Kinetic manifestations of structural self-organization for the components of the pyruvate dehydrogenase complex. A...

The structure-function organization of mammalian pyruvate dehydrogenase complex (PDC) is considered. The linear size of the complex components in relation to the size of their fragments and mean distances between potentially active sites are estimated. A kinetic model for the complex with core subunits divided into conformational classes characterized by their different activities is discussed. The kinetic features of this model are compared with the features of the model for the core subunits not divided into classes. Curves are described for the activity of PDC versus time for various activities of the kinase and the phosphatase as dependent on their binding to more or less active core subunits. The results show that spatially distributed multiple active sites in the multi-enzyme complex can drastically change their full activity in time without any marked changes in the rate constants of the elementary reaction steps due only to spatially changed reaction pathways. A new type of regulation discussed for PDC reveals unusual regulatory abilities for complexes of this family.