Effect of unsaturation in fatty acids on the binding and oxidation by myeloperoxidase: Ramifications for the initiation of atherosclerosis

Oxidation of low density lipoproteins (LDL) in the presence of myeloperoxidase and subsequent uptake of the oxidized LDL by specialized receptors on macrophages has been suggested as an initiating event of atherosclerosis. Oxidized fatty acid chains within the glycerophospholipids of LDL have been implicated as the recognition feature by the receptors. The ability of three fatty acids (oleic, linoleic, and arachidonic acids) typically contained in the lipid portion of the glycerophospholipids to bind and be oxidized by myeloperoxidase was measured by spectroscopically observing interactions of the lipids with the heme prosthetic group of the enzyme. As unsaturation increases in the lipid chain, myeloperoxidase binds and oxidizes the fatty acid more readily, as measured by KD, KM, and kcat. A possible mechanism of the free radical oxidation by myeloperoxidase is discussed.

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