Oxidation of cholesterol catalyzed by amyloid β-peptide (Aβ)-Cu complex on lipid membrane

A catalytic reaction of H₂O₂ production by an amyloid β-peptide (Aβ)-Cu complex with cholesterol incorporated in a liposome was kinetically analyzed. The Michaelis-Menten model was applied to the H ₂O₂ production reaction using cholesterol as the substrate catalyzed by the Aβ-Cu complex. The K_m value for the Aβ-Cu complex catalytic reaction with cholesterol-containing 1-palmitoyl-2-oleoyl-sn- glycero-3-phosphocholine (POPC) liposomes (K_m=0.436 μM for Aβ(1-40); K_m=0.641 μM for Aβ(1-42)) was found to be smaller than that with cholesterol-containing 1,2-dipalmitoyl-sn-glycero-3- phosphocholine (DPPC) liposomes (K_m=0.585 μM for Aβ(1-40), K_m=0.890 μM for Aβ(1-42)). The results imply that membrane properties could play an important role in the interactions of the Aβ-Cu complex with cholesterol in these liposomes. Considering the physical states of the cholesterol/POPC (liquid disordered phase) and cholesterol/DPPC (liquid ordered phase) liposomes in the present reaction conditions, the data obtained suggests that the H₂O₂-generating activity of the Aβ-Cu complex, accompanied by oxidation of membrane-incorporated cholesterol, could be effected by the phase of the liposome membranes.