The association of the tocopherols with lipid peroxidation in biological systems began in the early days of investigations on the chemical nature of these substances (25). Since then a great deal of work has attempted to relate the symptoms of vitamin E deficiency with peroxidative degradation of lipids, primarily those associated with membranous organelles. The signs of vitamin E deficiency in various species of animals are diverse, involving different tissues with different manifestations and different degrees of severity. Thus, it seems clear that the biological function of this vitamin is not specific in the sense of its being a cofactor for an enzymic reaction (as is the case for the B-complex vitamins). Given the appropriate species and certain dietary and environmental conditions, essentially any tissue can be made to develop characteristic signs as a result of a deficiency of this vitamin. In some human disease states, supple­ mentation of vitamin E at levels far exceeding those normally required amelio­ rates or improves the condition. Because of this multiplicity of effects, a common denominator that might explain the effects of a deficiency or excess of this vitamin is not obvious. A common denominator to consider, however, is

VITAMIN E: Interactions With Free Radicals and Ascorbate

Vitamin E (α-tocopherol) is essential for the prevention of photo-oxidative deterioration of biomembranes. The occurrence, relative biological activity and distribution of tocopherols in photosynthetic membranes is considered together with the possible biochemical and biophysical mechanisms by which tocopherols confer protection upon illuminated membranes. The common protective effects of Vitamin E in photo-synthetic membranes and in medically important light-induced diseases and conditions of the skin and eye in animal cell membranes are discussed. The importance of the Vitamin E-Vitamin C thylakoid antioxidant system is also examined, in terms of susceptibility to photo-oxidative damage under stress conditions including chilling, ageing and senescence, drought, atmospheric pollutants, herbicides and photosensitizing fungal toxins.

The antioxidant effects of thylakoid Vitamin E (α-tocopherol)

If the function of vitamin E is that of an antioxidant and the various forms of vitamin E have similar antioxidant activities, then why does RRR-alpha-tocopherol have the highest biologic activity? This chapter describes how interactions by investigators from various scientific disciplines using stable isotopes, molecular biology tools, and sophisticated genetic studies of humans with vitamin E deficiency have led to an understanding of this problem. This chapter provides an overview of (a) studies using deuterated tocopherols that demonstrated that the plasma preference for alpha-tocopherol is dependent on metabolic processes in the liver; (b) the isolation, molecular biology, and function of the alpha-tocopherol transfer protein; and (c) studies that demonstrated that patients who were vitamin E deficient as a result of no known cause had defective alpha-tocopherol transfer protein genes. Finally, we focus on the future--what remains to be learned about the regulation of vitamin E in tissues.

Molecular mechanisms of vitamin e transport

Vitamin E is the term used for eight naturally occurring fat-soluble nutrients called tocopherols. alpha-Tocopherol is essential, has the highest biological activity and predominates in many species. In humans vitamin E is the most important lipid soluble antioxidant and deficiency may cause neurological dysfunction, myopathies and diminished erythrocyte life span. alpha-Tocopherol is absorbed via the lymphatic pathway and transported in association with chylomicrons. In plasma, alpha-tocopherol is found in all lipoprotein fractions but mostly is associated with apo B-containing lipoproteins. alpha-Tocopherol is associated with very-low-density lipoprotein when it is secreted from the liver. In the rat, about 90% of total body mass of alpha-tocopherol is recovered in the liver, skeletal muscle and adipose tissue. Most alpha-tocopherol is located in the mitochondrial fractions and in the endoplasmic reticulum, whereas little is found in cytosol and peroxisomes. New clinical evidence from heavy drinkers and from experimental work in rats suggests that alcohol may increase oxidation of alpha-tocopherol. Increased demand for vitamin E has also been observed in premature infants and patients with malabsorption, but there is little evidence that the healthy population requires supplementation of vitamin E to a well-balanced diet.

Absorption, transport and distribution of vitamin E.

The main research activities of the last decades on tocopherols were mainly focused on alpha-tocopherol, in particular when considering the biological activities. However, recent studies have increased the knowledge on gamma-tocopherol, which is the major form of vitamin E in the diet in the USA, but not in Europe. gamma-Tocopherol provides different antioxidant activities in food and in-vitro studies and showed higher activity in trapping lipophilic electrophiles and reactive nitrogen and oxygen species. The lower plasma levels of gamma- compared to alpha-tocopherol might be discussed in the light of different bioavailability, but also in a potential transformation from gamma- into alpha-tocopherol. From the metabolism end product, only that of gamma-tocopherol (2,7,8-trimethyl-2-(beta-carboxyethyl)-6-hydroxychroman), but not that of alpha-tocopherol, was identified to provide natriuretic activity. Studies also indicate that only the gamma-tocopherol plasma level served as biomarker for cancer and cardiovascular risk. Therefore, this paper provides a comprehensive review on gamma-tocopherol with emphasis on its chemistry, biosynthesis, occurrence in food, different intake linking to different plasma levels in USA and Europe, absorption and metabolism, biological activities, and possible role in human health.

Gamma-tocopherol--an underestimated vitamin?

http://www.jbc.org/content/113/1/319.full.pdf

THE ISOLATION FROM WHEAT GERM OIL OF AN ALCOHOL, α-TOCOPHEROL, HAVING THE PROPERTIES OF VITAMIN E

We have prepared from the non-saponifiable matter of wheat germ oil thress aflophanates:

1. M.p. 250°. This is a possibly the allophante of β-amyrin. The alcohol regenrated from the allopohante has no vitamin E potency.

2. M.p. 138°, readily crystallizing in long needles. The analysis agree with values required by monollophantes of an alcohol, C39H50O2. The alcohol from this allophante apparenelly has some vitamin E potency, but less than that from the third allophanate.

3. M.p. 158-160°. From this allophanate, the alcohol—for which we propose the name α-tocopherol—when given in a single dose of 3 mg. always enables vitamin E-deficient rats to bear young. α-Tocopherol shows a characteristic absoption band at 2980 A., E1 per cent1 cm. = 90 ca. Treatment with methyl alcoholic silver nitrate converts it to a substance which has absorption bands at 2710 and 2620 A respectively, E1 per centcm. = 480 ca., and possesses and some vitamin E activity.

α-Tocopherol yields a crystaline p-nitrophenylurethane melting at 120-131°. Analyses of both the urethane and the allophanate indicate a provisional formula for α-tocopherol of C29H50O2

Gladys A. Emerson

Papers

THE ISOLATION FROM WHEAT GERM OIL OF AN ALCOHOL, α-TOCOPHEROL, HAVING THE PROPERTIES OF VITAMIN E

The Isolation from Wheat Germ Oil of an Alcohol, α-Tocopherol, Having the Properties of Vitamin E

The chemistry of vitamin e tocopherols from various sources

The antiriboflavin effect of galactoflavin

Role of vitamin E in the prevention of muscular dystrophy in guinea pigs reared on synthetic rations