Abstract
Multiple-equilibrium equations were solved to investigate the individual and separate effects of Mg2+, Mn2+, Ca2+, ATP4-, and their complexes on the kinetics of brain adenylate cyclase. The effects of divalent metals and/or ATP4- (in excess of their participation in complex formation) were determined and, from the corresponding apparent affinity values, the following kinetic constants were obtained: Km(MgATP) = 1.0 mM, Ki(ATP4-) = 0.27 mM, Km(MnATP) = 0.07 mM, and Ki(CaATP) = 0.015 mM. MgATP, MnATP, ATP4-, and CaATP were shown to compete for the active site of the enzyme. Hence, it is proposed that endogenous metabolites with a strong ligand activity for divalent metals, such as citrate and some amino acids, become integrated into a metabolite feedback control of the enzyme through the release of ATP4- from MgATP. Ca2+ fluxes may participate in the endogenous regulation of adenylate cyclase by modifying the level of CaATP. The free divalent metals show an order of affinity K0.5(Ca2+) = 0.02 mM, K0.5(Mn2+) = 3.8 mM, K0.5(Mg2+) - 4.7 mM, and an order of activity Mn2+ greater than Mg2+ greater than Ca2+. The data indicate that Mn2+ and Mg2+ ions may compete for a regulatory site distinct from the active site and increase Vm withou...Continue Reading
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