Covalent Modification of Creatine Kinase by ATP: Evidence for Autophosphorylation

Abstract

Creatine kinase (CK, EC 2.7.3.2) catalyses the reversible reaction:

$${\text{MgATP}}\, + \,{\text{Creatine}}\,{\text{(Cr)}}\, \leftrightarrow \,{\text{MgADP}}\,{\text{ + }}\,{\text{Phosphocreatine}}\,{\text{(PCr)}}\,{\text{ + }}\,{{\text{H}}^{\text{ + }}}$$

((1))

The reaction mechanism has been classified as rapid equilibrium-type with all evidence pointing to a direct, in-line transfer of the phosphoryl group between bound substrates (Kenyon, Reed 1983), without any direct evidence for a covalent phosphoryl-enzyme intermediate. Only one report so far indicated the possibible existence of such a covalent phosphoryl-enzyme intermediate (Molnar, Lorand 1960). Rat brain CK (Mahadevan et al., 1984) and recently also chicken brain-type creatine kinase have been shown to be partially phosphorylated (Quest et al. 1990); in the latter case the phosphorylated CK correlates with enzyme species showing altered kinetic parameters with respect to the K_m for PCr.