title: Effect of oxidation on the properties of apolipoproteins A-I and A-II.
abstract: Purified apolipoprotein A-I has been separated by reversed-phase high performance liquid chromatography (HPLC) into multiple peaks and these peaks have been characterized. One peak, apoA-Ib had a relatively longer retention time on HPLC but its retention time could be shortened by treatment by hydrogen peroxide. CNBr cleavage studies indicated that the differences in apoA-Ib and in its oxidation product, apoA-Ia, were due to the different oxidation states of methionine. This phenomenon was also observed in apoA-II, where methionine oxidation produced two more forms of this apolipoprotein in addition to the native form. These isomers were found to have different secondary structures and affinities for lipid. Model peptide analogs of the amphipathic helix with the same sequence but with methionine and methionine sulfoxide at the nonpolar face of the amphipathic helix were synthesized and studied. It was found that the lipid affinities of these synthetic peptide isomers were very different. They also differed in their secondary structures as studied by circular dichroism (CD). We propose that methionine oxidation introduces hydrophilic residues at the nonpolar face of the amphipathic helical domains of these apolipoproteins and, therefore, alters their secondary structure and lipid affinity.
mesh_terms: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A / Q000032:analysis*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D003488:Cyanogen Bromide; D004591:Electrophoresis, Polyacrylamide Gel; D006861:Hydrogen Peroxide / Q000378:metabolism; D007536:Isomerism; D008623:Mercaptoethanol / Q000378:metabolism; D008854:Microscopy, Electron; D010084:Oxidation-Reduction; D010455:Peptides / Q000138:chemical synthesis
chemical_list: D016632:Apolipoprotein A-I; D016633:Apolipoprotein A-II; D001054:Apolipoproteins A; D010455:Peptides; D008623:Mercaptoethanol; D006861:Hydrogen Peroxide; D003488:Cyanogen Bromide