A catalytic reaction of H2O2 production by an amyloid beta-peptide (A beta)-Cu complex with cholesterol incorporated in a liposome was kinetically analyzed. The Michaelis-Menten model was applied to the H2O2 production reaction using cholesterol as the substrate catalyzed by the A beta-Cu complex. The K-m value for the A beta-Cu complex catalytic reaction with cholesterol-containing 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) liposomes (K-m=0.436 mu M for A beta(1-40); K-m=0.641 mu M for A beta(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 mu M for A beta(1-40), K-m=0.890 mu M for A beta(1-42)). The results imply that membrane properties could play an important role in the interactions of the A beta-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-gencrating activity of the A beta-Cu complex, accompanied by oxidation of membrane-incorporated cholesterol, could be effected by the phase of the liposome membranes.