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Biochemistry: Vitamin E
Vit E
53
Chemistry
Graduate
05/16/2010

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Term
Chromanol (alcohol)ring structure with (-OH) in position 6 + side chain with isoprenoid units (phytyl) is characterized to what vitamin?
Definition
alpha-tocopherol Vit E
Term
Vit E Family include ? And how many?
Definition
4 Tocopherols
alpha
beta
gamma
delta


+

4 Tocotrienols
alpha
beta
gamma
delta

=

VITAMIN E FAMILY
(8 members)
Term
The OH group in Vit E is important for what?
Definition
Antioxidant activity
Term
TE (Tocoherol Equivalents) = __ mg alpha tocopherol
Definition
1TE=1 mg alpha tocopherol
Term
Why only alpha-tocopherol is Vit E for humans?
Definition
Only the stereoisomers (tail is in 2R configuration) of alpha tocopherol are maintained in human body.
Term
Natural Vit E
Definition
RRR-α-tocopherol (d-α-tocopherol)
IN FOODs
- formed by methylating gamma tocopherol extracted from vegetable oil.
Term
Synthetic Vit E
What form is it usually in?
Definition
all-rac-α-tocopherol
8 stereoisomers: RRR, RRS, RSR, RSS, SRR, SSR, SRS, SSS
1/2 as good as natural
- produced by coupling trimethylhydroquinone with isophytol
- 8 stereoisomers in equal emount
- Found in fortified food
- usually in ester form (acetate)
Term
Why is synthetic form of Vit E is only 1/2 as good?
Definition
Natural Vit E: one stereoisomeric form
Synthetic: 8 possible stereoisomers, but serum and tissues only maintain 4 four, of these stereoisomers. So synthetic Vit E (DL or dl) is only 50% active as same amount of natural Vit E (D or d) *by wt in mg
- ppl need 50% more IU of synthetic α-tocopherol
Term
RDA of Vit E in Adults
Definition
15 mg/ day (30 if its all rac α tocopherol)
Term
Vit E absorption and delivery to tissues?
Definition
1. Vit E absorption required BILE ACID, FATTY ACIDs, and MONOglycerides for micelle formation
2. Once Vit E is taken in by enterocytes, all formas of dietary Vit E are incorporated into Chylomicrons
3. CM are secreted into the circulation
4. In circulation--> lypolysis by LPL bound to the endothelial lining of capilarry walls takes place
5. Resulted CM taken up by liver
6. During lipolysis: various forms of Vit E can be transferred to tissues, or to HDL
7. Vit E can exchange between HDL or other circulation lipoproteins, which can also deliver vit E to peripheral tissues
Term
Circulating HDL and other lipoproteins can also deliver Vit E to tissues. T of F
Definition
TRUE
Term
Draw absorption and delivery of Vit E. Page 6
Definition
Term
How is α-tocopherol delivered to tissues?
Definition
1. CM remnants with Vit E (various forms) are taken up by LIVER
2. α-TTP prefers to take α-tocopherol into naschent VLDL
3. When VLDL secreted in PLASMA, lypolysis of VLDL by LPL and hepatic TG lipase result in preferred enrichment of circulating lipoproteins with α-tocopherol and its delivery to tissues.
Term
Draw the delivery of VIt E diagram. Page 7
Definition
Term
How much Vit E is absorbed? (%)
Definition
About 20-40 % of dietary vit E
Term
How is α-tocopherol mainly transported?
Definition
Via VLDL fraction in plasma
Term
Where is Vit E stored?
Definition
Vit E stored in
- adipose (FAT)
- Liver
- Muscle
Term
Vit E is found in tissues mainly in what form?
Definition
As Free tocopherols, in cell membranes
Term
How is Vit E excreted and in what form?
Definition
In
bile
urine as derivatives of tocopherol quinone.
Term
Functions of Vit E?
Definition
Antioxidant Function:
- Major membrane bound, lipid soluble antioxidant
- it is a hydroxy/peroxyl radical trapping and chain breaking antioxidant
- Oxidized Vit E is regenerated by the glutathone system or vit C

Structure specific functions:
- regulation of vascular smooth muscle cell proliferaton
- Prtein Kinase C activity
- Arachidonic acid metabolism (inhibition of phospholipase A2)
- Degragation of HMG-CoA reductase
- Gene expression?
Term
What is the major membrane bound, lipid souluble antioxidant?
Definition
Vit E
Term
Which antioxidant is hydroxyl/peroxyl radical trapping and chain breaking?
Definition
Vit E
Term
Degragation of HMG- CoA reductase? Which Vitamin
Definition
Vit E
Term
Arachidonic acid metabolism *inhibition of phospholipase A2, which vitamin?
Definition
Vit E
Term
Regulation of smooth muscle cell proliferation, which vitamin?
Definition
Vit E
Term
Importance in Protein Kinase C activity, which vitamin?
Definition
Vit E
Term
Lipid Peroxidation VIT E?
What is the end product?
Definition
Initiation: Production of R*
- due to attack of things that capable of taking H from UNsaturated FA to from Carbon centered radical

Propagation:
Carbon-centered radical reacts fast with O2
R+O2 --> R-OO
- a fatty acid peroxyl radical is formed. This can attack adjacent FA side chain and promote peroxidation
R-OO + RH--> R-OO-H +R
This chain Rx continues, lipid hydroperodides (R-OO-H) destabilze membrane--> leaky
Termination:

Requires chain breaking antioxidant
R-OO + αTH--> R-OO-H + α T

ENd product: ethane, pentane, MDA
Term
Vit E needs what to regenerate?
It produces VIt E and _____?
Definition
Vit C, glutothione
Dehydro ascorbate
Term
Why can't Saturated FA be oxidized?
Definition
Becaue oxidation happens at the double bond
Term
What does AVED stand for?
Definition
Ataxia w/ Vit E deficiency
Term
Deficiency of Vit E: Defects in lipoprotein synthesis
Definition
Apoliprot B: rapid turnonver of B lipoprotein in plasma
(homozygous hypobetalipoprotenemia)

- microsolmal TG transfer protein (abetalipoproteinemia): No B lipoproteins in plasma
- both develop a progressive peripheral neuropathy
- must supplement with VitE
Term
Hypobetaliproteinemia
Definition
Rapid turnover of B lipoprotein in plasma
Term
Abetalipoproteinemia
Definition
no B lipoprotein in plasma--> develop progressive peripheral neuropathy
Term
Fat malabsorption syndrome and Vit E
Definition
Who:
Children w/ cholestatic liver disease
Children w/cystic fibrosis
Bowel resection, Crohn's disease, celiac disease
TPN
Treat:
RRR-α-tocopherol (not the ester)
Water soluble form: tocopherol polyethylene glycol 1000 succinate (TPGS)
- Intramuscular injection: Viprimol
Term
What is a water soluble name for Vit E?
Definition
TPGS
Tocopherol polyethylene glycol 1000 succinate
Term
Disorders in which Vit E is beneficial (lucky 7)?
Definition
Premature infants-retinopathy of prematurity
- protetion from retrolental fibroplasia
- possible protection from intraventricular hemorrhage

Anemia of prematurity:
- physiological jaundice anemia of newborns
CV disorders:
decreased risk of CHD
decreasedin vitro LDL oxi
decreased in vitro platelet aggrigation

Ischemia-reperfusion injury (blood supply cut off, then comes back)
Immune response
Cataract
Tardive dyskenesia (involuntary, repetitive body movements)
Term
What is EAR, DRA and UL of Vit E?
Definition
EAR: 12 mg/d
RDA: 15 mg/d
UL: 1000 mg/day
Term
Vit E and CVD?
Definition
α tocopherol inhibits oxidation of LDL in vitro
Term
What causes free radical?
Definition
inflammation, phagocytosis, detox enzymes, mitochondria, smoking, uv, smog, radiation, chemicals
Term
Oxygen paradox
Definition
O2 is involved in making reactive oxy species (ROS) and reactive N species (RNS)
- contain one or more unpaired e
- highly reactive
Term
Physiological Antioxidant System: Endogenous
Definition
Active system
Enzymes: catalase,superoxide dismutase, glutathione peroxide, paraoxonase

Passive system:
Uric acid, createnine, bilirubin, melatonin, glutathione NAD(p)H, lipoic acid, CoQ, albumin, transferin, ceruloplasmin, haptoglobin
Term
Physiological Antioxidant System: Exogenous
Definition
Nutrients: Vit E, Carotenoids, Vit C
- Dietary biocactive components: polyphenols
Term
What is body's antioxidant defense in Plasma?
Definition
Vit C (ascorbic acid)
B- carotene and other carotenoids
Plasma proteins
Uric Acid
Bioactive plant compoinds
Enzyme system:
ceruloplasmin
Superoxide dismutase
Glutathione peroxidase
Term
What is body's antioxidant defense in Membrane?
Definition
α-tocopherol or Vit E
beta carotene
Term
What is body's antioxidant defense Intracellularly?
Definition
GLUTATHIONE
enzyme system: superoxide dismutase
catalase
glutathione peroxidase
Term
How are Free radicals useful?
Definition
Respiratory chain
NO (from arginine)--> vasodilator
Phagocytic cells: produce superoxide which helps inactivate viruses and bacteria
Term
Biomarker for lipid oxidation?
Definition
TBARS
breath hydrocarbons
LDL resistance to oxidation
F2 isoprostanes
ORAC, FRAP
Term
Biomarker for DNA oxidation?
Definition
8 OHdG
antibodies to oxidize DNA
Comet assay (dna strand breaks, dna oxi)
Term
Biomarker for protein oxidation?
Definition
Protein carbonyls
Term
Formation and Removal of OH, Singlet oxygen O2 and Superoxide?
Definition
OH:
Form: ionizing rediation
Remove: ascorbic acid, carotenoids

Singlet Oxy O2:
Form: light energy
Remove: Vit E, carotenoids

Superoxide O2:
Form: phagocytosis, metabolic reactions
Remove: Superoxide dismutase SOD
Term
Hydrogen Peroxide
Definition
Form: SOD enzyme, oxidase enzyme
Remove:
1. Catalase (Fe) in peroxisomes of cells
2. Glutathione peroxidase system:
enzyme glutathione peroxidase destroys OH
1. GSH (reduced)--> GSSG (oxidized)

2. GSSG (oxidized) is re generted by glutathione reductase

Glutathione peroxidase also destroys lipid hydroperoxides
Term
Glutathione peroxidase system?
Definition
Enzyme: Glutathione peroxidase destroys hydrogen peroxide
1. GSH--> GSSG (reduced-->oxi)
2. GSSG *oxidized is re-generated by glutathione reductase
GSSG+NADPH--> GSH + NADP

Glutathione peroxidase also destroys lipid hydroperoxides
Term
Glutathione
Definition
Reduced: GSH (tripeptide, in most cells)
Can scavange free radicals directly and its part of the glutathione peroxidase system

Glutamate+cystein+glycine
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