Lipid-dependent membrane enzymes. A kinetic model for cooperative activation in the absence of cooperativity in lipid binding.
The dependence of integral membrane enzymes on lipid activators in analyzed in terms of multiple binding site kinetics. Rate equations for an enzyme with n independent and indentical lipid binding sites are derived for the case that enzyme activity is proportional to the total amount of lipid bound, or that only fully substituted enzyme is active. A third equation applies to the case that lipids bind with infinite cooperativity to give fully substituted and active enzyme. None of the three models was entirely consistent with existing experimental data. The following kinetic model is shown to accommodate the degree of cooperativity observed in lipid activation experiments as well as the number of independent lipid-binding sites determined by electron-spin resonance measurements. The membrane enzyme is assumed to have n non-interacting and identical lipid-binding sites. Only fully substituted enzyme (ELn) and the next most highly substituted forms such as ELn-1 and ELn-2 may possess enzyme activity. These assumptions lead to cooperativity in activation. Cooperativity reaches a maximum when enzyme activity starts to appear with about 80% of the full lipid substitution. The increase in cooperativity is accompanied by a decrease in the lipid concentration required for half-maximal activation. Further kinetic aspects of a dynamic boundary lipid layer around integral membrane enzymes are discussed.
D000494:Allosteric Regulation; D001665:Binding Sites; D002462:Cell Membrane / Q000201:enzymology*; D055598:Chemical Phenomena; D002621:Chemistry; D004789:Enzyme Activation; D007700:Kinetics; D008563:Membrane Lipids / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008956:Models, Chemical; D011485:Protein Binding
D008563:Membrane Lipids; D008565:Membrane Proteins