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The extra virgin olive oil phenolic oleacein is a dual substrate-inhibitor of catechol-O-methyltransferase
- Source :
- Food and Chemical Toxicology. 128:35-45
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Catechol-containing polyphenols present in coffee and tea, while serving as excellent substrates for catechol-O-methyltransferase (COMT)-catalyzed O-methylation, can also operate as COMT inhibitors. However, little is known about the relationship between COMT and the characteristic phenolics present in extra virgin olive oil (EVOO). We here selected the EVOO dihydroxy-phenol oleacein for a computational study of COMT-driven methylation using classic molecular docking/molecular dynamics simulations and hybrid quantum mechanical/molecular mechanics, which were supported by in vitro activity studies using human COMT. Oleacein could be superimposed onto the catechol-binding site of COMT, maintaining the interactions with the atomic positions involved in methyl transfer from the S-adenosyl-L-methionine cofactor. The transition state structure for the meta-methylation in the O5 position of the oleacein benzenediol moiety was predicted to occur preferentially. Enzyme analysis of the conversion ratio of catechol to O-alkylated guaiacol confirmed the inhibitory effect of oleacein on human COMT, which remained unaltered when tested against the protein version encoded by the functional Val158Met polymorphism of the COMT gene. Our study provides a theoretical determination of how EVOO dihydroxy-phenols can be metabolized via COMT. The ability of oleacein to inhibit COMT adds a new dimension to the physiological and therapeutic utility of EVOO secoiridoids.
- Subjects :
- Catechols
Catechol O-Methyltransferase
Toxicology
Methylation
behavioral disciplines and activities
Molecular mechanics
Cofactor
Substrate Specificity
03 medical and health sciences
chemistry.chemical_compound
Methionine
0404 agricultural biotechnology
Phenols
mental disorders
Humans
Olive Oil
030304 developmental biology
chemistry.chemical_classification
Aldehydes
0303 health sciences
Catechol
Polymorphism, Genetic
Catechol-O-methyl transferase
biology
fungi
Catechol O-Methyltransferase Inhibitors
Valine
04 agricultural and veterinary sciences
General Medicine
040401 food science
Molecular Docking Simulation
Enzyme
Benzenediol
nervous system
chemistry
Biochemistry
Polyphenol
biology.protein
Guaiacol
Food Science
Subjects
Details
- ISSN :
- 02786915
- Volume :
- 128
- Database :
- OpenAIRE
- Journal :
- Food and Chemical Toxicology
- Accession number :
- edsair.doi.dedup.....17f65d9eb040b6a0918459c52db17782