A COMPARISON OF DENATURATION AND INACTIVATION RATES OF CREATINE KINASE IN GUANIDINE SOLUTIONS

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Both the denaturation, as followed by UV absorbance and fluorescence changes, and inac-tivation of creatine kinase in guanidine solutions have been found to be first order reactions.In 3 M guanidine, at 30℃, the inactivation rate constant was found to be 5.9 sec~(-1) and thedenaturation rate constant 1.9 sec~(-1). At lower guanidine concentrations, the inactivation rateconstants were only little affected whereas the denaturation rate constants decreased markedly,being of the order of 0.04 in 1 M and 0.004 in 0.5 M guanidine. The kinetics of the inactiva-tion reaction in 0.5 M guanidine was found to be in agreement with a combination of two firstorder reactions. The enzyme lost activity first by a fast reaction with a rate constant onlyslightly lower than the rate constant in 3 M guanidine followed by a slower reaction with a rateconstant of 0.003 sec~(-1). In 0.3 M guanidine, very little change in either UV absorbance or influorescence was observed, but, in sharp contrast, the enzyme lost considerable activity by a fastreaction and this was followed by a slower reaction of inactivation. Even after prolongeddenaturation in 0.5 and 0.3 M guanidine, residual activities of 3.4% and 30% remained res-pectively. The above results suggest a very fragile active site although dissociation of thedimer and reversible guanidine inhibition may also contribute to the initial rapid inactiva-tion. It is also to be noted that the multiphasic courses of inactivation at lower guanidineconcentrations seem to suggest the presence of partly active intermediates during denaturation. Both the denaturation, as followed by UV absorbance and fluorescence changes, and inac-tivation of creatine kinase in guanidine solutions have been found to be first order reactions. In 3 M guanidine, at 30 ° C, the inactivation rate constant was found to be 5.9 sec ~ (-1) and the denaturation rate constant of 1.9 sec ~ (-1). At lower guanidine concentrations, the inactivation rateconstants were only little affected the the denaturation rate constants decreased markedly, being of the order of 0.04 in 1 M and 0.004 in 0.5 M guanidine. The kinetics of the intima-reaction reaction in 0.5 M guanidine was found to be in agreement with a combination of two firstorder reactions. The enzyme lost activity first by a fast reaction with a rate constant only slightly lower than the rate constant in 3 M guanidine followed by a slower reaction with a rate constant of 0.003 sec ~ (-1). In 0.3 M guanidine, very little change in either UV absorbance or influorescence was observed, but, in sharp contrast, the enzyme lost considerably activity by a fast response and this was followed by a slower reaction of inactivation. Even after prolonged denaturation in 0.5 and 0.3 M guanidine, residual activities of 3.4% and 30% remained res-pectively. The above results suggest a very fragile active site dissociation of thedimer and reversible guanidine inhibition may also contribute to the initial rapid inactiva- tion. It is also to be noted that the multiphasic courses of inactivation at lower guanidineconcentrations seem to suggest the presence of partly active intermediates during denaturation.
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