Editing Tocopherol (section)

==Forms==
[[Vitamin E]] exists in eight different forms, four tocopherols and four [[tocotrienol]]s. All feature a [[chromane]] ring, with a [[hydroxyl]] group that can donate a [[hydrogen]] atom to [[redox|reduce]] [[free radical]]s and a [[hydrophobic]] [[side chain]] that allows for penetration into [[biological membrane]]s. Both the tocopherols and [[tocotrienols]] occur in α (alpha), β (beta), γ (gamma), and δ (delta) forms, determined by the number and position of [[methyl]] groups on the chromanol ring.{{cn|date=December 2024}} <!--The alpha is most highly methylated (3 methyls on the chromanol ring) with the beta, gamma, and delta forms having two, one, and no methyl groups on the chromanol ring, respectively.-->

{| class="wikitable"
! Form || Structure
|-
| [[α-Tocopherol]] || [[File:Tocopherol, alpha-.svg|300px|class=skin-invert-image]]
|-
| [[β-Tocopherol]] ||  [[File:Beta-tocopherol.png|300px|class=skin-invert-image]]
|-
| [[γ-Tocopherol]] || [[File:Gamma-tocopherol.png|300px|class=skin-invert-image]]
|-
| [[δ-Tocopherol]]   ||  [[File:Delta-tocopherol.png|300px|class=skin-invert-image]]
|}

The [[tocotrienols]] have the same methyl structure at the ring and the same Greek-letter methyl notation, but differ from the analogous tocopherols by the presence of three [[double bond]]s in the hydrophobic side chain. The unsaturation of the tails gives [[tocotrienols]] only a single stereoisomeric carbon (and thus two possible isomers per structural formula, one of which occurs naturally), whereas tocopherols have three centers (and eight possible stereoisomers per structural formula, again, only one of which occurs naturally).

<!--[[File:VitE.png|450px|center]] -->
Each form has a different [[biological activity]].<ref name=fao1>{{cite report |author1=Food and Agriculture Organization |author2=World Health Organization |author1-link=Food and Agriculture Organization |author2-link=World Health Organization |date=2001 |title=Joint FAO/WHO Expert Consultation on Human Vitamin and Mineral Requirements |url=http://www.fao.org/3/Y2809E/y2809e00.htm |publisher=FAO Rome |location=Bangkok, Thailand |chapter= 9. Vitamin E |chapter-url=http://www.fao.org/3/Y2809E/y2809e0f.htm#bm15}}</ref><ref>{{cite journal | last1=Burton |first1= G. W. |last2= Ingold |first2= K. U. |title= Autoxidation of biological molecules. 1. Antioxidant activity of vitamin E and related chain-breaking phenolic antioxidants in vitro |journal= Journal of the American Chemical Society |year= 1981 |volume= 103 |issue= 21 |pages= 6472–6477 |doi=10.1021/ja00411a035 |bibcode= 1981JAChS.103.6472B }}</ref>
In general, the unnatural l-isomers of tocotrienols lack almost all vitamin activity, and half of the possible 8 isomers of the tocopherols (those with 2S chirality at the ring–tail junction) also lack vitamin activity. Of the stereoisomers that retain activity, increasing methylation, especially full methylation to the α-form, increases vitamin activity. In tocopherols, this is due to the higher binding energy of the α-tocopherol form of the vitamin to the tocopherol binding protein.

As a [[food additive]], tocopherol is labeled with these [[E number]]s: '''E306''' (tocopherol), '''E307''' (α-tocopherol), '''E308''' (γ-tocopherol), and '''E309''' (δ-tocopherol). All of these are approved in the US,<ref>{{cite web|url=https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm#ftnT |title=Listing of Food Additives Status Part II |website=[[Food and Drug Administration]] |access-date=2011-10-27 |url-status=dead |archive-url=https://web.archive.org/web/20111108002304/https://www.fda.gov/Food/FoodIngredientsPackaging/FoodAdditives/ucm191033.htm |archive-date=November 8, 2011 }}</ref> EU,<ref>{{cite web |url=http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |title=Current EU approved additives and their E Numbers |website=UK Food Standards Agency |access-date=2011-10-27 |url-status=live |archive-url=https://web.archive.org/web/20101007124435/http://www.food.gov.uk/safereating/chemsafe/additivesbranch/enumberlist |archive-date=2010-10-07 }}</ref> and Australia and New Zealand<ref>{{cite web |url=http://www.comlaw.gov.au/Details/F2011C00827 |title=Australia New Zealand Food Standards Code. Standard 1.2.4 – Labelling of ingredients |website=Federal Register of Legislation |publisher=Australian Government |date=8 September 2011 }}</ref> for use as antioxidants.

===α-Tocopherol===
{{Main|α-Tocopherol}}
α-Tocopherol is the form of vitamin E that is preferentially absorbed and accumulated in humans.<ref>{{cite journal | vauthors = Rigotti A | title = Absorption, transport, and tissue delivery of vitamin E | journal = Molecular Aspects of Medicine | volume = 28 | issue = 5–6 | pages = 423–436 | year = 2007 | pmid = 17320165 | doi = 10.1016/j.mam.2007.01.002 }}</ref> The measurement of "vitamin&nbsp;E" activity in [[international unit]]s (IU) was based on fertility enhancement by the prevention of miscarriages in pregnant rats relative to α-tocopherol.

Although the mono-methylated form ddd-γ-tocopherol is the most prevalent form of vitamin E in oils, there is evidence that rats can methylate this form to the preferred α-tocopherol, since several generations of rats retained α-tocopherol tissue levels, even when those generations were fed only γ-tocopherol through their lives.

There are three [[stereocenter]]s in α-tocopherol, so this is a [[Chirality (chemistry)|chiral]] molecule.<ref name=Jensen/> The eight [[Stereoisomerism|stereoisomers]] of α-tocopherol differ in the arrangement of groups around these stereocenters. In the image of ''RRR''-α-tocopherol below, all three stereocenters are in the ''R'' form. However, if the middle of the three stereocenters were changed (so the hydrogen was now pointing down and the [[methyl group]] pointing up), this would become the structure of ''RSR''-α-tocopherol. These stereoisomers also may be named in an alternative older nomenclature, where the stereocenters are either in the ''d'' or ''l'' form.<ref name=Traber/>

[[File:Alpha-Tocopherol Structural Formulae V.1.svg|thumb|250px|class=skin-invert-image|''RRR'' [[Stereoisomerism|stereoisomer]] of α-tocopherol, bonds around the [[stereocenter]]s are shown as dashed lines (pointing down) or wedges (pointing up).]]

1 IU of tocopherol is defined as {{frac|2|3}} milligrams of ''RRR''-α-tocopherol (formerly named d-α-tocopherol or sometimes ddd-α-tocopherol). 1&nbsp;IU is also defined as 1&nbsp;milligram of an equal mix of the eight stereoisomers, which is a [[racemic mixture]] called [[tocopheryl acetate|''all-rac''-α-tocopheryl acetate]]. This mix of stereoisomers is often called dl-α-tocopheryl acetate, even though it is more precisely {{chem name|dl,dl,dl-α-tocopheryl acetate}}). However, 1&nbsp;IU of this racemic mixture is not now considered equivalent to 1&nbsp;IU of natural (RRR) α-tocopherol, and the [[Institute of Medicine]] and the [[USDA]] now convert IU's of the racemic mixture to milligrams of equivalent RRR using 1&nbsp;IU racemic mixture = 0.45 "milligrams α-tocopherol".{{r|USDA-NDL|pp=20–21}}

===Tocotrienols===
{{Main|Tocotrienol}}
Tocotrienols also belong to the vitamin E family. Tocotrienols have four natural 2' d-isomers (they have a stereoisomeric carbon only at the 2' ring-tail position). The four tocotrienols (in order of decreasing methylation: d-α-, d-β-, d-γ-, and d-δ-tocotrienol) have structures corresponding to the four tocopherols, except with an unsaturated bond in each of the three [[isoprene]] units that form the hydrocarbon tail, whereas tocopherols have a saturated phytyl tail (the phytyl tail of tocopherols gives the possibility for 2 more stereoisomeric sites in these molecules that tocotrienols do not have). Tocotrienols have seen less research as compared to tocopherols.<ref>{{cite journal | vauthors = Sen CK, Khanna S, Roy S | title = Tocotrienols: Vitamin E beyond tocopherols | journal = Life Sciences | volume = 78 | issue = 18 | pages = 2088–2098 | date = March 2006 | pmid = 16458936 | pmc = 1790869 | doi = 10.1016/j.lfs.2005.12.001 }}</ref>