In vivo significance of kinetic constants of protein proteinase inhibitors

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摘要：

We describe the in vivo significance of the kinetic parameters which characterize the interaction between proteinases and protein proteinase inhibitors. Knowledge of the second-order association rate constant k ass and the in vivo inhibitor concentration allows the calculation of the delay time of inhibition, i.e., the time required for complete inhibition of a proteinase in vivo. The influence of biological substrates on the delay time is also analyzed. The extent of substrate breakdown during the delay time of inhibition may be computed from the various constants describing the proteinase/substrate/inhibitor interactions and the biological concentrations of proteinase and inhibitor. The in vivo partition of a proteinase between two inhibitors may be calculated if the kinetic parameters are known. We define a stability time for enzyme-inhibitor complexes as a minimal time during which the complexes may be considered as stable. This time is related to k diss the dissociation rate constant of the reversible enzyme-inhibitor complex or to k, the breakdown rate constant of the complex formed with temporary inhibitors. The overall stability of the complex depends upon the ratio between the inhibitor concentration and K i, the equilibrium dissociation constant of the complex. If this ratio is higher than 1000, a reversible inhibitor behaves like an irreversible one in vivo whatever the enzyme concentration.

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关键词：

Proteins Protease Inhibitors Hydrolysis Kinetics Mathematics Models, Chemical Time Factors

DOI：

10.1016/0006-2944(84)90046-2

被引量：

254

年份：

1984