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Inhibition mechanism of 3-hydroxy-3-methyl-glutaryl-CoA reductase by tocotrienol-rich rice bran fraction optimally extracted with ultrasonic energy.
- Source :
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International journal of biological macromolecules [Int J Biol Macromol] 2020 Dec 01; Vol. 164, pp. 1328-1341. Date of Electronic Publication: 2020 Jul 26. - Publication Year :
- 2020
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Abstract
- Tocotrienols (T3) are vitamin E components that inhibit 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGR), a primary target for cholesterol management. T3 was extracted from rice bran (RBE) using ultrasonic energy keeping solute: solvent ratio, power and time on specific energy and T3 concentration as responses as per Box-Behnken Design. The lowest specific energy (52.38 ± 0.14 J mL <superscript>-1</superscript> ) uptake by the sample was most effective in enhancing the concentration of T3 in RBE (199.34 ± 0.63 μg mL <superscript>-1</superscript> ). In vitro HMGR kinetics and in silico binding interactions of the identified α-, δ- and γ-T3 fractions were studied. Enzyme kinetic studies revealed an uncompetitive mode of inhibition by α-T3, γ-T3, and RBE and a mixed mode of inhibition for δ-T3. γ-T3 showed lowest IC <subscript>50</subscript> concentration (11.33 μg mL <superscript>-1</superscript> ) followed by α-T3 (16.73 μg mL <superscript>-1</superscript> ), RBE (20.45 μg mL <superscript>-1</superscript> ) and δ-T3 (23.16 μg mL <superscript>-1</superscript> ). Molecular docking studies highlighted the hydrogen bonding of δ-T3 with Gln766 and α- and γ-T3 with Met655 and Val805 amino acid residues at the NADPH binding site of HMGR. Results indicate the potential use of T3 enriched RBE optimally extracted using ultrasound as potent HMGR inhibitor.<br />Competing Interests: Declaration of competing interest The authors declare no conflict of interest.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)
- Subjects :
- Binding Sites
Cholesterol
Chromatography, High Pressure Liquid
Fatty Acids, Nonesterified chemistry
Imaging, Three-Dimensional
Inhibitory Concentration 50
Kinetics
Ligands
Molecular Conformation
Molecular Docking Simulation
Oxidoreductases
Peroxides
Protein Binding
Solvents
Sonication
Vitamin E
Dietary Fiber metabolism
Hydroxymethylglutaryl-CoA Reductase Inhibitors chemistry
Hydroxymethylglutaryl-CoA-Reductases, NADP-dependent chemistry
Oryza chemistry
Tocotrienols chemistry
Ultrasonics
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 164
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 32726652
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2020.07.196