AUTOXIDATION OF LIPIDS AND ANTIOXIDATION BY ALPHA-TOCOPHEROL AND UBIQUINOL IN HOMOGENEOUS SOLUTION AND IN AQUEOUS DISPERSIONS OF LIPIDS - UNRECOGNIZED CONSEQUENCES OF LIPID PARTICLE-SIZE AS EXEMPLIFIED BY OXIDATION OF HUMAN LOW-DENSITY-LIPOPROTEIN

Recent studies on the initial stages in oxidation of low density lipoprotein (LDL) have revealed certain previously unrecognized similarities to emulsion polymerization and some quite unexpected features including the following: (i) ascorbate is an extremely effective antioxidant for LDL containing alpha-tocopherol (alpha-TOH); (ii) in the presence of alpha-TOH and in the absence of both ascorbate and ubiquinol 10 (Q10H-2), oxidation of LDL occurs via a free radical chain; (iii) Q10H-2 is a much better antioxidant for LDL than alpha-TOH, although the reverse is true in homogeneous systems. We show here that these problems can be solved on the basis of three simple hypotheses, each of which is based on known chemistry: (i) alpha-TOH in LDL can be regenerated from its radical, alpha-TO., by ascorbate; (ii) in the absence of ascorbate and Q10H-2, the alpha-TOH in LDL acts as a chain-transfer agent rather than as a radical trap; (iii) Q10H-2 is a much more effeCtive chain-breaking antioxidant than alpha-TOH in LDL because the semiquinone radical Q10H. exports its radical character from the LDL into the aqueous phase. Our conclusions imply that the search for better antiatherosclerotic drugs might profitably focus on antioxidants capable of exporting radicals from LDL particles or otherwise increasing the traffic of radicals between particles.