Zinc protoporphyrin–trimethylamine- N -oxide complex involves cholesterol oxidation causing atherosclerosis,JBIC Journal of Biological Inorganic Chemistry

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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。