Once Again about the Functional Coupling between Mitochondrial Creatine Kinase and Adenine Nucleotide Translocase

T. Yu. Lipskaya^* and M. S. Savchenko

Department of Biochemistry, School of Biology, Lomonosov Moscow State University, Moscow, 119992 Russia; fax: (095) 939-3955

^* To whom correspondence should be addressed.

Received November 16, 2001; Revision received December 27, 2001

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The synthesis of creatine phosphate (CP) by mitochondrial creatine kinase during oxidative phosphorylation was terminated when the mass action ratio of the creatine kinase reaction Gamma = [ADP]*[CP]/[ATP]*[Cr] became equal to the apparent equilibrium constant (K_eq^app)of this reaction. Subsequent excess of Gamma over the K_eq^app was due to an increase in the ADP concentration in the medium. A comparable increase in the ADP concentration also occurred in the absence of creatine (Cr) in the incubation medium. Increase in the ADP concentration was shown to be associated with a decrease in the rate of oxidative phosphorylation and with a relative increase in the ATPase activity of mitochondria during the incubation. A low concentration of ADP (<30 µM) and relatively high concentrations (1-6 mM) of other components of the creatine kinase reaction prevented the detection of the reverse reaction within 10 min after Gamma exceeded the K_eq^app, but the reverse reaction became evident on more prolonged incubation. The reverse reaction was accompanied by a further increase in Gamma. Low ADP concentration in the medium was also responsible for the lack of an immediate conversion of the excess creatine phosphate added although Gamma > K_eq^app. The findings are concluded to be in contradiction with the concept of microcompartment formation between mitochondrial creatine kinase and adenine nucleotide translocase.

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KEY WORDS: mitochondrial creatine kinase, physiological role, adenine nucleotide translocase, functional coupling

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