C revealed that methylated arsenic-glutathione complexes are more
stable than arsenic triglutathione. The relevance of these results with regard to the metabolic
fate of arsenite in mammals is discussed.">
亚砷酸甲基化三价Arsenic-Glutathione复合物比他们更稳定的模拟</t我tle>
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no-repeat 6px;background-position:center;padding:16px 0 16px 0;min-width:62px;max-width:62px;} @media (min-width:768px){.iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption .caption-partial-url{padding:16px 0 17px 0;min-width:52px;max-width:52px;}} @media (min-width:992px){.iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption .caption-partial-url{padding:15px 0 17px 0;min-width:60px;max-width:60px;}} .iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption .caption-partial-url:hover{-webkit-text-decoration:none;text-decoration:none;} .iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption-text{font-size:14px;padding:0px 18px 17px 22px;} @media (min-width:768px){.iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption-text{padding:0px 15px 15px 18px;}} @media (min-width:992px){.iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption-text{padding:0px 18px 19px 21px;}} .iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption-text figcaption{margin:0;padding:0;} .iASKvs .floats-partial-section .floats-partial-footer .floats-partial-caption-text svg{max-width:100%;} .iASKvs ol{font-size:16px;padding-left:32px;font-family:STIXGeneral-Regular;line-height:24px;margin:15px 0;} .iASKvs ol li{margin:10px 0;padding-left:10px;word-break:normal;} .iASKvs ol li a{word-break:break-all;} .iASKvs ol li .reflinks{display:block;} .iASKvs ol li .reflinks a{color:#4D8A17;-webkit-text-decoration:none;text-decoration:none;cursor:pointer;} .iASKvs ol li .reflinks a:hover{-webkit-text-decoration:underline;text-decoration:underline;} .iASKvs ol li .reflinks .sep{color:#000000;} .iASKvs .table-wrapper{width:auto;overflow-x:auto;} .iASKvs .table-wrapper::-webkit-scrollbar{-webkit-appearance:none;width:5px;height:5px;} .iASKvs .table-wrapper::-webkit-scrollbar-thumb{border-radius:5px;background-color:rgba(0,0,0,.5);-webkit-box-shadow:0 0 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体积<!-- -->
<!-- -->2008年<!-- -->
<span class="sc-fZwumE cUsFHx">|</年代pan>文章的ID<!-- -->
<!-- -->539082年<!-- -->
<span class="sc-fZwumE cUsFHx">|</年代pan>
<a class="sc-htpNat bUhGXt link sc-fQejPQ duuwge" href="https://doi.org/10.1155/2008/539082" aria-label="Doi-link">https://doi.org/10.1155/2008/539082</a>
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<p>安德鲁·j·珀西尤尔根•盖尔<!-- -->,<!-- -->
<!-- -->”<年代pan class="adjust-article-svg-size">亚砷酸甲基化三价Arsenic-Glutathione复合物比他们更稳定的模拟</年代pan>”,<!-- --><i>生物无机化学与应用</我>,<!-- -->
<!-- -->卷。<!-- -->2008年<!-- -->,<!-- -->
<!-- -->文章的ID<!-- -->539082年<!-- -->,<!-- -->
<!-- -->8<!-- -->
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<!-- -->页面<!-- -->,<!-- -->
<!-- -->2008年<!-- -->。<!-- -->
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<h1 class="sc-iRbamj jZOxOO sc-iSDuPN drIPpp article_title adjust-article-svg-size heading-title">亚砷酸甲基化三价Arsenic-Glutathione复合物比他们更稳定的模拟</h1>
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<span class="">安德鲁·j·珀西<年代up>1</年代up>和</年代pan>
<span class=""><b>尤尔根•盖尔</b><a class="sc-htpNat bUhGXt link" href="mailto:" aria-label="Mail Option"><span class="sc-htoDjs kNoiZu sc-hjRWVT irNWJI icon-colored _2zt-1j0LmaF8UjTQAM413G icon-themeable" title="" font-size="16"></span></a><sup>1</年代up></span>
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<p><sup>1</年代up><span>大学化学系,2500年卡尔加里大学驱动输入加拿大,阿尔伯塔省卡尔加里</年代pan></p>
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<b>学术编辑器:</b>维托Lippolis</div>
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<div class="articleContent__PublcationCol-sc-2yl9jy-5 hgKieC notPublished">
<span class="articleContent__PublicationField-sc-2yl9jy-6 cIribm">收到了</年代pan>
<span class="articleContent__PublicationValue-sc-2yl9jy-7 khHUcu">2008年2月22日</年代pan>
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<span class="articleContent__PublicationField-sc-2yl9jy-6 cIribm">接受</年代pan>
<span class="articleContent__PublicationValue-sc-2yl9jy-7 khHUcu">03年4月2008年</年代pan>
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<span class="articleContent__PublicationField-sc-2yl9jy-6 cIribm">发表</年代pan>
<span class="articleContent__PublicationValue-sc-2yl9jy-7 khHUcu">2008年5月15</年代pan>
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<h4 class="header" id="abstract">文摘</h4>
<p>三价砷的谷胱甘肽复合物砷triglutathione methylarsonous diglutathione,和dimethylarsinous谷胱甘肽是哺乳动物代谢的关键中间体亚砷酸盐,可能代表了砷物种运输从肝脏肾脏的尿排泄。尽管如此,这些复合物的arsenic-sulfur债券的比较稳定没有调查在生理条件下像肝细胞胞质。使用凝胶排阻层析法和glutathione-containing磷酸缓冲盐流动相(5或10毫米谷胱甘肽,pH值7.4)与一个arsenic-specific探测器,我们亚砷酸色谱仪,monomethylarsonous酸,dimethylarsinous酸。根据列形成相应的arsenic-glutathione 4和之间的配合物<年代vg height="11.0375" id="M1" style="vertical-align:-0.17555pt;width:20.200001px;" version="1.1" viewbox="0 0 20.200001 11.0375" width="20.200001" xmlns="http://www.w3.org/2000/svg">
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</svg>C显示,甲基化arsenic-glutathione复合物比砷triglutathione更稳定。这些结果的相关性对亚砷酸代谢的命运在哺乳动物中进行了探讨。</p>
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<h4 id="introduction">1。介绍</h4>
<p>类金属砷()排名第53在地壳中的元素(<a href="#B1">1</a>),主要是在sulfidic发现矿石,如毒砂(FeAsS)和三硫化二砷(<年代ub>2</年代ub>年代<年代ub>3</年代ub>)[<a href="#B2">2</a>]。然而,自然和人为活动,动员地球成因学的砷进入水环境,包括饮用水,亚砷酸盐(如(3))和/或砷酸(如(V))是最普遍的oxyanions [<a href="#B2">2</a>]。因为只有50 - 200的慢性摄入<年代vg height="9.6750002" id="M2" style="vertical-align:-2.29482pt;width:9.6374998px;" version="1.1" viewbox="0 0 9.6374998 9.6750002" width="9.6374998" xmlns="http://www.w3.org/2000/svg">
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</svg>克/天的无机砷与癌症有关的皮肤、肝脏、肺、肾脏和膀胱在人类<a href="#B3">3</a>- - - - - -<a href="#B7">7</a>),人类的暴露浓度的无机的饮用水不安全目前供人类消费的影响<年代vg height="5.7874999" id="M3" style="vertical-align:-0.0pt;width:13.4375px;" version="1.1" viewbox="0 0 13.4375 5.7874999" width="13.4375" xmlns="http://www.w3.org/2000/svg">
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</svg>1亿人(<a href="#B8">8</a>]。事实上,低级中毒悲剧,目前部分地区展开的印度和孟加拉国被称为历史上最大规模中毒(<a href="#B9">9</a>,<a href="#B10">10</a>]。</p>
<p>调查进行的1970年代,whichaimed识别包含在人类尿液代谢物,表示两个五价的organoarsenicals monomethylarsonic酸(MMA (V))和dimethylarsinic酸(DMA (V)),除了一样(III)和(V) (<a href="#B11">11</a>]。最近,两个额外的三价organoarsenicals-monomethylar-sonousacid (MMA (III), CH<年代ub>3</年代ub>(哦)<年代ub>2</年代ub>,图<a href="//www.newsama.com/journals/bca/2008/539082/fig1/" target="_blank">1 (b)</a>,(<a href="#B12">12</a>- - - - - -<a href="#B16">16</a>]]和dimethylarsinous酸[DMA (III), (CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsOH,图<a href="//www.newsama.com/journals/bca/2008/539082/fig1/" target="_blank">1 (c)</a>,(<a href="#B12">12</a>,<a href="#B14">14</a>,<a href="#B15">15</a>]]——也被确认(我们注意,其他为包含代谢物,如thiodimethylarsenopropanoic酸和thiodimethylarsenobutanoic酸,最近发现在人类尿液的代谢物摄取arsenolipids [<a href="#B17">17</a>])。</p>
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亚砷酸溶液物种的pH值7.4 (a), (3), (b) monomethylarsonous酸、MMA (III), (c) dimethylarsinous酸,DMA (III), (d) arsenobetaine AsB, (e)谷胱甘肽,谷胱甘肽,和(f)钠2,3-dimercapto-1-propanesulfonate,纯,]。</table>
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<p>研究哺乳动物代谢(III)(图<a href="//www.newsama.com/journals/bca/2008/539082/fig1/" target="_blank">1(一)</a>)显示高倾向与软配体反应的物种,如硫醇基半胱氨酸(<a href="#B20">20.</a>- - - - - -<a href="#B24">24</a>]。因为cysteine-containing三肽谷胱甘肽(GSH,图<a href="//www.newsama.com/journals/bca/2008/539082/fig1/" target="_blank">1 (e)</a>)是最丰富的内生硫醇在哺乳动物肝细胞胞浆(5毫米<a href="#B25">25</a>),而提取l -半胱氨酸的浓度是0.2 - -0.5毫米<a href="#B26">26</a>]),化学反应(3)连续三摩尔当量的谷胱甘肽砷triglutathione ((SG)<年代ub>3</年代ub>根据(),<a target="_blank">1</a>),可能是这oxyanion的肝代谢的第一步<我>体内。</我><年代pan class="equation"><span class="equation-line"><span class="displayed-label" id="eq1"><img alt="539082. equ.001”年代rc="https://static-01.hindawi.com/articles/bca/volume-2008/539082/figures/539082.equ.001.jpg"></span><span class="equation-label">(1)</年代pan></span></span>鉴于(III)是在大多数哺乳动物的肝酶甲基化<a href="#B27">27</a>- - - - - -<a href="#B30">30.</a>),检测methylarsonous diglutathione (CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>)在(III)治疗大鼠的胆汁<a href="#B31">31日</a>- - - - - -<a href="#B33">33</a>)表明该代谢物形成的肝脏,根据(<a target="_blank">2</a>):<年代pan class="equation"><span class="equation-line"><span class="displayed-label" id="eq2"><img alt="539082. equ.002”年代rc="https://static-01.hindawi.com/articles/bca/volume-2008/539082/figures/539082.equ.002.jpg"></span><span class="equation-label">(2)</年代pan></span></span>DMA (III)的事实也被发现在哺乳动物的尿液<a href="#B12">12</a>,<a href="#B14">14</a>,<a href="#B15">15</a>),化学是可行的,dimethylarsinous谷胱甘肽(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG)也在肝脏形成,根据(<a href="#eq3">3</a>):<年代pan class="equation" id="eq3">
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<p>关于biomethylation机制(3)在哺乳动物中,目前有两个提议通路(<a href="#B34">34</a>,<a href="#B35">35</a>]。第一个涉及的酶氧化甲基化(III) MMA (V),这是具有减少到MMA (III),然后可以接受第二个酶氧化甲基化反应直接存储器存取(V) (<a href="#B29">29日</a>,<a href="#B36">36</a>- - - - - -<a href="#B38">38</a>]。选择最近方案涉及到逐步酶促反应而引起的细胞壁的还原甲基化(SG)<年代ub>3</年代ub>对CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG,使用相同的甲基供体在scheme中one-S-adenosyl-L-methionine [<a href="#B39">39</a>,<a href="#B40">40</a>]。后一种方案,CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>然后氧化MMA (V)从内部生成的H<年代ub>2</年代ub>O<年代ub>2</年代ub>在DMA (V)是在类似的方式从生产(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG。整个biomethylation机制在肝细胞,然而,并非完全理解因为共同的绑定的事件序列(III)内源性small-molecular-mass硫醇(<a href="#B41">41</a>)和甲基化酶是未知的(<a href="#B34">34</a>]。</p>
<p>无论biomethylation机制,(SG)<年代ub>3</年代ub>,CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>,(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG可能扮演重要角色的运输甲基化从肝脏血流[偏方<a href="#B42">42</a>- - - - - -<a href="#B46">46</a>]。尽管如此,我们不太清楚在CH和稳定的债券<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG类似条件下肝细胞胞质(磷酸缓冲盐,pH值7.4,5.0毫米谷胱甘肽,37岁<年代up>°</年代up>C)。此前,作为(SG)的形成<年代ub>3</年代ub>从(哦)<年代ub>3</年代ub>谷胱甘肽,研究了在模拟生理条件下(磷酸缓冲盐,pH值7.4)凝胶排阻色谱(SEC) (<a href="#B22">22</a>]。这个调查显示的列形成(SG)<年代ub>3</年代ub>复杂的强烈依赖于谷胱甘肽浓度的流动相(5 - 7.5毫米青睐),最好是发生在pH值6.0 - -8.0。增加列温度4 - 37<年代up>°</年代up>C(恒定谷胱甘肽在流动相浓度和pH值7.4)导致保留的变化(III)峰值向small-molecular-mass区域,这表明作为债券(SG)<年代ub>3</年代ub>相当不稳定。这一发现是一致的结果获得在其他研究<a href="#B20">20.</a>,<a href="#B47">47</a>- - - - - -<a href="#B49">49</a>]。</p>
<p>哺乳动物的代谢(III)在肝细胞可能由其与胞质共同交互谷胱甘肽(5.0毫米)和蛋白质。为了了解谷胱甘肽的作用在潜在的射流生成(III)代谢产物从肝脏到体循环,我们有色谱仪(III), MMA (III), DMA (III)的情况下,类似于哺乳动物的肝细胞细胞溶质的化学条件(磷酸缓冲盐,5 - 10毫米谷胱甘肽,pH值7.4)在缺乏蛋白质。与温度有关的保留行为调查(III), MMA (III), DMA (III) 4 - 37<年代up>°</年代up>C提供洞察形成(4<年代up>°</年代up>C)和比较稳定(4 - 37<年代up>°</年代up>C)作为债券的列形成复合物。我们的结果构成一个更好的理解的第一步处理的(3)代谢产物从肝脏到血液中。</p>
<h4 id="experimental">2。实验</h4>
<p><span class="statement" id="head1"><span class="statement-title"><i class="statement-title">谨慎</我></年代pan><br><i>由于无机和有机偏方建立细胞毒素,genotoxins和致癌物质<a href="#B4">4</a>,<a href="#B50">50</a>),必须实施措施来减少皮肤和inhalatory曝光。为此,合成和溶液制备进行了手套箱同时佩戴丁腈手套和呼吸面具。</我></年代pan></p>
<h5 id="subsec2.1">2.1。化学物质</h5>
<p>氢氧化钠、磷酸缓冲盐(PBS)平板电脑,谷胱甘肽,钠2,3-dimercapto-1-propanesulfonate(纯数字),蓝色葡聚糖氧化谷胱甘肽(GSSG)和甘氨酸(所有<年代vg height="11.25" id="M5" style="vertical-align:-0.30096pt;width:30.799999px;" version="1.1" viewbox="0 0 30.799999 11.25" width="30.799999" xmlns="http://www.w3.org/2000/svg">
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</g>
</svg>%)从Sigma-Aldrich购买(圣路易斯,密苏里州,美国)。交联葡聚糖G-15 (120<年代vg height="9.6750002" id="M6" style="vertical-align:-2.29482pt;width:12.25px;" version="1.1" viewbox="0 0 12.25 9.6750002" width="12.25" xmlns="http://www.w3.org/2000/svg">
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</text>
</g>
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</svg>m是球形粒子的右旋糖酐与环氧氯丙烷交联,排阻极限:分子质量(毫米)<年代vg height="11.25" id="M7" style="vertical-align:-0.30096pt;width:46.424999px;" version="1.1" viewbox="0 0 46.424999 11.25" width="46.424999" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,11.25)">
<g transform="translate(72,-63)">
<text transform="matrix(1,0,0,-1,-71.95,63.35)">
<tspan style="font-size: 12.50px; " x="0" y="0">
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<tspan style="font-size: 12.50px; " x="12.027886" y="0">
1</t年代pan>
<tspan style="font-size: 12.50px; " x="18.279387" y="0">
5</t年代pan>
<tspan style="font-size: 12.50px; " x="24.530886" y="0">
0</t年代pan>
<tspan style="font-size: 12.50px; " x="30.782387" y="0">
0</t年代pan>
</text>
</g>
</g>
</svg>Da)从通用电气医疗集团购买。亚砷酸钠(NaAsO<年代ub>2</年代ub>)是获得GFS化学品(<年代vg height="11.0625" id="M8" style="vertical-align:-0.30096pt;width:30.799999px;" version="1.1" viewbox="0 0 30.799999 11.0625" width="30.799999" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,11.0625)">
<g transform="translate(72,-63.15)">
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></t年代pan>
<tspan style="font-size: 12.50px; " x="12.027886" y="0">
9</t年代pan>
<tspan style="font-size: 12.50px; " x="18.279387" y="0">
9</t年代pan>
</text>
</g>
</g>
</svg>%)。MMA的来源(III)和直接存储器存取(III)是固体methyldiiodoarsine (CH<年代ub>3</年代ub>AsI<年代ub>2</年代ub>)和液体dimethyliodoarsine (CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsI),合成根据先前建立的程序<a href="#B51">51</a>,<a href="#B52">52</a>]。为了验证这些三价organoarsenicals的纯度,<年代vg height="13.775" id="M9" style="vertical-align:-0.0pt;width:17.5px;" version="1.1" viewbox="0 0 17.5 13.775" width="17.5" xmlns="http://www.w3.org/2000/svg">
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H</t年代pan>
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</g>
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</svg>这些化合物均获得核磁共振光谱(化学变化:1.28 ppm为MMA (III)和1.53 ppm DMA (III))和原始材料(化学变化:1.44 ppm为MMA (V)和1.97 ppm DMA (V))。获得化学变化被发现是类似于那些之前报道这些化合物(<a href="#B48">48</a>,<a href="#B53">53</a>]。Arsenobetaine溴合成(AsB)根据出版过程及其纯度验证了其熔点(实验:225<年代up>°</年代up>C和报道:227<年代up>°</年代up>C) (<a href="#B54">54</a>]。所有的解决方案,包括移动阶段,准备从简单水净化系统与水(电阻率18.2 M<年代vg height="10.6875" id="M10" style="vertical-align:-0.0pt;width:16.225px;" version="1.1" viewbox="0 0 16.225 10.6875" width="16.225" xmlns="http://www.w3.org/2000/svg">
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<tspan style="font-size: 12.50px; " x="9.3022318" y="0">
⋅</t年代pan>
</text>
</g>
</g>
</svg>厘米,微孔)。</p>
<h5 id="subsec2.2">2.2。解决方案</h5>
<p>避免氧化谷胱甘肽在水流动阶段,所有GSH-containing解每个色谱运行前准备的新鲜,在4小时内使用。PBS-buffer是由溶解PBS平板电脑在适当体积的水。解散后monothiol(5或10毫米谷胱甘肽)和/或二硫酚(1毫米纯数字)PBS 400毫升、流动相的pH值调整到7.4与氢氧化钠(4.0米)使用VWR交响SB20 pH值0.45米和过滤<年代vg height="9.6750002" id="M11" style="vertical-align:-2.29482pt;width:12.25px;" version="1.1" viewbox="0 0 12.25 9.6750002" width="12.25" xmlns="http://www.w3.org/2000/svg">
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</svg>米尼龙膜(Alltech)。</p>
<p>作为(III)的水溶液,MMA (III), DMA (III), AsB被溶解NaAsO准备<年代ub>2</年代ub>,CH<年代ub>3</年代ub>AsI<年代ub>2</年代ub>(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsI, AsB在水中得到的浓度为10<年代vg height="9.6750002" id="M12" style="vertical-align:-2.29482pt;width:12.25px;" version="1.1" viewbox="0 0 12.25 9.6750002" width="12.25" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,9.675)">
<g transform="translate(72,-64.26)">
<text transform="matrix(1,0,0,-1,-69.87,66.6)">
<tspan style="font-size: 12.50px; " x="0" y="0">
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</text>
</g>
</g>
</svg>g在20<年代vg height="9.6750002" id="M13" style="vertical-align:-2.29482pt;width:12.25px;" version="1.1" viewbox="0 0 12.25 9.6750002" width="12.25" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,9.675)">
<g transform="translate(72,-64.26)">
<text transform="matrix(1,0,0,-1,-69.87,66.6)">
<tspan style="font-size: 12.50px; " x="0" y="0">
</t年代pan>
</text>
</g>
</g>
</svg>l .人们普遍认为MMA (III)和直接存储器存取(III)是唯一的物种CH水解后形成的<年代ub>3</年代ub>AsI<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsI在水<a href="#B18">18</a>,<a href="#B53">53</a>]。即使所有的色谱图生成与MMA的酸性溶液(III)和直接存储器存取(III)(形成氢碘酸在CH的水解<年代ub>3</年代ub>AsI<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsI的水),保留时间(<我>t<年代ub>r</年代ub></i>)的MMA (III)和直接存储器存取(III)减少<年代vg height="5.7874999" id="M14" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
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</g>
</g>
</svg>20秒时被注入中和解决方案。减轻氧化五价的状态,(III)和MMA (III)解决方案准备每14天而DMA (III)每2 - 3天准备新鲜的<a href="#B55">55</a>- - - - - -<a href="#B57">57</a>]。所有的解决方案都存储在隔玻璃在4瓶<年代up>°</年代up>C。</p>
<h5 id="subsec2.3">2.3。仪表</h5>
<p>液相色谱(LC)系统是由水域510高性能LC权力平等主义的dual-piston泵、一个Rheodyne六端口喷射阀(20<年代vg height="9.6750002" id="M15" style="vertical-align:-2.29482pt;width:12.25px;" version="1.1" viewbox="0 0 12.25 9.6750002" width="12.25" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,9.675)">
<g transform="translate(72,-64.26)">
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<tspan style="font-size: 12.50px; " x="0" y="0">
</t年代pan>
</text>
</g>
</g>
</svg>L样品环),玻璃thermostatable交会列挤满了交联葡聚糖G-15 (<年代vg height="11.075" id="M16" style="vertical-align:-0.3135pt;width:52.237499px;" version="1.1" viewbox="0 0 52.237499 11.075" width="52.237499" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,11.075)">
<g transform="translate(72,-63.14)">
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3</t年代pan>
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1</t年代pan>
<tspan style="font-size: 12.50px; " x="15.278666" y="0">
×</t年代pan>
<tspan style="font-size: 12.50px; " x="26.056252" y="0">
1</t年代pan>
<tspan style="font-size: 12.50px; " x="32.307751" y="0">
。</t年代pan>
<tspan style="font-size: 12.50px; " x="35.433502" y="0">
0</t年代pan>
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</svg>厘米,通用电气医疗集团)和纤维素过滤列头(1.0厘米<年代vg height="8.7875004" id="M17" style="vertical-align:-0.3135pt;width:10.125px;" version="1.1" viewbox="0 0 10.125 8.7875004" width="10.125" xmlns="http://www.w3.org/2000/svg">
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×</t年代pan>
</text>
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</svg>1.0毫米,通用电气医疗集团)。恒温器后4的填充柱在所需的温度,25日或37<年代up>°</年代up>C (NESLAB RTE-7数字一个冷藏浴,热科学),这是平衡与前至少60毫升的流动相化合物注射。1.0毫升/分钟的流量是本研究中使用,每个保留时间是决定一式三份(RSD =<年代vg height="11.0625" id="M18" style="vertical-align:-0.30096pt;width:34.712502px;" version="1.1" viewbox="0 0 34.712502 11.0625" width="34.712502" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,11.0625)">
<g transform="translate(72,-63.15)">
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<</t年代pan>
<tspan style="font-size: 12.50px; " x="12.027886" y="0">
1</t年代pan>
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<tspan style="font-size: 12.50px; " x="21.405136" y="0">
0</t年代pan>
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</g>
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</svg>%)后各个注入砷化合物。</p>
<p>具体检测实现神童,高色散,radial-view icp - aes(美国Teledyne Leeman实验室,哈德逊,NH)通过监控作为原子发射线为189.042 nm。断字的icp - aes LC系统是通过连接LC列退出同心喷雾器的玻璃管,聚乙烯管(38厘米,0.13毫米身份证)。等离子Ar气流率和喷雾器气压19 L / min,射频输出功率为1.3千瓦。时间使用时间分辨扫描进行分析模式(莎莎软件版本3.0)与一个数据点的数据采集速率每1.5秒。导出的数据和平滑(bisquares权重)使用商用软件(SigmaPlot 9.0)。包装的色谱窗口交联葡聚糖G-15列是由注射蓝色葡聚糖水溶液(毫米2 MDa,<我>t<年代ub>r</年代ub></i>~ 6分钟),定义排除卷(<我>V<年代ub>0</年代ub></i>)和甘氨酸(75毫米哒。<我>t<年代ub>r</年代ub></i>~ 15分钟),定义包含卷(<我>V<年代ub>我</年代ub></i>)。的列与水溶液尺寸校准GSSG(毫米<年代vg height="5.7874999" id="M19" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
</text>
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</g>
</svg>600年哒。<我>t<年代ub>r</年代ub></i>~ 10分钟)及谷胱甘肽(毫米<年代vg height="5.7874999" id="M20" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
</text>
</g>
</g>
</svg>300年哒。<我>t<年代ub>r</年代ub></i>~ 13分钟)。所有校准实验用PBS进行流动相(pH值7.4在25岁<年代up>°</年代up>C),而C原子发射线(193.091海里)是监控(图<a href="//www.newsama.com/journals/bca/2008/539082/fig2/" target="_blank">2</a>)。先前的研究已经表明,交联葡聚糖的孔隙大小固定4-37阶段没有明显变化<年代up>°</年代up>C温度范围(<a href="#B22">22</a>]。</p>
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<table>
重叠色谱图尺寸校准标准。山峰从左到右表示蓝色葡聚糖(毫米2 MDa), GSSG(毫米600Da)、谷胱甘肽(毫米30。0Da),甘氨酸(毫米75 Da)。固定相:交联葡聚糖G-15 (cm身份证);流动相:PBS-buffer (pH值7.4),流量:1.0毫升/分钟;检测器:icp - aes在193.091海里;注入量:20l</table>
</div>
</div>
</div>
<h4 id="results-and-discussion">3所示。结果与讨论</h4>
<p>尽管哺乳动物代谢(III)并不完全理解,仍然是(SG)<年代ub>3</年代ub>,CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>,(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG可能发挥重要作用[<a href="#B32">32</a>,<a href="#B43">43</a>,<a href="#B45">45</a>,<a href="#B47">47</a>]。尽管如此,只作为债券的稳定(SG)<年代ub>3</年代ub>被调查的情况下,类似于哺乳动物的肝细胞胞质(<a href="#B22">22</a>]。这是建立使用“保留分析方法”,最初开发研究由LC(可逆oncolumn药物复合物的形成<a href="#B58">58</a>,<a href="#B59">59</a>]。采用这种方法,我们研究了三价的稳定——(GS)<年代ub>x</年代ub>配合物(<年代vg height="10.9125" id="M25" style="vertical-align:-0.17555pt;width:43.737499px;" version="1.1" viewbox="0 0 43.737499 10.9125" width="43.737499" xmlns="http://www.w3.org/2000/svg">
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<tspan style="font-size: 12.50px; " x="10.339981" y="0">
=</t年代pan>
<tspan style="font-size: 12.50px; " x="22.380369" y="0">
1</t年代pan>
<tspan style="font-size: 12.50px; " x="26.556372" y="0">
- - - - - -</t年代pan>
<tspan style="font-size: 12.50px; " x="28.644373" y="0">
3</t年代pan>
</text>
</g>
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</svg>)独立色谱仪(III), MMA (III), DMA (III) SEC列上使用GSH-containing PBS移动阶段(5或10毫米谷胱甘肽,pH值7.4;图<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>)。</p>
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AsB的重叠色谱,(III), MMA (III), DMA (III)作为美国证券交易委员会(SEC)的函数列温度4C(- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -- - - - - -),25岁C(——),或37C()。固定相:交联葡聚糖G-15 (cm身份证);流动相:PBS缓冲包含10毫米谷胱甘肽适应pH值7.4,流量:1.0毫升/分钟;检测器:icp - aes在189.042海里;注入量:20L (10根据复合)g。</table>
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<p>秒被选为分离介质,因为以前的研究为上述三价的反应与谷胱甘肽的形成透露偏方(SG)<年代ub>3</年代ub>(毫米<年代vg height="5.7874999" id="M29" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
</text>
</g>
</g>
</svg>900 Da), CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>(毫米<年代vg height="5.7874999" id="M30" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
</text>
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</svg>600 Da), (CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG(毫米<年代vg height="5.7874999" id="M31" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
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</svg>300 Da) (<a href="#B20">20.</a>,<a href="#B23">23</a>,<a href="#B48">48</a>,<a href="#B49">49</a>,<a href="#B60">60</a>),所有的流体力学半径不同。因此,理想的SEC固定相的分离复合物形成的对列必须有一个适当的分馏窗口。最适合SEC固定相是交联葡聚糖G-15因为它提供了一种排斥的极限<年代vg height="11.25" id="M32" style="vertical-align:-0.30096pt;width:46.424999px;" version="1.1" viewbox="0 0 46.424999 11.25" width="46.424999" xmlns="http://www.w3.org/2000/svg">
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0</t年代pan>
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</svg>达(<a href="#B61">61年</a>]。因为颗粒大小(120<年代vg height="9.6750002" id="M33" style="vertical-align:-2.29482pt;width:12.25px;" version="1.1" viewbox="0 0 12.25 9.6750002" width="12.25" xmlns="http://www.w3.org/2000/svg">
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</svg>米)的固定相(<a href="#B61">61年</a>),然而,相对广泛的色谱峰预计,之前已经观察到的(SG)<年代ub>3</年代ub>(<a href="#B22">22</a>]。</p>
<h5 id="subsec3.1">3.1。随温度而变的对列形成/三价的稳定性(GS)<年代ub>x</年代ub>复合物</h5>
<p>确定温度的影响在列之间形成的复合物的形成和稳定注入三价化合物和流动相硫醇(10毫米谷胱甘肽)、(3)、MMA (III),在交联葡聚糖和DMA (III)色谱仪G-15列4,25岁,37岁<年代up>°</年代up>c .额外的砷的AsB(图<a href="//www.newsama.com/journals/bca/2008/539082/fig1/" target="_blank">1 (d)</a>),这并不与谷胱甘肽,也是色谱仪在这些条件下作为内部标准。观察到的保留行为(III), MMA (III), DMA (III), AsB是描绘在图<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>。</p>
<p>一般来说,所有四个偏方色谱中筛选了窗口。正如所料,AsB(毫米<年代vg height="5.7874999" id="M35" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
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</svg>178 Da)筛选了small-molecular-mass地区之间的谷胱甘肽(毫米<年代vg height="5.7874999" id="M36" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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</svg>300 Da)和甘氨酸(MM 75 Da),不论列温度(<我>t<年代ub>r</年代ub></i>~ 14分钟)。此外,逐步减少峰宽基线(<我>w<年代ub>b</年代ub></i>)与温度的增加从4 - 37<年代up>°</年代up>C可以合理化的扩散速度AsB的毛孔。根据相对应的峰的保留时间(III), MMA (III), DMA (III) (<我>t<年代ub>r</年代ub></i>范围<年代vg height="5.7874999" id="M37" style="vertical-align:-0.0pt;width:13.4375px;" version="1.1" viewbox="0 0 13.4375 5.7874999" width="13.4375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
</text>
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</svg>20分钟,5分钟后<我>V<年代ub>我</年代ub></i>,当PBS-containing移动阶段没有谷胱甘肽(数据未显示)。不详化学之间的交互三价和交联葡聚糖偏方G-15矩阵是最有可能出现这种行为的原因,以前观察(3)类似的固定相材料(<a href="#B22">22</a>]。大概的自由羟基交联葡聚糖G-15矩阵(源于右旋糖酐组)与羟基通过氢键偏方(s);因此,阻碍他们的移民通过列。是化学不可能观察到的保留时间变化4 - 37<年代up>°</年代up>C与GSH-containing移动阶段是由于上述不明化学交互,因为所有注入偏方反应首先在过滤器的孔隙体积与谷胱甘肽(<年代vg height="5.7874999" id="M39" style="vertical-align:-0.0pt;width:10.825px;" version="1.1" viewbox="0 0 10.825 5.7874999" width="10.825" xmlns="http://www.w3.org/2000/svg">
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<h5 id="subsec3.2">3.2。合理化的化学结构对列形成复合物</h5>
<p>的洗脱顺序注射三价在4偏方<年代up>°</年代up>C是(III) (<我>t<年代ub>r</年代ub></i>~ 9分钟),MMA (III) (<我>t<年代ub>r</年代ub></i>~ 10分钟),DMA (III) (<我>t<年代ub>r</年代ub></i>~ 13分钟),这意味着对列形成三价的流体力学半径——(GS)<年代ub>x</年代ub>复合物减少在这个秩序。基于已知的化学亲和力的(III), MMA (III), DMA (III)谷胱甘肽(<a href="#B22">22</a>,<a href="#B23">23</a>,<a href="#B62">62年</a>)(<a target="_blank">1</a>)- (<a href="#eq3">3</a>),此订单的洗脱强烈表明(SG)<年代ub>3</年代ub>,CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>,(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG列头上了。对列形成的证据支持(SG)<年代ub>3</年代ub>(毫米<年代vg height="5.7874999" id="M41" style="vertical-align:-0.0pt;width:16.0375px;" version="1.1" viewbox="0 0 16.0375 5.7874999" width="16.0375" xmlns="http://www.w3.org/2000/svg">
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∼</t年代pan>
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</g>
</svg>900 Da)来自于观察,(3)筛选了<我>V<年代ub>0</年代ub></i>和600毫米校准标准(GSSG),这表明一个复杂与1500年和600年之间的MM Da(图形成的<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>)。同样,CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG最可能形成的柱头,因为保留时间对应MMA (III)和直接存储器存取(III)相同的GSSG(毫米<年代vg height="5.7874999" id="M42" style="vertical-align:-0.0pt;width:13.4375px;" version="1.1" viewbox="0 0 13.4375 5.7874999" width="13.4375" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,5.7875)">
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∼</t年代pan>
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∼</t年代pan>
</text>
</g>
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</svg>300 Da;图<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>vertical-dashed行)。这些三价(GS)<年代ub>x</年代ub>复合物不能结构特征列废水通过电喷雾电离massspectrometry(质)因为电喷雾离子源室的温度(120 - 365年<年代up>°</年代up>3000 C,君子ESI-quadrupole离子阱质谱仪)分离这些热不稳定复合物(CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>分解为180<年代up>°</年代up>C,而(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG分解为100<年代up>°</年代up>C (<a href="#B23">23</a>之前])在电离过程中,质量分析。此外,建议的仪器供应商(力量Daltonics, Billerica,妈,美国),流动相缓冲的盐浓度,可以电喷雾质谱分析必须低于10毫米(总盐利用PBS缓冲<年代vg height="5.7874999" id="M44" style="vertical-align:-0.0pt;width:13.4375px;" version="1.1" viewbox="0 0 13.4375 5.7874999" width="13.4375" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,5.7875)">
<g transform="translate(72,-67.37)">
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∼</t年代pan>
</text>
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</g>
</svg>164毫米)。然而,根据列的对齐与毫米标准(图形成复合物<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>)与三价的倾向与软硫醇化合物反应在水溶液形成配体(SG)<年代ub>3</年代ub>,CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>,(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG [<a href="#B20">20.</a>- - - - - -<a href="#B24">24</a>)强烈表明,后者的物种形成的列。</p>
<h5 id="subsec3.3">3.3。保留的行为(III), MMA (III), DMA (3)</h5>
<p>对保留行为的(III),观察到的峰值4<年代up>°</年代up>C显示大量的尾矿,这表明(SG)<年代ub>3</年代ub>和一个额外的复杂水力半径小,可能卖家(SG)<年代ub>2</年代ub>是列的基础上形成的。增加列温度4 - 37<年代up>°</年代up>C导致4.6分钟保留的转变,(3)峰值向small-molecular-mass地区(图<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>),这可以解释在两种不同的方式。首先,这个峰值与GSSG 25的对齐<年代up>°</年代up>与谷胱甘肽C和37<年代up>°</年代up>C意味着类似的水力半径,这表明肥厚性骨关节病变与肺部转移(SG)<年代ub>2</年代ub>和(HO)<年代ub>2</年代ub>AsSG可能列在这些条件下形成的。即使相对应的峰值(III) 37<年代up>°</年代up>C没有完美结合MM 300校准标准(谷胱甘肽),筛选了接近这个标准比甘氨酸,这表明GS-moiety (III)松散。另外,三个GS-moieties绑定(III) 4<年代up>°</年代up>C可以接受更快的交流增加的温度4 - 37<年代up>°</年代up>C (<a href="#eq1">1</a>)。尽管如此,这些结果充分证实了先前证明作为债券的不稳定性(SG)<年代ub>3</年代ub>(<a href="#B20">20.</a>,<a href="#B22">22</a>,<a href="#B47">47</a>- - - - - -<a href="#B49">49</a>]。</p>
<p>MMA的随温度而变的保留行为(III)和直接存储器存取(III)明显不同(III)因为峰的保留时间对应MMA (III)和直接存储器存取(III)略微转移(<年代vg height="5.7874999" id="M45" style="vertical-align:-0.0pt;width:10.825px;" version="1.1" viewbox="0 0 10.825 5.7874999" width="10.825" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,5.7875)">
<g transform="translate(72,-67.37)">
<text transform="matrix(1,0,0,-1,-71.95,67.42)">
<tspan style="font-size: 12.50px; " x="0" y="0">
∼</t年代pan>
</text>
</g>
</g>
</svg>40秒和4.6分钟,(III))在增加列温度4 - 37<年代up>°</年代up>C(图<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>)。因此,对列对应的三价的形成——(GS)<年代ub>x</年代ub>配合物(<年代vg height="10.825" id="M46" style="vertical-align:-0.11285pt;width:35.924999px;" version="1.1" viewbox="0 0 35.924999 10.825" width="35.924999" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,10.825)">
<g transform="translate(72,-63.34)">
<text transform="matrix(1,0,0,-1,-71.95,63.5)">
<tspan style="font-size: 12.50px; " x="0" y="0">
</t年代pan>
<tspan style="font-size: 12.50px; " x="10.339981" y="0">
=</t年代pan>
<tspan style="font-size: 12.50px; " x="22.380369" y="0">
1</t年代pan>
</text>
</g>
</g>
</svg>或2)柱温度的影响最小。反过来,这意味着在CH和债券<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG更稳定的比(SG)<年代ub>3</年代ub>。总的来说,这些结果,得到在模拟生理条件下,在优秀的符合以前的观测,nonphysiological条件下进行。特别是,这些研究表明,CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG可以合成溶液(<a href="#B23">23</a>),而(SG)<年代ub>3</年代ub>在酒精的解决方案只能合成(酒精明显稳定hydrolytically不稳定和债券)(<a href="#B20">20.</a>,<a href="#B49">49</a>]。</p>
<p>整个随温度而变的保留行为的(III), MMA (III), DMA (III), AsB重复了5毫米GSH-containing流动相(PBS, pH值7.4)在同一秒列。这些结果都是相同的那些见图<a href="//www.newsama.com/journals/bca/2008/539082/fig3/" target="_blank">3</a>(数据未显示),使观察到的比较列形成复合物的稳定性与哺乳动物,无蛋白,肝细胞胞质。</p>
<h5 id="subsec3.4">3.4。生化影响的结果</h5>
<p>ATP-driven GS-X共轭出口水泵,航天飞机xenobiotic-GS-conjugates通过多药耐药性在磷脂双分子层膜蛋白1和2,已知存在于基底外侧膜和顶肝细胞,分别为(<a href="#B42">42</a>- - - - - -<a href="#B45">45</a>]。因此,我们的可能性findingsraise biomethylation (III)的MMA (III)和直接存储器存取(III)在哺乳动物的肝脏可能仅仅出口作为后续(III)到血液中尿通过肾脏排泄。这个相当简单的假设可以解释为什么DMA (III)被发现在大鼠红细胞血红蛋白(<a href="#B63">63年</a>)为什么MMA (III)和直接存储器存取(III)已发现在哺乳动物的尿液<a href="#B12">12</a>- - - - - -<a href="#B16">16</a>]。确切的机制,这些三价偏方出口从肝脏到血液中,然而,需要进一步调查。</p>
<h5 id="subsec3.5">3.5。纯数字的影响以及流动相在复杂地层37<年代up>°</年代up>C</h5>
<p>证实,保留的(3)转移到一个更小的保留时间在来自其它移动阶段增加谷胱甘肽是由列形成的(SG)<年代ub>3</年代ub>,包含两个谷胱甘肽的流动相(5毫米)和纯数字(1毫米,图<a href="//www.newsama.com/journals/bca/2008/539082/fig1/" target="_blank">1 (f)</a>),一种螯合剂,形式更复杂的比谷胱甘肽(III),被调查。这导致的预期增加保留时间(III)<我>V<年代ub>我</年代ub></i>(<年代vg height="14.6" id="M47" style="vertical-align:-3.13504pt;width:45.125px;" version="1.1" viewbox="0 0 45.125 14.6" width="45.125" xmlns="http://www.w3.org/2000/svg">
<g transform="matrix(1.25,0,0,-1.25,0,14.6)">
<g transform="translate(72,-60.32)">
<text transform="matrix(1,0,0,-1,-71.95,63.5)">
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</t年代pan>
</text>
<text transform="matrix(1,0,0,-1,-68.04,60.37)">
<tspan style="font-size: 8.75px; " x="0" y="0">
</t年代pan>
</text>
<text transform="matrix(1,0,0,-1,-60.49,63.5)">
<tspan style="font-size: 12.50px; " x="0" y="0">
≈</t年代pan>
<tspan style="font-size: 12.50px; " x="12.027886" y="0">
1</t年代pan>
<tspan style="font-size: 12.50px; " x="18.279387" y="0">
7</t年代pan>
</text>
</g>
</g>
</svg>分钟),这是与先前的结果[inaccord<a href="#B22">22</a>]。相比之下,没有作为MMA的山峰(III)和直接存储器存取(III)列废水中发现当PBS流动相含有谷胱甘肽(5毫米)和纯数字(1毫米)。目前这种可再生的行为的原因是不理解。</p>
<h4 id="conclusion">4所示。结论</h4>
<p>SEC-based”保留分析方法”的方法结合具体探测器是用来研究的比较列形成三价——(GS)<年代ub>x</年代ub>复合物。这是通过使用移动阶段类似哺乳动物的化学成分,无蛋白肝细胞胞质(5或10毫米谷胱甘肽,PBS, pH值7.4)在4列温度,25日或37<年代up>°</年代up>c单独注射(III), MMA (III)和DMA (III)和观察到的保留行为提供证据列形成更稳定的在CH和债券<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG比(SG)<年代ub>3</年代ub>。这些发现暗示的稳定性作为债券可能会涉及到严重的性格/排泄甲基化三价化合物在哺乳动物。未来的调查应该旨在确定是否CH<年代ub>3</年代ub>(SG)<年代ub>2</年代ub>和(CH<年代ub>3</年代ub>)<年代ub>2</年代ub>AsSG实际上是转移整个肝细胞的膜到血液中<我>体内。</我></p>
<h4 id="acknowledgments">确认</h4>
<p>这项研究是由自然科学和工程研究理事会(NSERC)的加拿大。马克Toonen感激地承认在通用电气医疗集团构建thermojacket玻璃列。</p>
</div>
<div class="xml-content">
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ePub</div><img alt="" class="sc-EHOje jOLhQl sc-bfYoXt cGuwDn" title="" role="presentation" src="data:image/svg+xml;base64,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" height="24"></a>
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<div class="sc-hBbWxd kdRRST">
<div class="sc-dyGzUR cHatnS">
<div>
的观点<年代pan>2229年</年代pan>
</div>
<div>
下载<年代pan>1120年</年代pan>
</div>
</div>
<div>
<div class="sc-drKuOJ kxdGAZ">
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