The nomenclature for vitamin E can be confusing because the term vitamin E refers to a group of closely related compounds that share biological activity. Vitamin E is therefore a group of vitamers, the main subdivisions of which are α-, β-, γ- and δ-tocopherol and α-, β-, γ- and δ-tocotrienol. These vitamin E vitamers all possess a chromanol head and a phytyl tail made of isoprenoid units, but vary slightly in their functional groups or bonding pattern. The tocopherols all possess the same saturated phytyl tail, but differ in the number and location of the methyl groups on their chromanol head. The tocotrienols possess the same methylation patterns on their chromanol head as their equivalently named tocopherol, but possess an unsaturated phytyl tail which contains 3 unconjugated double bonds. This gives the tocotrienols a distinct curvature to their tails, which alters their biological properties considerably.
Figure 1. The eight vitamers of vitamin E. Each vitamer has a chromanol head and a phytyl tail. The methylation pattern on the chromanol head gives the α-, β-, γ- or δ-designation. The tocopherols possess a saturated phytyl tail, whereas the tocotrienols possess an unsaturated phytyl tail.
Each of the eight vitamers also possesses stereo-centres. In the case of the tocopherol, this allows the molecule to form eight possible stereoisomers, whereas the tocotrienols can only form two as they do not possess the two chiral centres on their phytyl tails (figure 2). Each chiral centre can have two orientation of their bonding groups, and these orientations are designated R (dextral) and S (sinistral) depending on whether they rotate plain polarised light to the right or left, respectively. Because there are 3 chiral centres and each can possess one of two orientations (R or S) there are eight possible combination of stereoisomers for the tocopherols, RRR, RRS, RSR, SRR, SSS, RSS, SRS and RSS. In nature vitamin E is always in the RRR form, and this is also referred to as the D– form. The compound D-α-tocopherol (RRR- α-tocopherol) is designated a biological activity of 100%.
Figure 2. The eight stereoisomers of α-tocopherol. Each tocopherol vitamer of vitamin E possesses similar stereoisomerism because they all possess the same saturated phytyl tails. However the unsaturated phytyl tail of the tocotrienols removes two of the stereoisomeric sites and so only two stereoisomers of the tocotrienols (R and S) exist.
Synthetically produced vitamin E contains a random mixture (~12.5 %) of each of the eight stereoisomers, and this is referred to as a racemic mixture. In the case of synthetic α-tocopherol, the compound is named all-rac-α-tocopherol. Because synthetic vitamin E contains both sinistral (L) and dextral (D) stereoisomers it is also referred to as dl-α-tocopherol. Vitamin E is absorbed into chylomicrons and transferred to high density lipoproteins (HDL) during chylomicron depletion. The HDL particles are taken up by the liver and vitamin E is transferred to the very low density lipoprotein particles for distribution to peripheral tissue by the action of the tocopherol transport protein (TTP). This protein preferentially recognises the natural (RRR) stereoisomer. The 2R stereoisomers retain some affinity for the TTP, but the 2S stereoisomers do not. As a result the synthetic all-rac-α-tocopherol (dl-α-tocopherol) only has around half the biological activity of the natural RRR form.
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