Please use this identifier to cite or link to this item: https://hdl.handle.net/11000/30661

The extra virgin olive oil phenolic oleacein is a dual substrate-inhibitor of catechol-O-methyltransferase


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Title:
The extra virgin olive oil phenolic oleacein is a dual substrate-inhibitor of catechol-O-methyltransferase
Authors:
Cuyàs, Elisabet  
Verdura, Sara  
Lozano Sánchez, Jesús  
Viciano, Ignacio  
Llorach-Pares, Laura  
Nonell-Canals, Alfons  
Bosch-Barrera, Joaquim  
Brunet, Joan  
segura Carretero, Antonio  
Sanchez-Martinez, Melchor  
Encinar, José Antonio  
MENÉNDEZ MENÉNDEZ, JAVIER ABEL  
Editor:
Elsevier
Department:
Departamentos de la UMH::Bioquímica y Biología Molecular
Issue Date:
2019-03-26
URI:
https://hdl.handle.net/11000/30661
Abstract:
Catechol-containing polyphenols present in coffee and tea, while serving as excellent substrates for catechol-Omethyltransferase (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.
Keywords/Subjects:
extra virgin olive oil
polyphenols
secoiridoids
oleacein
COMT
cancer
Knowledge area:
CDU: Ciencias puras y naturales: Biología: Bioquímica. Biología molecular. Biofísica
Type of document:
application/pdf
Access rights:
info:eu-repo/semantics/closedAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
DOI:
https:// doi.org/10.1016/j.fct.2019.03.049
Appears in Collections:
Artículos Bioquímica y Biología Molecular



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