Vitamin E

What are the dietary sources of vitamin E?

Vitamin E is synthesized in plants. It is fat soluble so it is most commonly found in various plant oils (e.g. sunflower oil, safflower oil, peanut butter, etc)

Describe transport of vitamin E

Vitamin E that has been packaged into chylomicron remnants is released into circulation and it taken up by the liver. The liver regulates vitamin E release into circulation, metabolism, and excretion.

Describe liver metabolism of vitamin E

α-tocopherol transfer protein (α-TTP) in the liver will facilitate the incorporation of vitamin E into VLDLs which are then exported into the plasma (α-TTP has the highest affinity for the α-tocopherol form of vitamin E). VLDLs in circulation undergo lipolysis and either are broken into LDLs and HDLs to facilitate tissue uptake of α-tocopherol or they are recycled back to the liver.

Describe the process of lipid peroxidation and how vitamin E is able to act as an antioxidant.

(1) An unsaturated lipid becomes a lipid radical when a free radical such as a hydroxyl radical (OH-) attacks a double bound in a PUFA, which removes an H atom (2) The lipid radical readily reacts with molecular oxygen (O2) to form a lipid peroxyl radical (3) The lipid peroxyl radical can readily extract a H atom from an adjacent PUFA and form a new lipid radical This chain reaction is interrupted by vitamin E. The structure of vitamin E allows for H to be donated to free radicals. Vitamin E terminates the chain-propagation; it is oxidized during termination and must be regenerated.

Identify causes of vitamin E deficiency (i.e. identify at-risk populations)

- Fat malabsorption disorders (e.g. cystic fibrosis and chronic cholestasis): vitamin E is a fat soluble vitamin and poor fat absorption will inhibit vitamin E absorption - Pancreatic insufficiency: pancreatic esterases are responsible for hydrolyzing vitamin E - Persistent steatorrhea - Abetalipoproteinemia (inability to form chylomicrons): vitamin E can't be incorporated into chylomicrons and transported to the liver for metabolism - Genetic defect in α-TTP: no preferential selection for α-tocopherol - Premature infants

Describe the 2 mechanisms that promote the retention of α-tocopherol in the body

1) α-tocopherol is a poor substrate for catabolic pathway which plays an important role in the selective retention of α-tocopherol (i.e. less α-tocopherol is excreted compared to other forms) 2) α-TTP prefers α-tocopherol; this means that α-tocopherol is more likely to be incorporated into VLDLs and ultimately used by tissues and therefore, less is available to be excreted

Describe the structures of vitamin E: natural vs. synthetic form of vitamin E

In nature, tocopherols only exhibit the RRR stereoisomer of alpha-tocopherol. In contrast, the synthetic form of vitamin E contains a racemic mixture of all 8 stereoisomers of alpha-tocopherol (i.e. all rac alpha-tocopherol). Vitamin E used in supplements is often chemically stabilized (esterified) to prevent oxidation. Modifying alpha-tocopherol extends shelf life and used in supplements and fortification.

Explain the adverse effects of vitamin E toxicity

The adverse effects of vitamin E toxicity include hemorrhagic effects. Vitamin E causes abnormal blood coagulation in animal studies, resulting in hemorrhages of the GI and urinary tracts. Vitamin K supplementation can reverse this but individuals on anticoagulant or low vitamin K diets may be at risk for abnormal coagulation if given high doses of vitamin E.

Describe the function of vitamin E

The principal function of vitamin E is to act as an antioxidant dedicated to lipids (primarily an antioxidant for phospholipid bilayers). Vitamin E functions to protect membrane integrity by preventing the oxidation of unsaturated fatty acids within the phospholipid bilayers. The phospholipids of the mitochondria and the endoplasmic reticulum are at the greatest risk. Tissues at the highest risk to oxidation are the lungs, brain, and RBCs because these are exposed to oxygen all of the time.

Describe excretion of vitamin E

Tocopherols/trienols undergo extensive catabolism that leads to either bile or urinary excretion. They are metabolized to CEHCs which are conjugated with glucuronic acid or sulfates, and then excreted in urine or bile. NOTE: α-tocopherol is a poor substrate for catabolic pathway which plays an important role in the selective retention of α-tocopherol

Describe the structures of vitamin E: 8 vitamers

Vitamin E consists of: - a chromanol structure (2-ring structure) - a saturated (tocopherol) or unsaturated (tocotrienol) side chain. There are variations in the number and position of methyl groups to produce alpha, beta, gamma, and delta tocopherols and tocotrienols (8 distinct forms)

Describe what can happen to vitamin E after it has been absorbed in the intestines.

Vitamin E in the intestines is packaged into chylomicrons which undergo lipolysis by LPL (lipoprotein lipase). After this process, vitamin E can be packaged into chylomicron remnants for liver uptake or it can be transferred to tissues or to HDLs for tissue uptake. NOTE: All forms of vitamin E are absorbed and incorporated into chylomicrons - no one form appears to be preferentially absorbed from the intestine (how vitamin E is packaged into a chylomicron is not known).