Propagation rate constants for the peroxidation of sterols on the biosynthetic pathway to cholesterol.
Propagation rate constants for the peroxidation of sterols on the biosynthetic pathway to cholesterol.
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DOI：
10.1016/j.chemphyslip.2017.01.006
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发表时间：
2017-10
影响因子：
3.4
通讯作者：
Porter NA
中科院分区：
文献类型：
--
作者：
Lamberson CR;Muchalski H;McDuffee KB;Tallman KA;Xu L;Porter NA
胆固醇的自由基链自动氧化和形成的氧化产物，即氧甾醇，几十年来一直是深入研究的焦点。甾醇前体如 7-脱氢胆固醇 (7-DHC) 和去莫甾醇及其氧甾醇的过氧化作用受到的关注较少。在遗传条件或接触小分子导致组织和体液中这些生物合成中间体增加的情况下，这些甾醇前体的过氧化可能变得很重要。例如，7-DHC 的过氧化传播速率常数约为胆固醇的 200 倍，并且在毁灭性的人类遗传病史密斯-莱姆利-奥皮茨综合征 (SLOS) 中，这种甾醇的水平升高。通过竞争动力学方法（即过氧自由基时钟）测定胆固醇生物合成途径中甾醇中间体过氧化的传播速率常数。在这项工作中，指定了 Bloch 和 Kandutsch-Russell 途径中的 Lathosterol、zymostenol、desmosterol、7-de Hydrodesmosterol 和其他甾醇的传播速率常数，这些速率常数与甾醇的结构特征相关。此外，对于尚未确定氧甾醇产物的甾醇，提出了潜在的氧甾醇产物。
The free radical chain autoxidation of cholesterol and the oxidation products formed, i.e. oxysterols, have been the focus of intensive study for decades. The peroxidation of sterol precursors to cholesterol such as 7-dehydrocholesterol (7-DHC) and desmosterol as well as their oxysterols has received less attention. The peroxidation of these sterol precursors can become important under circumstances in which genetic conditions or exposures to small molecules leads to an increase of these biosynthetic intermediates in tissues and fluids. 7-DHC, for example, has a propagation rate constant for peroxidation some 200 times that of cholesterol and this sterol is found at elevated levels in a devastating human genetic condition, Smith-Lemli-Opitz syndrome (SLOS). The propagation rate constants for peroxidation of sterol intermediates on the biosynthetic pathway to cholesterol were determined by a competition kinetic method, i.e. a peroxyl radical clock. In this work, propagation rate constants for lathosterol, zymostenol, desmosterol, 7-dehydrodesmosterol and other sterols in the Bloch and Kandutsch-Russell pathways are assigned and these rate constants are related to sterol structural features. Furthermore, potential oxysterols products are proposed for sterols whose oxysterol products have not been determined.
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影响因子：
3.3
作者：
Xu L;Porter NA
通讯作者：
Porter NA
影响因子：
3.5
作者：
Cross JL;Iben J;Simpson CL;Thurm A;Swedo S;Tierney E;Bailey-Wilson JE;Biesecker LG;Porter FD;Wassif CA
通讯作者：
Wassif CA
影响因子：
15
作者：
Xu L;Porter NA
通讯作者：
Porter NA
影响因子：
3.5
作者：
Krakowiak, PA;Wassif, CA;Porter, FD
通讯作者：
Porter, FD
影响因子：
120.7
作者：
CASTELLI, WP;GARRISON, RJ;KANNEL, WB
通讯作者：
KANNEL, WB