title: Aluminum-adenine nucleotides as alternate substrates for creatine kinase.
abstract: Aluminum-ATP has previously been shown to be a potent but selective inhibitor of certain kinases (N. C. Furumo and R. E. Viola (1989) Inorg. Chem. 28, 820-823). Because of the selective binding affinity that has been demonstrated, aluminum-ATP was examined as a potential alternate substrate for enzyme-catalyzed phosphoryl-transfer reactions. Of the kinases that have been examined only creatine kinase, which was weakly inhibited by Al-ATP, was found to utilize this metal-nucleotide complex as a substrate. The maximum velocity for this reaction is 0.6% of that observed with Mg-ATP, and a Michaelis constant of 90 microM was measured, which is comparable to that with Mg-ATP. The equilibrium constant for the reaction, measured by phosphorus-31 NMR spectroscopy, is 0.18. This value is indistinguishable from the value determined for the reaction with Mg-ATP as the phosphoryl donor. The rate of interconversion between reactants and products at stoichiometric levels of creatine kinase was found to be quite rapid in the presence of Al3+, indicating that the rate-limiting step in catalytic turnover for this substrate must be a slow rate of substrate binding and/or product release.
authors.affiliation: Department of Chemistry, University of Akron, Ohio 44325-3601.
authors.forename: N C
authors.initials: NC
authors.lastname: Furumo
authors.forename: R E
authors.initials: RE
authors.lastname: Viola
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000535:Aluminum / Q000378:metabolism*; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism*; D007700:Kinetics; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009132:Muscles / Q000201:enzymology; D011817:Rabbits; D013379:Substrate Specificity
chemical_list: D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D000535:Aluminum; D003402:Creatine Kinase; D008274:Magnesium