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 (CH 3 ) 3 N + –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.