Vitamin E in human low-density lipoprotein. When and how this antioxidant becomes a pro-oxidant.
Uptake of oxidatively modified low-density lipoprotein (LDL) by cells in the arterial wall is believed to be an important early event in the development of atherosclerosis. Because vitamin E is the major antioxidant present in human lipoproteins, it has received much attention as a suppressor of LDL lipid oxidation and as an epidemiological marker for ischaemic heart disease. However, a careful examination of lipid peroxidation in LDL induced by a steady flux of aqueous peroxyl radicals has demonstrated that, following consumption of endogenous ubiquinol-10, the rate of peroxidation (i) declines as vitamin E is consumed, (ii) is faster in the presence of vitamin E than following its complete consumption, (iii) is substantially accelerated by enrichment of the vitamin in LDL, either in vitro or by diet, and (iv) is virtually independent of the applied radical flux. We propose that perodixation is propagated within lipoprotein particles by reaction of the vitamin E radical (i.e. alpha-tocopheroxyl radical) with polyunsaturated fatty acid moieties in the lipid. This lipid peroxidation mechanism, which can readily be rationalized by the known chemistry of the alpha-tocopheroxyl radical and by the radical-isolating properties of fine emulsions such as LDL, explains how reagents which reduce the alpha-tocopheroxyl radical (i.e. vitamin C and ubiquinol-10) strongly inhibit lipid peroxidation in vitamin E-containing LDL.
Bowry
V W
VW
Biochemistry Group, Heart Research Institute, Sydney, New South Wales, Australia.
Ingold
K U
KU
Stocker
R
R
D005231:Fatty Acids, Unsaturated / Q000737:chemistry; D005609:Free Radicals; D006801:Humans; D066298:In Vitro Techniques; D008054:Lipid Peroxides / Q000737:chemistry; D008077:Lipoproteins, LDL / Q000737:chemistry*; D010084:Oxidation-Reduction; D014810:Vitamin E / Q000737:chemistry*
D005231:Fatty Acids, Unsaturated; D005609:Free Radicals; D008054:Lipid Peroxides; D008077:Lipoproteins, LDL; D014810:Vitamin E