Lipid metabolizing enzyme activities modulated by phospholipid substrate lateral distribution.
Biological membranes contain many domains enriched in phospholipid lipids and there is not yet clear explanation about how these domains can control the activity of phospholipid metabolizing enzymes. Here we used the surface dilution kinetic theory to derive general equations describing how complex substrate distributions affect the activity of enzymes following either the phospholipid binding kinetic model (which assumes that the enzyme molecules directly bind the phospholipid substrate molecules), or the surface-binding kinetic model (which assumes that the enzyme molecules bind to the membrane before binding the phospholipid substrate). Our results strongly suggest that, if the enzyme follows the phospholipid binding kinetic model, any substrate redistribution would increase the enzyme activity over than observed for a homogeneous distribution of substrate. Besides, enzymes following the surface-binding model would be independent of the substrate distribution. Given that the distribution of substrate in a population of micelles (each of them a lipid domain) should follow a Poisson law, we demonstrate that the general equations give an excellent fit to experimental data of lipases acting on micelles, providing reasonable values for kinetic parameters--without invoking special effects such as cooperative phenomena. Our theory will allow a better understanding of the cellular-metabolism control in membranes, as well as a more simple analysis of the mechanisms of membrane acting enzymes.
Facultad de Medicina, Universidad Diego Portales, Avda. Ejército 141, Santiago, Chile. dino.salinas@udp.cl
Dino G
DG
Salinas
Juan G
JG
Reyes
Milton
M
De la Fuente
D002462:Cell Membrane / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D008563:Membrane Lipids / Q000378:metabolism*; D008823:Micelles; D008954:Models, Biological; D010740:Phospholipases / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*
D008563:Membrane Lipids; D008823:Micelles; D010743:Phospholipids; D010740:Phospholipases