Questioning the reliability of estimates of enzyme inhibitor constant: Case of competitive inhibition

TL;DR

This paper critically examines the reliability of commonly used methods for estimating enzyme inhibition constants, highlighting potential inaccuracies and emphasizing the need for careful interpretation of kinetic parameters.

Contribution

It reveals potential errors in estimating enzyme kinetic parameters using Lineweaver-Burk plots and questions the reliability of IC50 measurements under various conditions.

Findings

Lineweaver-Burk plots may produce inaccurate parameter estimates

IC50 values are directly linked to K(I) and K(M) and require careful reassessment

Errors in kinetic parameters vary under steady-state and non-steady-state conditions

Abstract

Reliability of kinetic parameters are crucial in understanding enzyme kinetics within cellular system. The present study suggests a few cautions that need introspection for estimation of parameters like K(M), V(max) and K(I) using Lineweaver-Burk plots. The quality of IC(50) too needs a thorough reinvestigation because of its direct link with K(I) and K(M) values. Inhibition kinetics under both steady-state and non-steady-state conditions are studied and errors in estimated parameters are compared against actual values to settle the question of their adequacy.