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Zinc protoporphyrin–trimethylamine- N -oxide complex involves cholesterol oxidation causing atherosclerosis
JBIC Journal of Biological Inorganic Chemistry ( IF 2.7 ) Pub Date : 2021-03-13 , DOI: 10.1007/s00775-021-01861-z
Navendu Paul 1 , Rudra Sarkar 1 , Sabyasachi Sarkar 2
Affiliation  

Metabolism of food protein by gut microbes produce trimethylamine which on oxidation by hepatic flavin-containing monooxygenases is transformed to trimethylamine-N-oxide (TMAO). TMAO has recently been implicated as a biomarker for atherosclerosis. TMAO, as (CH3)3N+–O), is ionic and so a hydrophilic molecule that is freely available in blood plasma. For the effective interaction with lipid-soluble molecules, TMAO should be phase transferred to the lipid site. We show that the free TMAO is effectively bonded to zinc protoporphyrin IX dimethyl ester [ZnPPDME] to yield [TMAOZnPPDME] using phase transfer reaction. The zinc protoporphyrin IX, [ZnPP], in general, available in blood may form [TMAOZnPP] complex. The nature of such interaction between TMAO and [ZnPP] has been structurally shown using a model complex, [TMAOZnTPP] (TPP = tetraphenylporphyrin). These complexes readily move from the polar plasma to the non-polar (lipid) site to act as the oxo-transfer agent to oxidize cholesterol causing atherosclerosis. Chromatographic and circular dichroism (CD) studies show that either TMAO or [ZnPP] alone cannot oxidize cholesterol.

Graphic abstract

Free TMAO bonded with zinc-protoporphyrin IX, [ZnPP], in blood plasma as [TMAOZnPP] is transported to the lipid site and this is the reacting species to oxidize cholesterol causing atherosclerosis.



中文翻译:


原卟啉锌-三甲胺-N-氧化物复合物参与胆固醇氧化,导致动脉粥样硬化



肠道微生物对食物蛋白质的代谢产生三甲胺,三甲胺被肝脏含黄素单加氧酶氧化后转化为三甲胺-N-氧化物(TMAO)。 TMAO 最近被认为是动脉粥样硬化的生物标志物。 TMAO,作为(CH 3 ) 3 N + –O - ),是离子性的,因此是一种亲水性分子,可以在血浆中自由获得。为了与脂溶性分子有效相互作用,TMAO应该相转移到脂质位点。我们表明,利用相转移反应,游离的 TMAO 可以有效地与锌原卟啉 IX 二甲酯 [ZnPPDME] 结合,生成 [TMAOZnPPDME]。一般来说,血液中的锌原卟啉 IX ([ZnPP]) 可形成 [TMAOZnPP] 复合物。 TMAO 和 [ZnPP] 之间这种相互作用的性质已通过模型复合物 [TMAOZnTPP](TPP = 四苯基卟啉)在结构上得到了展示。这些复合物很容易从极性血浆移动到非极性(脂质)位点,充当氧化转移剂,氧化胆固醇,导致动脉粥样硬化。色谱和圆二色性 (CD) 研究表明,TMAO 或 [ZnPP] 单独不能氧化胆固醇。

 图文摘要


血浆中与锌原卟啉 IX ([ZnPP]) 结合的游离 TMAO 作为 [TMAOZnPP] 被转运至脂质位点,这是氧化胆固醇的反应物质,导致动脉粥样硬化。

更新日期:2021-03-15
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