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Structure–Function Relationship Studies In Vitro Reveal Distinct and Specific Effects of Long‐Chain Metabolites of Vitamin E
Author(s) -
Schmölz Lisa,
Wallert Maria,
Rozzino Nicolò,
Cignarella Andrea,
Galli Francesco,
Glei Michael,
Werz Oliver,
Koeberle Andreas,
Birringer Marc,
Lorkowski Stefan
Publication year - 2017
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201700562
Subject(s) - biochemistry , cd36 , chemistry , nitric oxide , in vitro , vitamin e , function (biology) , biology , stereochemistry , receptor , antioxidant , microbiology and biotechnology , endocrinology
Scope Cytochrome‐dependent metabolism of vitamin E initially forms the long‐chain metabolites (LCM) 13′‐hydroxychromanols (13′‐OH) and 13′‐carboxychromanols (13′‐COOH), which occur in human blood. Little is known about their biological functions. Material and results A structure–activity relationship study using α‐ and δ‐tocopherol (TOH), their LCM (α‐13′‐OH, δ‐13′‐OH, α‐13′‐COOH, and δ‐13′‐COOH) and representatives of their substructures (α‐carboxyethylhydroxychromanol and pristanic acid) is performed to unravel critical structural elements of the LCM for biological activity. Prominent effects are mediated by α‐ and δ‐LCM, as scavenger receptor cluster of differentiation 36 (CD36) expression is induced in human THP‐1 macrophages and lipopolysaccharide‐stimulated inducible nitric oxide synthase (iNos) expression is inhibited in murine RAW264.7 macrophages, while the other molecules are less or not effective. Conclusion The LCM effects depend on the presence of the chromanol ring system and on the modification of the side‐chain but not on the substitution pattern of the chromanol ring. Therefore, it can be concluded that for mediation of effects by LCM the entire molecule is needed and that the effects are specific. We propose the LCM of the micronutrient vitamin E as a new class of regulatory metabolites, but further studies are needed to corroborate this hypothesis.