Time course of oxysterol formation during in vitro oxidation of low density lipoprotein.
Cholesterol oxidation products (oxysterols) have been implicated in several aspects of atherogenesis; they affect key enzymes in cholesterol homeostasis, induce calcification in vascular cells and possess cytotoxic properties. Oxysterols are formed during oxidative modification of low density lipoprotein (LDL). Using a recently developed method based on isotope dilution-mass spectrometry, the kinetics of formation of oxysterols during oxidation of LDL by cupric ions or soybean lipoxygenase was studied. The same products, mainly 7- and 5-oxygenated cholesterol, were formed by the two oxidation methods. Virtually no side-chain oxidized oxysterols were formed. During the oxidations, preferentially esterified cholesterol was consumed and consumption of polyunsaturated fatty acids and formation of conjugated dienes preceded the appearance of oxysterols. Cholesterol 7-hydroperoxides potential cytotoxins, were present in LDL oxidized by copper or lipoxygenase.
Dzeletovic
S
S
Department of Medical Laboratory Sciences and Technology, Karolinska Institute, Sweden.
Babiker
A
A
Lund
E
E
Diczfalusy
U
U
D002784:Cholesterol / Q000031:analogs & derivatives / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D003300:Copper / Q000494:pharmacology; D004587:Electrophoresis, Agar Gel; D005231:Fatty Acids, Unsaturated / Q000378:metabolism; D006888:Hydroxycholesterols / Q000378:metabolism; D007653:Ketocholesterols / Q000378:metabolism; D007700:Kinetics; D008077:Lipoproteins, LDL / Q000378:metabolism*; D008084:Lipoxygenase / Q000378:metabolism; D013058:Mass Spectrometry; D010084:Oxidation-Reduction; D010545:Peroxides / Q000378:metabolism; D013025:Glycine max / Q000201:enzymology; D013237:Stereoisomerism
D002788:Cholesterol Esters; D005231:Fatty Acids, Unsaturated; D006888:Hydroxycholesterols; D007653:Ketocholesterols; D008077:Lipoproteins, LDL; D010545:Peroxides; C041011:cholesterol 7-hydroperoxide; D003300:Copper; D002784:Cholesterol; D008084:Lipoxygenase