Classification of difference between inhibition constants of an inhibitor to facilitate identifying the inhibition type

Yang, Xiaolan; Du, Zhiyin; Pu, Jun; Zhao, Hua; Chen, Hong; Liu, Yin; Li, Zhirong; Cheng, Zhenli; Zhong, Huansi; Liao, Fei

doi:10.3109/14756366.2011.645240

Cited by 45 publications

(37 citation statements)

References 23 publications

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“…K ik / K iv ratio was calculated according to Yang et al. 21 a p -Nitrophenyl phosphate ( p NPP) as substrate. b p- Nitrophenyl glucopyranoside ( p NPG) as substrate.…”

Section: Resultsmentioning

confidence: 99%

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Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa

Song

Uddin

Jin

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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Protein tyrosine phosphatase 1B (PTP1B) and α-glucosidase are important targets to treat obesity and diabetes, due to their deep correlation with insulin and leptin signalling, and glucose regulation. The methanol extract of Paulownia tomentosa fruits showed potent inhibition against both enzymes. Purification of this extract led to eight geranylated flavonoids (1–8) displaying dual inhibition of PTP1B and α-glucosidase. The isolated compounds were identified as flavanones (1–5) and dihydroflavonols (6–8). Inhibitory potencies of these compounds varied accordingly, but most of the compounds were highly effective against PTP1B (IC50 = 1.9–8.2 μM) than α-glucosidase (IC50 = 2.2–78.9 μM). Mimulone (1) was the most effective against PTP1B with IC50 = 1.9 μM, whereas 6-geranyl-3,3′,5,5′,7-pentahydroxy-4′-methoxyflavane (8) displayed potent inhibition against α-glucosidase (IC50 = 2.2 μM). All inhibitors showed mixed type Ι inhibition toward PTP1B, and were noncompetitive inhibitors of α-glucosidase. This mixed type behavior against PTP1B was fully demonstrated by showing a decrease in Vmax, an increase of Km, and Kik/Kiv ratio ranging between 2.66 and 3.69.

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“…K ik / K iv ratio was calculated according to Yang et al. 21 a p -Nitrophenyl phosphate ( p NPP) as substrate. b p- Nitrophenyl glucopyranoside ( p NPG) as substrate.…”

Section: Resultsmentioning

confidence: 99%

“…Similarly K m and V max were derived from Lineweaver–Burk plots. K ik and K iv rate constants were calculated according to Equations (4) and (5) proposed by Yang’s method 21 . While Excel was used for linear regression analysis.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa

Song

Uddin

Jin

et al. 2017

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…To further determine whether CRA was an uncompetitive inhibitor, the data were analyzed following Yang's method . The difference between K ik and K iv was quantized as the ratio of the larger one to the smaller one.…”

Section: Resultsmentioning

confidence: 99%

“…The values of the Michaelis–Menten constant ( K m ) and the maximum velocity ( V max ) were ascertained by the Lineweaver–Burk plots in Eqn (1) . The values of new kinetic constants K ik and K iv , which reflected the changes in K m and V max against inhibitor concentrations, were derived from Eqns (2) and (3) respectively according to Yang's method:

\frac{1}{V} = \frac{K_{m}}{V_{\max}} \frac{1}{([], S)} + \frac{1}{V_{\max}}

\frac{1}{K_{m}} = \frac{1}{K_{normalm, 0}} \times (1 + \frac{([], I)}{K_{ik}})

\frac{1}{V_{\max}} = \frac{1}{V_{normalmax, 0}} \times (1 + \frac{([], I)}{K_{iv}})

where K m,0 and V max,0 represent the Michaelis–Menten constant and the maximum velocity of the enzyme without any inhibitor, respectively. [ S ] and [ I ] represent the concentrations of the substrate pNPG and inhibitor CRA, respectively.…”

Section: Methodsmentioning

confidence: 99%

“…To further determine whether CRA was an uncompetitive inhibitor, the data were analyzed following Yang's method. 28 The difference between K ik and K iv was quantized as the ratio of the larger one to the smaller one. If this ratio is below 2.0 this suggests that the inhibitor is uncompetitive; if it is over 5.0 this implies noncompetitive or competitive and from 2.0 to 5.0 indicates a mixed-type inhibitor.…”

Section: Type Of -Glucosidase Inhibitionmentioning

confidence: 99%

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Inhibitory effect of corosolic acid on α‐glucosidase: kinetics, interaction mechanism, and molecular simulation

Pan

et al. 2019

J Sci Food Agric

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BACKGROUND The suppression of α‐glucosidase activity to retard glucose absorption is an important therapy for type‐2 diabetes. Corosolic acid (CRA) is a potential antidiabetic component in many plant‐based foods and herbs. In this study, the interplay mechanism between α‐glucosidase and corosolic acid was investigated by several methods, including three‐dimensional fluorescence spectra, circular dichroism spectra, and molecular simulation. RESULTS Corosolic acid significantly inhibited α‐glucosidase reversibly in an uncompetitive manner and its IC50 value was 1.35 × 10−5 mol L−1. A combination of CRA with myricetin exerted a weak synergy against α‐glucosidase. The intrinsic fluorescence of α‐glucosidase was quenched via a static quenching course and the binding constant was 3.47 × 103 L mol−1 at 298 K. The binding of CRA to α‐glucosidase was mainly driven by hydrophobic forces and resulted in a partial extension of the protein polypeptide chain with a loss of α‐helix content. The molecular simulation illustrated that CRA bound to the entrance part of the active center of α‐glucosidase and interacted with the amino acid residues Ser157, Arg442, Phe303, Arg315, Tyr158, and Gln353, which could hinder the release of substrate and catalytic reaction product, eventually suppressing the catalytic activity of α‐glucosidase. CONCLUSIONS These results may suggest new insights into corosolic acid from food sources as a potential α‐glucosidase inhibitor that could better control diabetes. © 2019 Society of Chemical Industry

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Quinic acid as an inhibitor of α‐glucosidase activity, nonenzymatic glycosylation, and glucose transport in Caco‐2 cells

Han,

Wang,

Sun

et al. 2024

Food Frontiers

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Hyperglycemia and diabetes are common metabolic disorders. It is considered a safe and effective strategy to screen active ingredients from food and herbs for controlling blood sugar levels. Quinic acid (QA) is a natural polyphenolic acid with various health‐promoting properties. In this study, QA was found to exhibit a potent inhibitory effect on α‐glucosidase activity, with a half maximal inhibitory concentration (IC50) of 5.46 mM. This inhibitory property surpassed that of three common organic acids including gallic acid, malic acid, and citric acid. A combination of 25% acarbose (0.5 mM) and 75% QA (5 mM) (v/v) exhibited synergistic inhibition of α‐glucosidase activity. Enzyme kinetics, fluorescence spectra, and molecular docking analyses indicated that QA acted as an uncompetitive inhibitor of α‐glucosidase, with hydrogen bonds playing a key role in the intermolecular interactions. Moreover, QA was found to effectively inhibit three major nonenzymatic glycation products including advanced glycosylation end products (AGEs), fructosamine, and α‐dicarbonyl in a dose‐dependent manner, outperforming the positive control aminoguanidine (AG) within the tested concentration range. Utilizing a Caco‐2 cell model, QA demonstrated the ability to inhibit the transmembrane absorption of glucose. This study highlighted QA as a promising food functional factor that had been overlooked in the past, offering potential benefits in improving hyperglycemia, diabetes, and associated complications through the inhibition of α‐glucosidase, nonenzymatic glycosylation, and glucose uptake.

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Classification of difference between inhibition constants of an inhibitor to facilitate identifying the inhibition type

Abstract: (2013) Classification of difference between inhibition constants of an inhibitor to facilitate identifying the inhibition type, Journal of Enzyme Inhibition and

Cited by 45 publications

References 23 publications

Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa

Inhibition of protein tyrosine phosphatase (PTP1B) and α-glucosidase by geranylated flavonoids from Paulownia tomentosa

Inhibitory effect of corosolic acid on α‐glucosidase: kinetics, interaction mechanism, and molecular simulation

Quinic acid as an inhibitor of α‐glucosidase activity, nonenzymatic glycosylation, and glucose transport in Caco‐2 cells

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