Two related phenolic antioxidants with opposite effects on vitamin E content in low density lipoproteins oxidized by ferrylmyoglobin: consumption vs regeneration.Arch Biochem Biophys. 1995 Nov 10; 323(2):373-81.AB
Endogenous alpha-tocopherol of low density lipoprotein (LDL) particles exposed to ferrylmyoglobin (iron in the form of FeIV = O) vanishes as a function of myoglobin concentration. After alpha-tocopherol depletion, subsequent heavy lipid peroxidation is prevented by caffeic and p-coumaric acids, i.e., phenolic acids present in foods and beverages, by a mechanism involving the one-electron transfer reaction between the phenols and the ferrylmyoglobin, with formation of metmyoglobin and the corresponding phenoxyl radicals from caffeic and p-coumaric acids, as previously discussed. Caffeic acid delays alpha-tocopherol consumption when present before oxidation challenging and restores alpha-tocopherol when added halfway during the reaction. Conversely, p-coumaric acid accelerates the rate of alpha-tocopherol consumption when added either before or during the oxidation reaction. In LDL enriched with alpha-tocopherol, caffeic acid induces an inhibition period of oxidation longer than that expected from the sum of discrete periods characteristic of the phenolic acid and alpha-tocopherol. Surprisingly, p-coumaric acid decreases the peroxidation chain rate. Similar effects of these phenolic acids on alpha-tocopherol consumption were observed in a Triton X-100 micellar system, i.e., in the absence of a peroxidation chain reaction. Results suggest that caffeic acid acts synergistically with alpha-tocopherol, extending the antioxidant capacity of LDL by recycling alpha-tocopherol from the alpha-tocopherol radical (i.e., alpha-tocopheroxyl radical). By contrast, the phenoxyl radical from p-coumaric acid (produced by electron-transfer reaction between phenolic acid and ferrylmyoglobin) oxidizes alpha-tocopherol. However, in spite of alpha-tocopherol consumption, the exchange reaction recycling p-coumaric acid can still afford an antioxidant protection to LDL on basis of the chain-breaking activity of p-coumaric acid. These results emphasize the biological relevance of small structural modifications of phenols on the interaction with alpha-tocopherol in LDL. The significance of these results in the context of atherosclerosis is discussed.