Vitamin E Flashcards
Vitamin E encompasses how many compounds?
8 total
-4 tocopherols
-4 tocotrienols
Which form of vitamin E has the highest antioxidant activity?
Alpha-tocopherol
Then:
-Beta
-Gamma
-Delta
Which class of vitamin E compounds is more abundant and more nutritionally relevant? Why?
Tocopherols - saturated tail is better for antioxidant capacity
The tocotrienols - have double bonds, which does not make them very good for antioxidant activity
What are the structural differences between the two main groups of vitamin E derivatives?
The position of the methyl group
Which group of vitamin E derivatives are less widely distributed in nature (in our foods) and thus considered less nutritionally important?
Tocotrienols
Which vitamin E derivative has the highest antioxidant activity?
Alpha-tocopherol
1 mg of the naturally occurring vitamin E in alpha-tocopherol is equivalent to XXX of the supplemental form.
2 mg; so the supplemental form is only half as active as the nature form
How is vitamin E absorbed into the enterocytes?
Via passive diffusion
(TRUE/FALSE)
Vitamin E supplements taken on an empty stomach are absorbed well.
FALSE; supplements are half as active, and without fat they are not very well absorbed
What form are the fat-soluble vitamins generally in, when coming from the diet?
Ester form (remember: meaning they are attached to FAs)
What enzyme from the SI hydrolyze the vitamin from the FA?
Esterase
How are the micelles formed?
Free vitamin E (and other fat-soluble vitamins), combined with bile acids secreted by the liver.
Once the micelles are formed, what happens next as part of digestion?
The micelles enter the enterocyte, and vitamin E, D, K go directly into the Chylomicron
Once the chylomicron exits the enterocyte, where does it go?
Into the lymph system, then into cirulation
What happens once the CM enters circulation?
The CM will deliver the fat-soluble vitamins, TGs and cholesterol throughout the body
What part of the CM will be distributed through HDL?
Vitamin E
So in circulation, the CM will give some of its contents (including vitamin E) to HDL
What happens to the chylomicron remnant?
The CM remnant will be taken up by the liver, and it will be repackaged into VLDL particles.
OR
Vitamin E (within the liver) can be:
1. Excreted as part of bile, which will go into the intestines (and reabsorption via enterohepatic circulation) or excreted via feces
2. Metabolized and excreted in urine
3. Packaged up and put into VLDL (THIS IS THE MAJORITY!!!)
What happens once the VLDL is formed?
It will exit the liver, and enter the circulation.
VLDL will be carrying more FAs and cholesterol (that has been made in the liver)
What vitamin E derivative will be incorporated into the VLDL?
ONLY alpha-tocopherol
Because the other forms are poorly recognized by the liver and have not been well-absorbed either.
What does alpha-tocopherol (via VLDL) do?
- Interact w/ HDL and some may be transferred to HDL
- Remain on LDL
- Interact with peripheral tissues and be taken up (really talking about ADIPOSE TISSUE HERE).
But, eventually, the VLDL will be converted to LDL. The tocopherol will be distributed to tissues, mainly via the LDL particle.
Also, this is where vitamin E plays an important antioxidant role via protection of the LDL from oxidation.
How does vitamin E play an important antioxidant role?
Tocopherol is distributed to tissues, primarily by LDL, and may play a role in protecting LDL from oxidation. This is important, as oxidized LDL is a risk factor for CVD.
Where is the primary storage area of vitamin E?
Adipose tissue
Smaller amounts in: liver, lung, heart, adrenal gland
Where can vitamin E be excreted?
Fecal route (because of its low intestinal absorption)
& SKIN
(TRUE/FALSE)
Most ingested vitamin E is eliminated by the fecal route because of its low intestinal absorption.
TRUE
There is low bioavailability with low-fat diets
What is the sole function of vitamin E?
To act as an antioxidant; specifically, due to its structure.
The phenol ring is able to donate hydrogen atoms to free radicals in aqueous environments, such as blood.
(TRUE/FALSE)
Vitamin E deficiency symptoms are dependent not only on vitamin E intakes/levels, but also on the degree of oxidative stress and who are taking in high amounts PUFA within the diet.
TRUE
(TRUE/FALSE)
PUFA are unsaturated fats, therefore, are more likely to be subjected to higher levels of oxidation because of the double bonds.
TRUE
So vitamin E helps prevent PUFAs from becoming oxidized
(TRUE/FALSE)
PUFAs are located within the cell membrane, phospholipid bi-layer.
TRUE
They increase fluidity of the cell membrane, which is good for CVD; however, they are more prone to radicals, becoming lipid radicals
*OH
Hydroxyl radical
O2*
Superoxide radical
H202
Hydrogen Peroxide
Not considered a radical but it is pro-antioxidant, and can initiate lipid peroxidation in the exposed cell membranes
What is the way that lipid radicals occur?
The reaction between the lipid compound (ie: PUFA part of the cell membrane), and a free hydroxyl (*OH) radical.
Specifically, the free hydroxyl radical will take an electron from the PUFA
LH + OH —-> L + H2O (creating water and a lipid radical, so now we have an unstable PUFA)
Explain LH + O2 —-> L* + HO2
A lipid, such as a PUFA, will react with molecular oxygen, forming a lipid radical but also, producing a hydroperoxyl radical.
So, we have two radicals forming from two fairly stable molecules. 02 is slightly more pro-antioxidant
L*
The formation of lipid radicals that are of concern, in terms of, pro-antioxidant and the activity of vitamin E.
LOO*
Lipid peroxyl radical; formed by L* (lipid radicals) reacting spontaneously with O2
HIGHLY REACTIVE, it is going to want to find a pair for its lone electron, and it can do that by reacting with another PUFA
LOO* + LH ——> L* + LOOH
The LOO* (lipid peroxyl radical) steals an electron from a PUFA that is in the cell membrane. As a result, one lipid the LOOH is stabilized (aka lipid hydrogen peroxide).
And, we still have a lipid radical (L*) to deal with. This is referred to as a SELF-PROPAGATING REACTION
LOOH
Lipid hydroperoxide; is stable, but the function of this lipid is different because it has been modified (structurally)
Self-Propagating Reaction
Where the lipid radicals want to stabilize themselves, and there is not antioxidants in place that can neutralize this radical and stop this self-propagating sequence
aka endogenous antioxidant systems
Endogenous antioxidant systems
Glutathione
Superoxide dismutase
Exogenous antioxidant sources
Vitamin C
Vitamin E
HOO*
Hydroperoxyl radicals
What type of radicals can vitamin E interact with? (Hint: 2)
- HOO* (hydroperoxyl radical) - before they interact with PUFA in cell membranes
- Lipid radicals
How does vitamin E function as an antioxidant?
Vitamin E acts as a “free-radical scavenger” by….providing a hydrogen to HOO* (hydroperoxyl radicals) and to lipid radicals; however, this does result in vitamin E becoming oxidized
Vitamin E radicals
Occurs when vitamin E donates it’s hydrogen (functioning as an antioxidant)
This is not a reactive type of radical, it does NOT interact with lipids, causing oxidative damage, or in the self-propagating cycle.
These are neutralized by vitamin C (using NADPH and glutathione)
Where does vitamin E have the most antioxidant activity?
In the cell membrane
because it is preventing the oxidation of those PUFAs that are part of the phospholipid bilayer. This is where the free radicals are; specifically, in the tissues with the highest risk for oxidation: LUNG, BRAIN, and RBCS.
Explain the chain-breaking antioxidant activity of vitamin E.
Vitamin E is going to react with the peroxide radical and neutralize it.
As a result, we end up with:
-A lipid hydroperoxide (which has been modified, so it will function differently, but it is stable).
-Vitamin E radical
How does the vitamin E radical get regenerated back to vitamin E?
Vitamin C is going to reduce this vitamin E, donating one of it’s electrons, so vitamin E can now function as an antioxidant again
(TRUE/FALSE)
Vitamin E protects LDL from oxidation.
TRUE, by preventing the propagation initiated by free radical attack.
Oxidized LDL
Once LDL becomes oxidized, this can easily be one of the first steps that is leading to atherosclerosis. Resulting in a pro-inflammatory state within the endothelial cells of the arteries and the circulatory system.
It is believe that vitamin E circulating as part of that LDL particle, can protect it from being oxidized
(TRUE/FALSE)
Vitamin E deficiency is extremely common.
FALSE
Vitamin E is very rare in the healthy population.
What are the at-risk populations for frank vitamin E deficiency?
-Fat malabsorption disorders (such as Crohn’s Disease, IBS)
-Pancreatic insufficiency
-Genetic defect in alpha-TTP (tocopherol transfer protein)
-Premature infants
Alpha-TTP
A hepatic protein that will help to transfer vitamin E from the chylomicron remnant over to the VLDL. And that is where the vitamin E will be on board the lipoprotein that is going to be secreted from the liver.
Defects in this protein: can result in the accumulation of vitamin E in the liver, where it will accumulate or be excreted in bile, or via the feces.
Encephalomalacia
aka “Crazy Chick Disease;” Common symptoms of vitamin E deficiency seen in adults
-Poor motor coordination, resulting in odd head movements
-Ataxia
-Head retraction
-Hemorrhages of capillaries in the cerebrum due to lack of antioxidant activity, thought to be caused by toxic products of linoleic acid oxidation
Red Cell Hemolysis
Associated with vitamin E deficiency, where hydrogen peroxide will cause the rapid hemolysis of RBCs from vitamin E-deficient animals
This can happen within other cells as well (hemolysis)
(TRUE/FALSE)
Vitamin E toxicity is common.
FALSE; it is one of the least toxic vitamins, as it is rare to absorb a toxic amount of vitamin E
(TRUE/FALSE)
High doses of vitamin E can interfere with the action of vitamin K.
TRUE
People who have a marginal vitamin K status or who are taking anticoagulants, like Warfarin can have bleeding problems if very high doses of vitamin E are consumed
How is vitamin E measured?
Serum vitamin E is sufficient for assessing dietary intake and absorption
Less than 5 micrograms/mL indicates a deficiency
RBCs hemolysis test can also be used (usually in lab setting, sometimes in clinical setting)
