Vitamin E Flashcards
What is the general term for the vitamin E isoforms?
Tocochromanols
* General term for structurally similar compounds which exhibit the activity of RRR-α-tocopherol
* Covers 8 different compounds Just by small changes to structure
Classification of the vitamin E isoforms
What is the active isoform of vitamin E?
𝝰-tocopherol
General structure of Tocopherols and tocotrienols
The structure has 2 parts
* head group with methyl substitutions at R1, R2 and R3 which can change the structure
* phytate chain (FA chain) which has double bonds for the tocotrienols but not for tocopherols
What impacts natural vitamin E activity?
- position of methyl group
- Addition of double bonds
Structure and Activity of Naturally- Occurring forms of Vitamin E
- additions of double bonds reduces vitamin E activity
Synthetic Forms of α-Tocopherol
- Esterified at the phenolic hydroxyl group
- 3 chiral centres → mixed isomers
why is synthetic 𝝰-tocopherol esterified?
Increases stability of a supplement
* Ester usually gets cleaved off during digestion to liberate the active form of a-tocopherol
Difference between natural and synthetic 𝝰-tocopherol
the natural has biologically set chiral centres but the synthetic form may be mixed and this can reduce activity
What is the biological activity of Vit E affected by for natural and synthetic?
- The presence of double bonds in the phytyl tail
- The location of methyl groups on the phenolic ring
- Configuration of the 3 chiral centres (synthetic only)
- Esterification of the phenolic ring (although hydrolyzed in digestive tract)
Tocochromanol Absorption
VitE isoforms are non-polar molecules that are incorporated into micelles in the gut and enter enterocyte via passive diffusion where they are incorporated into the middle of Chylomicrons and secreted into lymph.
* ~50% of dietary tocochromanols are absorbed
* remaining excreted in feces
* Esterases cleave synthetic forms to free tocopherol
General lipid absorption
- fat globule is emulsified by bile salts and forms micelles (containing vitE)
- passive diffusion of micelle into enterocyte
- packaged into TG rich CM
- secreted into lymph
Tocochromanol Transport
- VitE is transported in CM and most is delivered to liver in CMr.
- α-tocopherol transfer protein (α-TTP) preferentially binds 𝝰-toco and can transfer it between membranes
- Repackaged into VLDL for delivery to other tissues
- Some may also be transferred to HDL via ABCA1 (ATP-binding cassette protein A1)
Intracellular metabolism of tocochromanol in the hepatocyte (what happens when vitE reaches the liver?)
Essentially the metabolic processes in the hepatocyte concentrate the 𝝰-tocopherol form.
* CMr come back to liver
* Uptake is receptor mediated endocytosis
* During intake, aTTP preferentially recognizes 𝝰-toco and transfers it into different membranes (bile, VLDL, HDL)
* Other isoforms are broken down by ER and mito to soluble forms and are excreted
How are Tocochromanols excreted?
Efficiently metabolized for excretion (Does not exceed >2-3 x [plasma]) the VitE breakdown converts it from lipid soluble to aqueous soluble which can then be excreted via tocopherol-ω- oxidation
Tocochromanol Breakdown
Breakdown chain and make it smaller and excretion can occur through bile or through urine
* Initiated by CYP-4F2
* truncation of the phytyl side chain to 2’-carboxyethylhydroxychromanol metabolites (CEHC’s)
* Conjugated to glucuronic acid/sulfates for urinary (or biliary) excretion
How are tissues enriched with 𝝰-tocopherol?
α-TTP -preferentially binds α-tocopherol repackaging it while CYP-4F2 has lowest affinity for 𝝰-toco so other isoforms are broken down/ excreted.
Vitamin E storage
Intracellularly, vitamin E is stored in membranes but nosingle storage organ for vitamin E
* 90% of vitamin E is stored in white adipose tissue – very immobile pool and cannot adequately supply vitamin E to circulation in times of need
* Vitamin E in liver and RBC is readily available to be redistributed to places where needed
Where do free radicals target in disease?
- PUFAs
- DNA + RNA
- Proteins
How does the lipid oxidation chain reaction occur?
- hydroxyl radical occurs in aqueous solution which can attack lipids, proteins and DNA causing a lot of damage.
- Initiation (oxidation of membranes): hydroxyl radical will react to the double bonds in PUFA so get an unbalance of the electrons and it becomes reactive lipid radical.
- The lipid radical can then react with oxygen making the lipid peroxide radical which is very reactive species
- Propagation (continueing chain reaction): The lipid peroxide radical can then attack another lipid resulting in lipid hydro peroxide + another radical produced which continues down the membrane.
How does vit E work to protect against the propagation of lipid oxidation?
Vit E quenches the chain reaction by scavenging free radicals
* can react with the lipid radical and become one itself. We still get the lipid hydroperoxide but we stop the lipid radical from forming and the vit E radical does not react with other things.
How is the LOOH removed?
Can be reduced to a lipid alcohol via the glutathione peroxidase system which is less reactive
How is the tocopheroxyl radical recovered?
reduced back to 𝝰-toco by vitamin C
* Cox then reduced by 2 GSH
* GSSG then reduced by glutathione reductase
Rich sources of tocopherols
- animal fats
- Oil seeds and vegetable oils (especially safflower)
- Leafy green vegetables (Broccoli, spinach)
- Fortified breakfast cereals
Vit E role in CVD Prevention
reduced CVD risk at higher intake of VitE
* Fewer atherosclerotic plaques
* Lower risk of CVD-induced mortality
LDL goes into interstitial space and gets oxidized forming foam cells and vessel eventually gets blocked (oxidative process); higher vitamin E may lower risk of athersclerosis
Potential mechanisms of vit E preventing atherosclerosis
- Reduces free radical-induced oxidation
- Protects against LDL oxidation
- Decreases blood clotting
Vit E: Role in Cancer
may be benefit in prostate cancer
Vit E on all cause mortality
No effect on all-cause Mortality
Meta of all cause mortality intervention
