Long-Chain Metabolites of Vitamin E: Metabolic Activation as a General Concept for Lipid-Soluble Vitamins?

Martin Schubert, Stefan Kluge, Lisa Schmölz, Maria Wallert, Francesco Galli, Marc Birringer, Stefan Lorkowski, Martin Schubert, Stefan Kluge, Lisa Schmölz, Maria Wallert, Francesco Galli, Marc Birringer, Stefan Lorkowski

Abstract

Vitamins E, A, D and K comprise the class of lipid-soluble vitamins. For vitamins A and D, a metabolic conversion of precursors to active metabolites has already been described. During the metabolism of vitamin E, the long-chain metabolites (LCMs) 13'-hydroxychromanol (13'-OH) and 13'-carboxychromanol (13'-COOH) are formed by oxidative modification of the side-chain. The occurrence of these metabolites in human serum indicates a physiological relevance. Indeed, effects of the LCMs on lipid metabolism, apoptosis, proliferation and inflammatory actions as well as tocopherol and xenobiotic metabolism have been shown. Interestingly, there are several parallels between the actions of the LCMs of vitamin E and the active metabolites of vitamin A and D. The recent findings that the LCMs exert effects different from that of their precursors support their putative role as regulatory metabolites. Hence, it could be proposed that the mode of action of the LCMs might be mediated by a mechanism similar to vitamin A and D metabolites. If the physiological relevance and this concept of action of the LCMs can be confirmed, a general concept of activation of lipid-soluble vitamins via their metabolites might be deduced.

Keywords: 13′-carboxychromanol (13′-COOH); 13′-hydroxychromanol (13′-OH); biological activity; long-chain metabolites of vitamin E; vitamin E; vitamin E metabolism.

Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Metabolism of vitamin E. The metabolism of vitamin E is initiated by a terminal ω-hydroxylation of the side-chain via CYP4F2 and CYP3A4. The resulting hydroxychromanol is further modified by ω-oxidation, resulting in the formation of carboxychromanol, possibly by alcohol and aldehyde dehydrogenases. As a consequence, the metabolite can be subjected to β-oxidation. Five cycles of β-oxidation lead to the formation of the short-chain metabolite CEHC. However, this review focuses on the LCMs 13′-OH and 13′-COOH as these molecules have been synthesized in sufficient amounts for in vitro and in vivo investigations. The following abbreviations are used: ADH, alcohol dehydrogenase; ALDH, aldehyde dehydrogenase; CDMDHC, carboxydimethyldecylhydroxychromanol; CDMOHC, carboxymethyloctylhydroxychromanol; CDMHHC, carboxymethylhexylhydroxychromanol; CMBHC, carboxymethylbutylhydroxychromanol; CEHC, carboxyethylhydroxychromanol.
Figure 2
Figure 2
Reported biological functions of the LCMs of vitamin E.

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