DISSOCIATION OF ENZYME OLIGOMERS - A MECHANISM FOR ALLOSTERIC REGULATION

Most enzymes exist as oligomers or polymers, and a significant subset of these (perhaps 15% of all enzymes) can reversibly dissociate and re associate in response to an effector ligand. Such a change in subunit assembly usually is accompanied by a change in enzyme activity, provid ing a mechanism for regulation. Two models are described for a physica l mechanism, leading to a change in activity: (1) catalytic activity d epends on subunit conformation, which is modulated by subunit dissocia tion; and (2) catalytic or regulatory sites are located at subunit int erfaces and are disrupted by subunit dissociation. Examples of such en zymes show that both catalytic sites and regulatory sites occur at the junction of 2 subunits. In addition, for 9 enzymes, kinetic studies s upported the existence of a separate regulatory site with significantl y different affinity for the binding of either a substrate or a produc t of that enzyme. Over 40 dissociating enzymes are described from 3 ma jor metabolic areas: carbohydrate metabolism, nucleotide metabolism, a nd amino acid metabolism. Important variables that influence enzyme di ssociation include: enzyme concentration, ligand concentration, other cellular proteins, pH, and temperature. All these variables can be rea dily manipulated in vitro, but normally only the first two are physiol ogical variables. Seven of these enzymes are most active as the dissoc iated monomer, the others as oligomers, emphasizing the importance of a regulated equilibrium between 2 or more conformational states. Exper iments to test whether enzyme dissociation occurs in vivo showed this to be the case in 6 out of 7 studies, with 4 different enzymes.