Regulation of uridine kinase quaternary structure. Dissociation by the inhibitor CTP.

Uridine kinase from mouse Ehrlich ascites cells can exist in a variety of different aggregation states, from monomer up to aggregates that may contain 32 or more subunits. With very crude enzyme preparations, uridine kinase activity is always associated with several different coexisting molecular weight species. Changes in the aggregation state are produced in the presence of normal effectors (orthophosphate, ATP and CTP) at physiological concentrations. With uridine kinase that has been purified 9,000-fold, enzyme activity is associated with only a single molecular weight species, but is still responsive to the same physiological effectors. In the presence of orthophosphate, uridine kinase has a molecular weight of 380,000 (appropriate for a dodecamer). In the presence of CTP, the enzyme dissociates with concomitant loss of activity. The dissociated enzyme can be reassociated to the native size. These results imply that alteration of the enzyme's quaternary structure by normal effectors constitutes a mechanism for regulating uridine kinase activity in vivo.