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Dynamic disorder in quasi-equilibrium enzymatic systems.

ABSTRACT: Conformations and catalytic rates of enzymes fluctuate over a wide range of timescales. Despite these fluctuations, there exist some limiting cases in which the enzymatic catalytic rate follows the macroscopic rate equation such as the Michaelis-Menten law. In this paper we investigate the applicability of macroscopic rate laws for fluctuating enzyme systems in which catalytic transitions are slower than ligand binding-dissociation reactions. In this quasi-equilibrium limit, for an arbitrary reaction scheme we show that the catalytic rate has the same dependence on ligand concentrations as obtained from mass-action kinetics even in the presence of slow conformational fluctuations. These results indicate that the timescale of conformational dynamics--no matter how slow--will not affect the enzymatic rate in quasi-equilibrium limit. Our numerical results for two enzyme-catalyzed reaction schemes involving multiple substrates and inhibitors further support our general theory.

SUBMITTER: Chaudhury S

PROVIDER: S-EPMC2927515 | biostudies-literature | 2010 Aug

REPOSITORIES: biostudies-literature

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Dynamic disorder in quasi-equilibrium enzymatic systems.

Chaudhury Srabanti S Igoshin Oleg A OA

PloS one 20100824 8

Conformations and catalytic rates of enzymes fluctuate over a wide range of timescales. Despite these fluctuations, there exist some limiting cases in which the enzymatic catalytic rate follows the macroscopic rate equation such as the Michaelis-Menten law. In this paper we investigate the applicability of macroscopic rate laws for fluctuating enzyme systems in which catalytic transitions are slower than ligand binding-dissociation reactions. In this quasi-equilibrium limit, for an arbitrary rea ...[more]

PMID: 20808776

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Project description:A growing amount of evidence over the last two decades points to the fact that many enzymes exhibit fluctuations in their catalytic activity, which are associated with conformational changes on a broad range of timescales. The experimental study of this phenomenon, termed dynamic disorder, has become possible thanks to advances in single-molecule enzymology measurement techniques, through which the catalytic activity of individual enzyme molecules can be tracked in time. The biological role and importance of these fluctuations in a system with a small number of enzymes, such as a living cell, have only recently started being explored. In this work, we examine a simple stochastic reaction system consisting of an inflowing substrate and an enzyme with a randomly fluctuating catalytic reaction rate that converts the substrate into an outflowing product. To describe analytically the effect of rate fluctuations on the average substrate abundance at steady state, we derive an explicit formula that connects the relative speed of enzymatic fluctuations with the mean substrate level. Under fairly general modelling assumptions, we demonstrate that the relative speed of rate fluctuations can have a dramatic effect on the mean substrate, and lead to large positive deviations from predictions based on the assumption of deterministic enzyme activity. Our results also establish an interesting connection between the amplification effect and the mixing properties of the Markov process describing the enzymatic activity fluctuations, which can be used to easily predict the fluctuation speed above which such deviations become negligible. As the techniques of single-molecule enzymology continuously evolve, it may soon be possible to study the stochastic phenomena due to enzymatic activity fluctuations within living cells. Our work can be used to formulate experimentally testable hypotheses regarding the nature and magnitude of these fluctuations, as well as their phenotypic consequences.

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Dynamic disorder in quasi-equilibrium enzymatic systems.

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Dynamic disorder in quasi-equilibrium enzymatic systems.

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