)90070-7.
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Inhibitors of sterol synthesis. Chemical synthesis and properties of 3 beta-hydroxy-25,26,26,26,27,27,27-heptafluoro-5 alpha-cholest-8(14)-en-15-one and 25,26,26,26,27,27,27-heptafluorocholesterol and their effects on 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured mammalian cells.甾醇合成抑制剂。3β-羟基-25,26,26,26,27,27,27-七氟-5α-胆甾-8(14)-烯-15-酮和25,26,26,26,27,27,27-七氟胆固醇的化学合成与性质及其对培养哺乳动物细胞中3-羟基-3-甲基戊二酰辅酶A还原酶活性的影响。
J Lipid Res. 1993 Oct;34(10):1805-23.
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Further studies on the inhibition of sterol biosynthesis in animal cells by 15-oxygenated sterols.关于15-氧化固醇对动物细胞中固醇生物合成抑制作用的进一步研究。
Chem Phys Lipids. 1979 Nov;25(3):265-85. doi: 10.1016/0009-3084(79)90111-7.
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J Lipid Res. 1989 Feb;30(2):247-61.
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Inhibition of sterol biosynthesis in L cells and mouse liver cells by 15-oxygenated sterols.15-氧化甾醇对L细胞和小鼠肝细胞中甾醇生物合成的抑制作用。
J Biol Chem. 1977 Dec 25;252(24):8975-80.
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Experientia. 1980 May 15;36(5):518. doi: 10.1007/BF01965773.

引用本文的文献

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Lipids. 2007 Feb;42(1):35-40. doi: 10.1007/s11745-006-3000-x. Epub 2007 Jan 16.
2
Remote functionalization of the steroid side-chain.甾体侧链的远程官能化
Lipids. 1997 Dec;32(12):1325-30. doi: 10.1007/s11745-006-0171-4.
3
Side-chain oxysterol regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity.侧链氧化甾醇对3-羟基-3-甲基戊二酰辅酶A还原酶活性的调节

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Selective oxidation of steroidal allylic alcohols using pyrazole and pyridinium chlorochoromate.使用吡唑和氯铬酸吡啶鎓对甾体烯丙醇进行选择性氧化。
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Inhibitors of sterol synthesis. Hypocholesterolemic action of dietary 9 alpha-fluoro-5 alpha-cholest-8(14)-en-3 beta-ol-15-one.固醇合成抑制剂。膳食中9α-氟-5α-胆甾-8(14)-烯-3β-醇-15-酮的降胆固醇作用。
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Sterol biosynthesis.甾醇生物合成
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