Vitamin E

1. VITAMIN E: BY: VERMA NISHU(MBBS)

2. introduction • Vitamin E is a group of 8 fat soluble compounds that include four tocopherols and four tocotrienols. • It is chemically k/a tocopherol. (Greek: tocos=childbirth , piro=to bear and ol=alcohol) • Vitamin E is the name given to group of tocopherols and tocotrienols • Vitamin E is a the principle membrane-associated antioxidant molecule in mammals. • It plays a major role in preventing oxidative damage to membrane lipids by scavenging free radicals.

3. Chemistry of Vitamin E name given to a group of Tocopherols and Tocotrienols. • Vitamin E is a Tocopherols derivatives of Tocol (Chromane ring) with an isoprenoid side chain (3 units ) • 8 derivatives of Tocopherols identified as alpha,beta,gamma,delta Tocopherol etc. • Tocol (Chromane ring) present in all 8 derivatives naturally occurring sources of vitamin E ) along with an isoprenoid chain (3 units ) • Tocotrienols have 1-50% activity of activity of Tocopherols • OH group of Tocol is responsible for antioxidant property of Vitamin E • Vitamin E acts as scavenger and gets oxidized to quinone form by free radicals and protects Polyunsaturated fatty acids (PUFA ) from peroxidation reactions

4. STRUCTURE: • Structure of Vitamin E was explained by Paul Karr ( Noble prize-1937)

5. Properties of Vitamin E • Properties of Vitamin E are 1. Heat stable 2. Oxidation labile 3. Low molecular weight (453 Dalton) 4.Absorbs UV light (292nm) 5. Optically active 6.Forms salts with OH group of chromone ring (at 6 th position)

6. Sources: • The richest source is vegetable oils and nuts • Cabbage • Wheat germ oil • Fish liver oil is devoid of vit E

7. Category Recommended Dietary Allowance of Vitamin E • Recommended Dietary Allowance of Vitamin E Recommended Dietary Allowance of Vitamin E is 10 mg/day which is available in a normal diet. • 10mg of Tocopherol= 15 International Units • Requirement Vitamin E increases with higher intake of PUFA

8. ABSORPTION Vitamin E is absorbed along with fat in the upper small intestine Mechanism: • Vitamin E combines with Bile salts (micelles) to form mixed micelle and taken up by the mucosal cell • In the mucosal cell, it is incorporated into chylomicrons

9. TRANSPORT • Dietary vitamin E is incorporated to chylomicrons • In the circulation, chylomicrons transport vitamin E to the peripheral tissue or to the liver • Hepatic vitamin E is incorporated to VLDL • In the circulation, VLDL is converted LDL • Vitamin E is transported with LDL to reach the peripheral tissues including adipose tissue • Storage: Mainly stored in liver and adipose tissue • Present in biological membranes, because of its affinity to phospholipids

10. METABOLISM

11. Functions 1. Prevents sterility and closely associated with reproductive functions ( maintains germinal epithelium of gonads) 2. Essential for membrane structure and integrity of cell: a membrane antioxidant (vitamin E –lipophilic in nature) ,stored in a cell membrane along with lipoproteins and lipids prevents lipid peroxidation. 3.Protects RBC from hemolysis by free radicals 4. Enhances activity of δ aminolaevulinic acid (ALA) synthase and ALA dehydratase which Enhances heme synthesis 5.Protect liver from damaged by free radical 6.Useful for treatment of • Atherosclerosis • Muscle cramps • Cataract • Breast cancer

12. Antioxidant function of vit E R*=free radical, RH= inactivated free radical

13. Regulation of vit E • Dietary and supplemental vitamin E is absorbed and delivered to the liver, but of the various antioxidants with vitamin E activity, only α-tocopherol is preferentially recognized by the α-tocopherol transfer protein (α-TTP) and is transferred to plasma, while the other vitamin E forms are removed from the circulation • The liver is the master regulator of the body's vitamin E levels in that it not only controls α-tocopherol concentrations, but also appears to be the major site of vitamin E metabolism and excretion. • As a result of these various mechanisms, liver α-tocopherol and other vitamin E concentrations are closely regulated; thus, any potential adverse vitamin E effects are limited

14. Biosynthesis of vit E • Biosynthesis of tocopherol occurs in the plastids, except for the first steps that are initiated in the cytosol. • The aromatic headgroup of tocopherol comes from the shikimate pathway, p-hydroxyphenylpyruvate (HPP), derived from Tyrosine, is modified into homogentisic acid (HGA), by p-hydroxyphenylpyruvate dioxygenase (PDS1/HPPD) • The polyprenyl side chain, phytyl diphosphate (PDP), is derived from the MEP/DOXP pathway. • HGA and PDP are merged by HPT (homogentisatephytyl transferase (HPT), to 2-methyl-6- phytyl-1,4-benzoquinol (MPBQ). • MPBQ is methylated to 2,3-dimethyl-6-phytyl-1,4-benzoquinone (DMPBQ). • Tocopherol cyclase (TC) transforms both MPBQ and DMPBQ to γ- and δ-tocopherol, respectively. • Finally, γ- tocopherol methyltransferase (γ-TMT) catalyzes the conversion of γ- and δ-tocopherol to β- and α-tocopherol, respectively.

15. Biosynthesis of vit E

16. Deficiency • Generally deficiency is investigated by measuring plasma [Vitamin E]. • Deficiency results in: • Increase fragility of RBC • Premature aging • Varicose veins • Acne • Abetalipoproteinemia • Celiac spure

17. Hypervitaminosis E • toxicity at doses above 1000 IU • Administration of Vitamin E 300mg per day for 23 years that result in No toxic effects observed = LEAST TOXIC fat soluble vitamin

18. References Https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3997530/ https://www.ncbi.nlm.nih.gov/books/NBK173994/ • Harper’s Biochemistry 25th Edition • Text Book of Biochemistry-DM Vasudevan • ext Book of Biochemistry-Dr.U.Satyanarana