Regiospecificity of human UDP-glucuronosyltransferase isoforms in chalcone and flavanone glucuronidation determined by metal complexation and tandem mass spectrometry.
Regiospecificity of human UDP-glucuronosyltransferase isoforms in chalcone and flavanone glucuronidation determined by metal complexation and tandem mass spectrometry.
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DOI：
10.1021/np400195z
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发表时间：
2013-06-28
影响因子：
5.1
通讯作者：
Brodbelt JS
中科院分区：
文献类型：
--
作者：
Niemeyer ED;Brodbelt JS
九个人对一系列查尔酮（2'-羟基查尔酮、2',4'-二羟基查尔酮、3,2'-二羟基查尔酮、4,2'-二羟基查尔酮和小豆蔻苷）及其相应的环化黄烷酮（7-羟基黄烷酮、3'-羟基黄烷酮、4'-羟基黄烷酮和山楂素）进行葡萄糖醛酸化对 UDP-葡萄糖醛酸基转移酶 (UGT) 1A 酶进行了评估。柱后金属络合 LC-MS/MS 策略成功地用于产生特征质谱产物离子，将其与洗脱顺序趋势结合使用，以明确识别查尔酮和黄烷酮单葡萄糖醛酸苷，从而可以确定 UGT1A 亚型的区域选择性。 A 环或 B 环上羟基的存在对葡萄糖醛酸化产物的产率和葡萄糖醛酸化发生的位点有显着影响。例如，对于与 UGT1A9 的反应，具有 A 环羟基取代基的二羟基查耳酮的 2'-O-葡萄糖醛酸苷的形成增加。相反，虽然UGT1A8与3,2'-二羟基查尔酮和4,2'-二羟基查尔酮反应产生2'-O-葡萄糖醛酸产物，但小豆蔻素和2',4'-二羟基查尔酮4'位上B环羟基的存在猝灭了OH-2'位上的反应。此外，A环OH-4基团促进了4,2'-二羟基查耳酮与UGT1A1和1A3反应的2'位葡萄糖醛酸化。对于UGT1A7，查耳酮A环上的羟基取代基也促进环化和形成相应的黄烷酮葡萄糖苷酸。
The glucuronidation of a series of chalcones (2'-hydroxychalcone, 2',4'-dihydroxychalcone, 3,2'-dihydroxychalcone, 4,2'-dihydroxychalcone, and cardamonin) and their corresponding cyclized flavanones (7-hydroxyflavanone, 3'-hydroxyflavanone, 4'-hydroxyflavanone, and alpinetin) by nine human UDP-glucuronosyltransferase (UGT) 1A enzymes was evaluated. A post-column metal complexation LC-MS/MS strategy was used successfully to produce characteristic mass spectrometric product ions that were utilized in combination with elution order trends to identify chalcone and flavanone monoglucuronides unambiguously, thus allowing determination of the regioselectivities of the UGT1A isoforms. The presence of hydroxy groups on the A or B-ring had a significant effect on the glucuronide product yield and the site where glucuronidation occurred. For example, for reaction with UGT1A9, formation of the 2'-O-glucuronide was increased for dihydroxychalcones with A-ring hydroxy substituents. In contrast, although UGT1A8 reacted with 3,2'-dihydroxychalcone and 4,2'-dihydroxychalcone to yield 2'-O-glucuronide products, the presence of a B-ring hydroxy group at the 4' position on cardamonin and 2',4'-dihydroxychalcone quenched the reaction at the OH-2' position. Moreover, the A-ring OH-4 group promoted glucuronidation at the 2' position for the reaction of 4,2'-dihydroxychalcone with UGT1A1 and 1A3. For UGT1A7, hydroxy group substituents on the chalcone A-ring also promoted cyclization and formation of the corresponding flavanone glucuronide.
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影响因子：
6.1
作者：
Singh, Rashim;Wu, Baojian;Hu, Ming
通讯作者：
Hu, Ming
影响因子：
7.4
作者：
McClellan, JE;Murphy, JP;Yost, RA
通讯作者：
Yost, RA
影响因子：
7.4
作者：
Davis, BD;Brodbelt, JS
通讯作者：
Brodbelt, JS
DOI：
10.1016/j.jasms.2003.07.002
发表时间：
2003-12-01
影响因子：
3.2
作者：
Pikulski, M;Brodbelt, JS
通讯作者：
Brodbelt, JS
影响因子：
3.2
作者：
Batovska, Daniela Ilieva;Todorova, Iva Todorova
通讯作者：
Todorova, Iva Todorova