Citation

Dhatt S. Journal of Chemical Sciences 2017; 129(12): 1921-1928.

Copyright

(Copyright © 2017)

DOI

10.1007/s12039-017-1400-5

PMID

unavailable

Abstract

Suicide substrate kinetic pathway and a proposed set of indicators, some theoretical and a few practical ones, that can decisively conclude enzyme inactivation are considered. Steady-state approximation is assumed not only when a catalytic amount of enzyme is used but also for any substrate-enzyme ratio. In each situation, adequacy of the approximation is numerically tested. An equation for the rate of inactivation of the enzyme has been derived and employed under suitable approximations to estimate various indicators. Progressive curves for such indicators via numerical simulation are shown that decide impromptu inactivation too. The scheme though is a traditional one, the findings are novel. Graphical Abstract: Synopsis. A few new indicators to identify enzyme inactivation in 'suicide - substrate inhibition' are studied. Validity of the indicators over a wide range of enzyme substrate ratio was investigated. The major pitfalls in prevalent indicators in prior articles their shortcomings were identified. The proposed indicators were justified with analytical and probabilistic arguments. Experimental relevance of the indicators is highlighted. © 2017, Indian Academy of Sciences.

Language: en

Keywords

drug specificity; enzyme inactivation; fractional-life; mechanism-based inhibitor; Suicide inhibitor