ABSTRACT
Natural forms of vitamin E are composed of eight membrane-soluble antioxidants, i.e., α-, β-, γ-, or δ-tocopherol (α-, β-, γ-, or δ-T) and α-, β-, γ-, or δ-tocotrienol (α-, β-, γ-, or δ-TE) (Figure 23.1). All these molecules have a chromanol ring and a 16-carbon hydrophobic side chain, which are, respectively, responsible for the potent antioxidant activity and lipophilic property. Tocopherols
23.1 Introduction .........................................................................................................................309 23.2 Overview of Absorption, Metabolism and Excretion of Vitamin E ................................... 310 23.3 Discovery of Urinary Metabolites of Vitamin E ................................................................ 312 23.4 Mechanistic Elucidation of the Metabolic Pathway ............................................................ 314
23.4.1 Elucidation of the Metabolic Pathway in HepG2 Cells ........................................ 314 23.4.2 Novel Discovery of Sulfated Long-Chain Carboxychromanols ........................... 315
23.5 Measurement of CEHCs in Animals and Humans ............................................................. 317 23.5.1 Methods for Detection of Metabolites .................................................................. 317 23.5.2 Metabolites in the Plasma and Tissues ................................................................. 319
23.6 Regulation of Metabolism ................................................................................................... 319 23.6.1 Alpha-Tocopherol Transfer Protein ...................................................................... 319 23.6.2 Tocopherol ω-Hydroxylase ................................................................................... 320 23.6.3 Alpha-T Regulates the Metabolism of Other Forms of Vitamin E and Drugs
by Modulating the Expression of Cytochrome P-450 and p-Glycoprotein .......... 321 23.6.4 The Role of Sulfation ............................................................................................ 321
23.7 Novel Functions of Vitamin E Metabolites ........................................................................ 322 23.7.1 Natriuretic Activity of γ-CEHC ............................................................................ 322 23.7.2 Protection Against Nephrotoxicity by γ-CEHC ................................................... 322 23.7.3 Anti-Inammatory Activity of CEHC: Inhibition of Cyclooxygenase-
Catalyzed Proinammatory Eicosanoid Formation ............................................. 322 23.7.4 Long-Chain Carboxychromanols as Potent Inhibitors of Cyclooxygenases ........ 323 23.7.5 Sulfated Compounds .............................................................................................324
