Structure–Function Relationship Studies In Vitro Reveal Distinct and Specific Effects of Long‐Chain Metabolites of Vitamin E. Issue 12 (3rd November 2017)

• Record Type: Journal Article
• Authors: Schmölz, Lisa; Wallert, Maria; Rozzino, Nicolò; Cignarella, Andrea; Galli, Francesco; Glei, Michael; Werz, Oliver; Koeberle, Andreas; Birringer, Marc; Lorkowski, Stefan
• Is Part Of: Molecular nutrition & food research. Volume 61:Issue 12(2017)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2017-11-03
• Subjects: α‐13′‐OH -- α‐13′‐hydroxychromanol -- α‐13′‐COOH -- α‐13′‐carboxychromanol -- long‐chain metabolites of vitamin E; Food -- Biotechnology -- Periodicals; Food -- Microbiology -- Periodicals; Nutrition -- Periodicals; Food -- Toxicology -- Periodicals; Nutrition -- Periodicals; Food Microbiology -- Periodicals; Food Technology -- Periodicals; Molecular Biology -- Periodicals; 664.0705
• DOI: 10.1002/mnfr.201700562
• Languages: English
• ISSNs: 1613-4125

Abstract

Abstract : 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. Abstract : Cytochrome‐dependent metabolism of vitamin E initially forms long‐chain metabolites (LCM) 13′‐hydroxychromanols (13′‐OH) and 13′‐carboxychromanols (13′‐COOH). A structure–activity relationship study using α‐ and δ‐tocopherol, their 13′‐LCM and representatives of their substructures (α‐carboxyethylhydroxychromanol and pristanic acid) is performed to unravel structural elements required for biological activity. The LCM effects depend on the presence of the chromanol system and the modification of the side‐chain but not on the substitution pattern of the chromanol ring. It can be concluded that for effects the entire LCM molecule is needed and that the effects are specific.