α-Tocopherol
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| Names | |
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| Preferred IUPAC name
(2R)-2,5,7,8-Tetramethyl-2-[(4R,8R)-4,8,12-trimethyltridecyl]-3,4-dihydro-2H-1-benzopyran-6-ol | |
| Identifiers | |
3D model (JSmol) |
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| ChEBI | |
| ChEMBL | |
| ChemSpider | |
| DrugBank | |
| ECHA InfoCard | 100.000.375 |
| EC Number |
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| E number | E307a (antioxidants, ...) |
PubChem CID |
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| UNII | |
CompTox Dashboard (EPA) |
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| Properties | |
| C29H50O2 | |
| Molar mass | 430.71 g/mol |
| Appearance | yellow-brown viscous liquid |
| Density | 0.950 g/cm3 |
| Melting point | 2.5 to 3.5 °C (36.5 to 38.3 °F; 275.6 to 276.6 K) |
| Boiling point | 200 to 220 °C (392 to 428 °F; 473 to 493 K) at 0.1 mmHg |
| insoluble | |
| Solubility | soluble in alcohol, ether, acetone, oils |
| Pharmacology | |
| A11HA03 (WHO) | |
| Hazards | |
| NFPA 704 (fire diamond) | |
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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α-Tocopherol (alpha-tocopherol) is a type of vitamin E.[2][3]
It is found most in the membrane's non-raft domains, associated with omega-3 and 6 fatty acids, to partially prevent oxidation.[4] The most prevalent form, α-tocopherol, is involved in molecular, cellular, biochemical processes closely related to overall lipoprotein and lipid homeostasis.[2] Compared to the others, α-tocopherol is preferentially absorbed and accumulated in humans.[3]
Vitamin E exists in 8 different forms: 4 tocopherols and 4 tocotrienols.[2][3] Each form has a chromane ring, and an alkyl side chain, which is hydrophobic. The chromane ring contains a hydroxyl group that can donate a hydrogen atom to free radicals. This reaction helps reduce oxidative damage. In this way, a vitamin E acts as an antioxidant. The hydrophobic side chain helps vitamin E enter biological membranes. In the membrane, the aromatic ring of the chromane (the chromanol ring) lies near the carbonyl groups of the fatty chains of phospholipids. This allows vitamin E to concentrate from the surrounding aqueous solution into biological membranes.[5]
Because vitamin E is lipid-soluble, it is found in many tissues.[2] The body absorbs and distributes vitamin E through several pathways.[3][6] Malaria parasites may use α-tocopherol to protect themselves from the highly oxidative environment in erythrocytes.[7] In cardiovascular disease, α-tocopherol acts as an antioxidant. It can help prevent oxidation of low-density lipoprotein (LDL). Lower levels of oxidation of LDL may reduce atherosclerosis and arterial plaque formation.[8]
Synthesis
[edit]To synthesize the ⍺-diastereomer selectively, tocol acetate is transformed to the naturally occurring, kinetically favored α-tocopherol after being catalyzed by the lipase enzyme. This reaction occurs under biological conditions, commonly in the digestive system.[9]
Stereoisomers
[edit]α-Tocopherol has three stereocenters, so it is a chiral molecule.[10] The eight stereoisomers of α-tocopherol differ in the configuration of these stereocenters.[11]
- RRR-α-tocopherol is the natural one.[12] The older name of RRR-α-tocopherol is d-α-tocopherol, but this d/l naming should no longer be used, because whether l-α-tocopherol should mean SSS enantiomer or the SRR diastereomer is not clear, from historical reasons.[11]
- The SRR may be named 2-epi-α-tocopherol.[11]
- The diastereomeric mixture of RRR-α-tocopherol and SRR-α-tocopherol may be called 2-ambo-α-tocopherol. This mixture can be semisynthetically produced from phytol.[11]
- The mixture of all eight diastereomers is called all-rac-α-tocopherol. This is a commonly chemically synthesized form.[11]
The name dl-α-tocopherol formerly referred to the 2-ambo mixture. When the optical activity of phytol was recognized, the "dl" designation became more associated with the all-rac form. In any case the "dl" designation is vague and should be avoided.[11] The acetate ester of the 2-ambo form, 2-ambo-α-tocopheryl acetate, was the 1941 international standard for vitamin E activity.[11]
Biological equivalents
[edit]The different stersoisomers of α-tocopherol have different degrees of bioactivity when ingested orally. This is due to them having different bioavailabilities, in turn due to their different abilities to bind to the alpha-tocopherol transfer protein (α-TTP) made by the liver.[13] A form that binds α-TTP better is not only more protected from excretion into bile, but also more abundantly transported in blood serum to target tissues. When given as the acetate ester, RRR is the most active stersoisomer (100%), followed by RRS (90%), RSS (73%), SSS (60%), RSR (57%), SRS (37%), SRR (31%), and SSR (21%).[14]
The international unit system defines, for nutritional purposes, one IU of vitamin E as either2⁄3 milligram of RRR-α-tocopherol (d-α-tocopherol) or 0.9 mg of an equal mix of the eight stereoisomers, which is a racemic mixture, all-rac-α-tocopherol. This 0.9 mg is in turn equivalent to 1 mg of all-rac-α-tocopheryl acetate, an ester also known as dl-α-tocopheryl acetate.[15]
Starting with May 2016, the National Institutes of Health has switched to a new system of equivalents called "mg as α-tocopherol". In this new system 1 mg of "Vitamin E" is 1 mg of d-alpha-tocopherol or 2 mg of dl-alpha-tocopherol.[16]
References
[edit]- ↑ Merck Index, 11th Edition, 9931.
- 1 2 3 4 "Vitamin E". Office of Dietary Supplements, US National Institutes of Health. 26 March 2021. Retrieved 20 June 2026.
- 1 2 3 4 "Vitamin E". Micronutrient Information Center, Linus Pauling Institute, Oregon State University. 2026. Retrieved 20 June 2026.
- ↑ Atkinson, Jeffrey; Harroun, Thad; Wassall, Stephen R.; Stillwell, William; Katsaras, John (May 2010). "The location and behavior of α-tocopherol in membranes". Molecular Nutrition & Food Research. 54 (5): 641–651. doi:10.1002/mnfr.200900439. PMID 20166146.
- ↑ Burton, G. W.; Ingold, K. U. (1 June 1986). "Vitamin E: application of the principles of physical organic chemistry to the exploration of its structure and function". Accounts of Chemical Research. 19 (7): 194–201. doi:10.1021/ar00127a001.
- ↑ Rigotti A (2007). "Absorption, transport, and tissue delivery of vitamin E". Molecular Aspects of Medicine. 28 (5–6): 423–36. doi:10.1016/j.mam.2007.01.002. PMID 17320165.
- ↑ Shichiri M, Ishida N, Hagihara Y, Yoshida Y, Kume A, Suzuki H (2019). "Probucol induces the generation of lipid peroxidation products in erythrocytes and plasma of male cynomolgus macaques". Journal of Clinical Biochemistry and Nutrition. 64 (2): 129–142. doi:10.3164/jcbn.18-7. PMC 6436040. PMID 30936625.
- ↑ Singh, U.; Devaraj, S.; Jialal, I. (21 August 2005). "Vitamin E, Oxidative Stress, and Inflammation". Annual Review of Nutrition. 25 (1): 151–174. doi:10.1146/annurev.nutr.24.012003.132446. PMID 16011463.
- ↑ Mizuguchi, Eisaku; Takemoto, Masumi; Achiwa, Kazuo (January 1993). "An enzyme-catalyzed synthesis of natural α-tocopherol". Tetrahedron: Asymmetry. 4 (9): 1961–1964. doi:10.1016/s0957-4166(00)82239-9.
- ↑ Jensen SK, Lauridsen C (2007). "Alpha-tocopherol stereoisomers". Vitamins and Hormones. 76: 281–308. doi:10.1016/S0083-6729(07)76010-7. ISBN 9780123735928. PMID 17628178.
{{cite journal}}: CS1 maint: periodical has ISBN (link) - 1 2 3 4 5 6 7 IUPAC Nomenclature of Tocopherols and Related Compounds, from https://www.degruyter.com/document/doi/10.1351/pac198254081507/pdf
- ↑ Brigelius-Flohé R, Traber MG (July 1999). "Vitamin E: function and metabolism". FASEB Journal. 13 (10): 1145–55. doi:10.1096/fasebj.13.10.1145. PMID 10385606. S2CID 7031925.
- ↑ Jensen, Søren K.; Nørgaard, Jan V.; Lauridsen, Charlotte (March 2006). "Bioavailability of α-tocopherol stereoisomers in rats depends on dietary doses of all-rac - or RRR-α-tocopheryl acetate". British Journal of Nutrition. 95 (3): 477–487. doi:10.1079/bjn20051667. PMID 16512933. Retrieved 31 October 2024.
- ↑ Manolescu B, Atanasiu V, Cercasov C, Stoian I, Oprea E, Buşu C (October–December 2008). "So many options but one choice: the human body prefers alpha-tocopherol. A matter of stereochemistry". Journal of Medicine and Life. 1 (4): 376–82. PMC 5654212. PMID 20108516.
- ↑ "Composition of Foods Raw, Processed, Prepared USDA National Nutrient Database for Standard Reference, Release 20" (PDF). USDA. February 2008. Archived from the original (PDF) on 2012-02-19.
- ↑ "Unit Conversions". National Institutes of Health. Retrieved 2018-11-21.