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A graphical method for determining inhibition parameters for partial and complete inhibitors.

ABSTRACT: A new simple graphical method is described for the determination of inhibition type and kinetic parameters of an enzyme reaction without any replot. The method consists of plotting experimental data as v/(vo--v) versus the reciprocal of the inhibitor concentration at different substrate concentrations, where v and vo represent the velocity in the presence and in the absence of the inhibitor respectively with a given concentration of the substrate. Partial inhibition gives straight lines that converge on the abscissa at a point away from the origin, whereas complete inhibition gives lines that go through the origin. The inhibition constants of enzymes and the reaction rate constant of the enzyme-substrate-inhibitor complex can be calculated from the abscissa and ordinate intercepts of the plot. The relationship between the slope of the plot and the substrate concentration shows characteristic features depending on the inhibition type: for partial competitive inhibition, the straight line converging on the abscissa at--Ks, the dissociation constant of the enzyme-substrate complex; for non-competitive inhibition, a constant slope independent of the substrate concentration; for uncompetitive inhibition, a hyperbola decreasing with the increase in the substrate concentration; for mixed-type inhibition, a hyperbola increasing with the increase in the substrate concentration. The properties of the replot are useful in confirmation of the inhibition mechanism.

SUBMITTER: Yoshino M

PROVIDER: S-EPMC1148622 | biostudies-other | 1987 Dec

REPOSITORIES: biostudies-other

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Project description:BackgroundRenin-angiotensin system inhibitors (RASi) are not re-initiated for almost a quarter of patients who suffered acute kidney injury 6 months after discharge. This discontinuation might be partly explained by the nephrotoxicity of these medications, yet they remain of benefit, especially for patients with heart failure.ObjectiveTo determine the factors deemed by clinicians to influence RASi re-initiation and set threshold values for important safety parameters.DesignThree-round modified online Delphi survey.SettingThe study was conducted in Quebec, Canada.ParticipantsTwenty clinicians from nephrology, intensive care medicine, and internal medicine.MeasurementsThe factors' importance was rated on 4-point Likert-type scale, ranging from "not important" to "very important" by the panelists.MethodsWe conducted a brief literature review to uncover possible influencing factors followed by a 3-round modified Delphi survey to establish a consensus on the importance of these factors.ResultsWe recruited 20 clinicians (7 nephrologists, 3 internists, and 10 intensive care physicians). We created a list of 25 factors, 15 of which met consensus. Eleven of these factors, including serum creatinine, glomerular filtration rate, and acute kidney injury (AKI) stage, were deemed as important while 4, such as responsibility ambiguity and absence of feedback, were deemed as not important. The majority of the 10 factors which did not meet consensus were related to the clinical setting, such as a pharmacist follow-up and the required time to ensure optimal RASi re-initiation.LimitationsQuebec clinicians' agreement might not reflect the opinion of the rest of Canada. The survey measures clinicians' belief rather than their actual practice.ConclusionRenin-angiotensin system inhibitors re-initiation is a rather complex concept which encompasses several factors. Our research uncovered some of these factors which may be used to develop guidelines on optimal RASi re-initiation.

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A graphical method for determining inhibition parameters for partial and complete inhibitors.

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