Comparing enzyme activity modifier equations through the development of global data fitting templates in Excel
A peer-reviewed article of this Preprint also exists.
Author and article information
Abstract
The classical way of defining enzyme inhibition has obscured the distinction between inhibitory effect and the inhibitor binding constant. This article examines the relationship between the simple binding curve used to define biomolecular interactions and the standard inhibitory term (1+([I]/Ki)). By understanding how this term relates to binding curves which are ubiquitously used to describe biological processes, a modifier equation which distinguishes between inhibitor binding and the inhibitory effect, is examined. This modifier equation which can describe both activation and inhibition is compared to standard inhibitory equations with the development of global data fitting templates in Excel and via the global fitting of these equations to simulated and previously published datasets. In both cases, this modifier equation was able to match or outperform the other equations by providing superior fits to the datasets. The ability of this single equation to outperform the other equations suggests an over-complication of the field. This equation and the template developed in this article should prove to be useful tools in the study of enzyme inhibition and activation.
Cite this as
2018. Comparing enzyme activity modifier equations through the development of global data fitting templates in Excel. PeerJ Preprints 6:e3094v2 https://doi.org/10.7287/peerj.preprints.3094v2note This preprint is not peer-reviewed. You may wish to reference the subsequent peer-reviewed version of this article.
Author comment
The paper has been expanded to include simulated data, more detailed instruction on the use of the templates, a derivation of the term for substrate modification described by the modifier equation and tables comparing the ability of each equation to fit the presented datasets.
Sections
Supplemental Information
S4 Gen5 Biotek inhibition of β-galactosidase by β-D-thiogalactopyranoside
S5 E. characias leave aq extract tyrosinase inhibitory activity
S6 E. characias leave EtOH extract tyrosinase inhibitory activity
S8 modifier template alanine inhibition of glutamine synthase
S9 Partial inhibition template alanine inhibition of glutamine synthase
S10 modifier template inosine nucleosidase inhibition by adenine
S11 partial inhibition template inosine nucleosidase inhibition by adenine
S12 modifier template adenosine monophosphate inhibition of alcohol dehydrogenase
S13 partial inhibition template adenosine monophosphate inhibition of alcohol dehydrogenase
S14 modifier template adenosine triphosphate inhibition of mevalonate diphosphate decarboxylase
S15 partial inhibition template adenosine triphosphate inhibition of mevalonate diphosphate decarboxylase
S16 partial inhibition template Gen5 Biotek inhibition of β-galactosidase by β-D-thiogalactopyranoside
S17 partial inhibition E. characias leave aq extract tyrosinase inhibitory activity
S18 partial inhibition template E. characias leave EtOH extract tyrosinase
S22 partial inhibition template competitive inhibition
Additional Information
Competing Interests
The authors declare that they have no competing interests.
Author Contributions
Ryan Walsh conceived and designed the experiments, analyzed the data, contributed reagents/materials/analysis tools, prepared figures and/or tables, authored or reviewed drafts of the paper, approved the final draft.
Data Deposition
The following information was supplied regarding data availability:
Supplementary files consist of Excel templates for analyzing enzyme kinetic data, detailed instructions for their use, derivation of one of the equations and the application of these templates to previously published data
S1 derivation
S2 modifier template
S3 template data fitting
S4 Gen5 Biotek inhibition of β-galactosidase by β-D-thiogalactopyranoside
S5 E. characias leave aq extract tyrosinase inhibitory activity
S6 E. characias leave EtOH extract tyrosinase inhibitory activity
S7 partial inhibition template
S8 modifier template alanine inhibition of glutamine synthase
S9 Partial inhibition template alanine inhibition of glutamine synthase
S10 modifier template inosine nucleosidase inhibition by adenine
S11 partial inhibition template inosine nucleosidase inhibition by adenine
S12 modifier template adenosine monophosphate inhibition of alcohol dehydrogenase
S13 partial inhibition template adenosine monophosphate inhibition of alcohol dehydrogenase
S14 modifier template adenosine triphosphate inhibition of mevalonate diphosphate decarboxylase
S15 partial inhibition template adenosine triphosphate inhibition of mevalonate diphosphate decarboxylase
S16 partial inhibition template Gen5 Biotek inhibition of β-galactosidase by β-D-thiogalactopyranoside
S17 partial inhibition E. characias leave aq extract tyrosinase inhibitory activity
S18 partial inhibition template E. characias leave EtOH extract tyrosinase
S19 noncompetitive inhibition
S20 partial inhibition template noncompetitive
S21 Competitive inhibition
S22 partial inhibition template competitive inhibition
S23 Uncompetitive inhibition
S24 partial inhibition template uncompetitive
S25 mixed noncompetitive inhibition
S26 partial inhibition template mixed noncomp
S27 Activation
S28 partial inhibition template activation
Funding
The authors received no funding for this work.
