vitamin e

Vitamin E : Vitamin E It is a naturally occurring antioxidant and anti sterility vitamin

Dietary source : Dietary source Vegetable oils are rich source, wheat gram oil peanut oil, corn and sunflower oil.

RDA : RDA 10 mg for men, 8mg for women 1mg=1.5IU

Chromanol ring with Side chain Tocopherols contain 3 asymmetric centers: at the # 2position of chromanol ring and the # 4 and # 8 positions onthe phytyl side chain : Chromanol ring with Side chain Tocopherols contain 3 asymmetric centers: at the # 2position of chromanol ring and the # 4 and # 8 positions onthe phytyl side chain α-tochopherol

Two class of tocopherols : Two class of tocopherols • These vitamers can be put into 2 classes: The tocopherols (saturated phytyl side chain) The tocotrienols (unsaturated phytyl side chain with 3 double bonds) maximum absorption at 294nm antioxidant property is due to the presence of the chrome ring.

Structure of a-tocopherol : Structure of a-tocopherol

Digestion and Absorption of Vitamin E : Digestion and Absorption of Vitamin E Dietary vitamin E primarily consists of α and γ-tocopherols, of which approximately 20-50% is normally absorbed. Vitamin E is absorbed with fat and must be emulsified first with bile from the liver. Vitamin E esters in the diet are hydrolyzed by pancreatic and intestinal mucosal esterases before absorption. Vitamin E is absorbed into the intestinal mucosal cell by a non-carrier-mediated process (passive diffusion).

Transport of Vitamin E : Transport of Vitamin E After absorption, vitamin E is transported in chylomicrons, and most of the vitamin E (both α and γ-tocopherols) returns to the liver in chylomicron remnants. In the hepatocyte, vitamin E is released from chylomicron remnants and bound by a α –tocohpherol transfer protein in cytosol, and then transferred to the endoplasmic reticulum for packaging into VLDL(similar to fat transport).

Vitamin E & Vitamin K absorption : Vitamin E & Vitamin K absorption Absorption of vitamin E & vitamin k with fats

Transport of chylomicrons : Transport of chylomicrons Inside the enterocyte, tocopherols are incorporated into “chylomicrons” and transported via the lymph and thoracic duct into systemic circulation. Any problem in the pancreas that decreases pancreatic enzyme concentration e.g. cystic fibrosis can result in vitamin E malabsorption. Any disease that reduces the surface area of intestinal cells (e.g. celiac disease) or the total length of the intestine can result in vitamin E malabsorption.

Cont.. : Cont.. Tocopherol is distributed to tissues primarily by LDLs and may play a role in protecting LDLs from oxidation.

Storage of Vitamin E : Storage of Vitamin E There no single storage organ for vitaminE. The largest amount is concentrated in adipose tissue with smaller amounts in liver, muscle lung, heart and adrenal gland. Adipose tissues are long-term storage place of vitamin E. VitaminE accumulates slowly and is also released slowly from adipose tissues. • The liver functions as a rapid turnover store of vitamin E, therefore, large amounts of vitamin E are not accumulated there .The amount of vitamin E in the liver is an index of dietary intake.

Routes of Excretion : Routes of Excretion Unlike other fat-soluble vitamins, vitamin E is not accumulated in the liver to toxic levels, suggesting that excretion and metabolism are important in preventing adverse vitamin E effects. The primary oxidation product of α-tocopherol is α-tocopheryl quinone, which can be conjugated to yield α-tocopheryl glucuronate . α-tocopheryl glucuronate can be excreted into bile or further degraded in the kidneys to α-tocopheronic acid, which is excreted in the urine. And mainly excreted in feces via hepato biliary route.

Anti oxidant property of vitamin E : Anti oxidant property of vitamin E

Functions of vitamin E : Functions of vitamin E Vitamin E is essential for the membrane structure and integrity of the cell, hence it is regarded as it is the membrane antioxidant. It prevents the per oxidation of polyunsaturated fatty acids in various tissues and membrane. it protects RBC from hemolysis by oxidizing agents. It is closely associated with reproductive functions and prevents sterility. vitaminE preserves and maintains germinal epithelium of gonads for proper reproductive function

Slide 16 : It increase the synthesis of heme by enhancing the activity of enzyme ALA synthesis and ALA dehydratase in presence of pyridoxal phosphate.and is the rate limiting step in heme synthesis. Vitamin E with selenium The principal function of vitamin E is maintenance of cell membrane integrity

Slide 17 : The mechanism by which vitamin E functions to protect the membranes is through its ability to prevent the oxidation of unsaturated fatty acids contained in phospholipids of the cellular membranes. Vitamin E is a biological antioxidant and can act as a “scavenger” of free radicals, thus protecting cell membranes from the oxidative destruction by free radicals. Free radicals are highly reactive, and can damage polyunsaturated fatty acids and protein constituents in the cell membranes.

Slide 18 : Tissues with cell membranes especially susceptible to oxidation include the lungs, brain, and RBC Reactive oxygen species and other “free radicals”are normally formed by several cellular enzyme systems, mitochondrial electron transport, and exposure to various environmental factors. Free radicals and oxidants are continuously generated within cells but are normally neutralized by the body’s antioxidant metabolism

Role of gluthaione : Role of gluthaione By reacting with the free radical the vitamin E which is in the reduced state is converted in tocopherol radical which is brought back by vitamin c or gluthione.

Functional activity : Functional activity Due to this functional relationship between vitamin E and unsaturated fatty acids, the requirement for vitamin E is dependent upon the amount of PUFA consumed. Oxidized LDL appears to initiate atheriosclerosis , and vitamin E protects LDL from oxidation by preventing the propagation initiated by free radical attack

Oxidation of LDL : Oxidation of LDL ROS/RNS pro-anthrogenic Oxd LDL LDL

Free radicals : Free radicals Vitamin E in humans protects the nervous system skeletal system, muscle and retina from oxidative damage. Oxidative stress can damage lipids, proteins, and DNA, Recent evidence suggest that oxidative stress plays a role in the pathogenesis of cancer. Cellular generation of hydroxy radical (.OH), superoxide radical (O2-) or hydrogen peroxide (H2O2) can initiate free radical-mediated lipid peroxidation in the exposed cell membranes.

Vitamin E Deficiency : Vitamin E Deficiency In unusual clinical circumstances e.g. individuals with alterations in intestinal absorption of dietary fat are predisposed to vitamin E malabsorption and subsequent deficiency. Genetic deficiency-in the function of the a-tocopherol transfer proteins .

Vitamin E deficiency : Vitamin E deficiency There are 3 categories of patients who are susceptible to vitamin E deficiency: 1) premature infants 2) patients with G.I. diseases leading to malabsorption (e.g. cystic fibrosis) 3) individuals with abetalipoproteinemia

symptoms : symptoms 1.opthalmoplegia 2 pigmented retinopathy are symptoms of vitamin E deficiency

Laboratory diagnosis : Laboratory diagnosis Vitamin E deficiency is made on the basis of low blood levels of a-tocopherol. The reference is made with the serum level Vitamin E 0.1-0.5 mg/DL Test to find HPLC

Toxicity and Treatment : Toxicity and Treatment Vitamin E appears to be one of the least toxic of the vitamin. Large intakes of vitamin E > 1200 mg /day.

Vitamin K : Vitamin K 1. only fat soluble vitamin with specific coenzyme function. 2.it is necessary for the production of blood clotting factors and essential for coagulation.

Dietary sources and RDA : Dietary sources and RDA Cabbage, cauliflower ,tomatoes,green vegetables, also egg,meat liver, cheese and dairy products RDA- 90ug/day for women 120ug/day for men Half of the body requirement is provided in the diet, while the other half is met from the bacterial synthesis.

chemistry : chemistry The naturally occurring forms of the vitamin are: Phylloquinone isolated from plants. Several menaquinones (K2) are synthesized by bacteria and found in animal products. Menadione (K3) which is not found naturally but is a common synthetic form of the vitamin.

Structure of vitamin K : Structure of vitamin K

Absorption of vitamin : Absorption of vitamin Phylloquinone is absorbed in the small intestine but are energy dependent. Menaquinones and synthetic menadione are absorbed from the distal ileum and the colon by passive diffusion. Menaquinones synthesized by bacteria in the lower G I tract can also be absorbed.

Absorption : Absorption Normal persons may absorb 40-80% of dietary vitamin K. But with impaired fat absorption as little as 20-30% of ingested vitamin K is absorbed. Absorbed vitamin K becomes part of the chylomicrons and is carried to tissues. Chylomicron remnants deliver vitamin K to the liver. In the liver this vitamin is incorporated into VLDLs and carried to tissues via LDLs. Vitamin K is concentrated in the liver, but has short half life, so very little long term storage occurs in this organ. Vitamin K is stored in in high quantities in adrenal glands, kidneys and bone marrow.

Absorption of vitamin : Absorption of vitamin

Functions and Mechanism Of Action : Functions and Mechanism Of Action This antihemorrhagic vitamin is necessary for the synthesis of 4 of the 13 factors needed for normal blood clotting (factors II or prothrombin, VII, IX and X). (Prothrombin------->Thrombin) Thrombin catalyzes the conversion of soluble fibrinogen to insoluble fibrin. Fibrin is needed for blood clotting.

Action of vitamin k : Action of vitamin k

Functions : Functions Blood clotting Blood clotting proteins called “vitamin K dependent proteins” contain glutamic acid residues, which must be carboxylated for the proteins to be activated. Vitamin K is needed for hemostasis because it acts as a coenzyme for the enzyme “ gamma glutamyl carboxylase” needed for converting specific precursor proteins to their active (carboxylated) form

Vitamin K dependent activity : Vitamin K dependent activity

Vitamin K cycle : Vitamin K cycle For the cycle to begin reduction of vitamin K quinone to the active hydroquinone (KH2) is necessary. Hydroquinone is needed for the activation of carboxylation enzymes.

Vitamin K cycle : Vitamin K cycle + ca

Inhibitors : Inhibitors dicoumarol and warfarin are anticoagulants that antagonize the action of the vitamin K Warfarin, interferes with the dithiol-catalyzed quinone reductase necessary for converting vitamin K to KH2. Warfarin may also act on the epoxide reductase preventing KH2 regeneration. The NADPH quinone reductase is relatively insensitive to warfarin.

Slide 42 : Two vitamin K dependent proteins in skeletal tissues include bone Gla protein or Osteocalcin and matrix Gla protein Osteocalcin, secreted by osteoblasts, is found in bone and dentine. After carboxylation involving vitamin K, the Gla residues facilitate the binding of calcium ions.

Role of vitamin k in gla protein : Role of vitamin k in gla protein

Deficiency : Deficiency Newborn infants and people who have been injured, or treated chronically with antibiotics are at risk for vitamin K deficiency. New-borns are at risk because milk is low in vitamin K and because intestinal bacteria in G.I. tract is not yet populated by “vitamin K synthesizing bacteria”. The fat soluble vitamins A and E are known as vitamin K antagonists. Prolonged sulfa and antibiotic therapy can cause destruction of G.I. tract bacteria that synthesize vitamin K .

Vitamin K affects clotting : Vitamin K affects clotting Deficiency of vitaminK leads to the lack of active prothrombin in the circulation. The result is that blood coagulation is adversely. Affected. The individual bleeds profusely even for minor injuries. The blood clotting time is increased., hemolytic anemia , jaundice .

diagnosis : diagnosis Is based on the elevated prothrombin level,or reduced clotting factor it is measured by HPLC Reference interval for plasma vitamin K is 0.13-1.19 ng/mL

reference : reference Harpers biochemistry-14 th edition Vasudevan-text book of biochem-4th edition HARRISON’S principle Of Internal medicine 17th edition Lehninger biochemistry. Lippincott’s biochemistry 3rd edition TIETZ textbook of clinical biochemistry -4th edition.