439 JOURNAL OF BIOSCIENCE AND BIOENGINEERING © 2007, The Society for Biotechnology, Japan Vol. 104, No. 6, 439–445. 2007 DOI: 10.1263/jbb.104.439 REVIEW Chemical Reactivities and Physical Effects in Comparison between Tocopherols and Tocotrienols: Physiological Significance and Prospects as Antioxidants Yasukazu Yoshida, 1 Yoshiro Saito, 1 Leslie Sargent Jones, 2 and Yasushi Shigeri 1 * Human Stress Signal Research Center (HSSRC), National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan 1 and Department of Pharmacology, Physiology, & Neuroscience, University of South Carolina, Columbia, SC 29208, USA 2 Received 24 August 2007/Accepted 25 October 2007 Vitamin E is a generic term for all tocopherol and tocotrienol derivatives. The most abundant and active form of vitamin E isoforms in vivo is α-tocopherol, but recently the roles of other forms of vitamin E have received renewed attention. In this review, we summarize the differences among α-, β-, γ-, δ-tocopherols and tocotrienols specifically regarding the following points; (i) their radical- scavenging efficacies and chemical reactivity with metal ions in solution, (ii) their physical effects at the liposomal membrane interior, and (iii) their protective effects against cell toxicity. Moreover, the physiological significance and future prospects for using vitamin E, especially tocotrienols, for the prevention and treatment of disease are discussed. [Key words: antioxidant, free radical, lipid peroxidation, tocopherol, tocotrienol] Vitamin E is a generic term for all tocopherol (T) and tocotrienol (T3) derivatives. Although other forms of vita- min E, desmethyl and didesmethyl tocotrienols, monoenol, and marine-derived tocopherol, were recently discovered, α-, β-, γ-, and δ-T and T3 are the major forms (Fig. 1). Toco- pherols have a phytyl chain, while tocotrienols have a simi- lar chain but with three double bonds at positions 3′, 7′, and 11′. Both tocopherols and tocotrienols have four isomers, designated as α-, β-, γ-, and δ-, which differ by the number and position of methyl groups on the chroman ring (Fig. 1). α-Tocopherol is the major vitamin E in vivo and exerts the most potent biological activity. Tocopherols are present in polyunsaturated vegetable oils and in the germ of cereal seeds, whereas tocotrienols are found in the aleurone and subaleurone layers of cereal seeds and in palm oils. Chemi- cally, T and T3 are closely related, however, it has been ob- served that they have widely varying degrees of biological effectiveness (1–13). In this review, the focus is on chemical and physical effects on the antioxidant actions of T and T3 in solutions and membranes. CHEMICAL REACTIVITY The oxidation of biological molecules by reactive oxygen and nitrogen species such as lipids, proteins, and DNA is thought to be responsible for the development of numerous pathological events such as cancer and aging (14, 15). Chain- breaking antioxidants such as vitamin E, suppress oxidation and protect biological molecules and tissues from oxidative damage (16–19). As a consequence, the role of antioxidants has received a great deal of attention. The first trials to in- * Corresponding author. e-mail: yasushi.shigeri@aist.go.jp phone: +81-(0)3-3599-8138 fax: +81-(0)3-5530-2064 FIG. 1. Chemical structures of vitamin E. Note that the R substitu- ent determines whether the isomers are tocopherols or tocotrienols. Monoenol or marine-derived tocopherol (MDT) may be formed with the indicated additions at the R position of the α-isomer. The des- methyl and didesmethyl tocotrienol molecules are shown individually due to their differing chroman ring structure.