Sheet #12 Lecture (Vitamins 1 Lecture 2) Lecture Date :- 5-8-2018 Done By :- Dana Masoud Edited By :- Sima Shihab Doctor :- Nabil Amer

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Vitamin E Vitamin E is a family of α−, β−, γ−, δ− tocopherols and corresponding tocotrienols izomers. The highest biological activity has α-tocopherol.

Reduce the energy of the free radical What is it? Antioxidant Reduce the energy of the free radical Stop the free radical from forming in the first place Interrupt an oxidizing chain reaction to minimize the damage of free radicals

Vitamin E is the most important antioxidant because: SHEET P.1 Vitamin E is the most important antioxidant because: free radicals are very dangerous and can damage the cell membrane which can cause: haemolysis to the RBCs, aging and some cancers and many other problems within the cells. Some people use vitamin E as a precaution because it protects cell membranes and other fat soluble parts of the body.

EXTRA NOTES ON FREE RADICALS! What are free radicals and why do we need antioxidants??? Free radicals are atoms or groups of atoms with an odd (unpaired) number of electrons and can be formed when oxygen interacts with certain molecules. Once formed these highly reactive radicals can start a chain reaction, like dominoes. Their chief danger comes from the damage they can do when they react with important cellular components such as DNA, or the cell membrane. Cells may function poorly or die if this occurs. To prevent free radical damage the body has a defense system of antioxidants. Antioxidants are molecules which can safely interact with free radicals and terminate the chain reaction before vital molecules are damaged. Although there are several enzyme systems within the body that scavenge free radicals, the principle micronutrient (vitamin) antioxidants are vitamin E, beta-carotene, and vitamin C. Additionally, selenium, a trace metal that is required for proper function of one of the body's antioxidant enzyme systems, is sometimes included in this category. The body cannot manufacture these micronutrients so they must be supplied in the diet.

What does it do? Protects cell membranes and other fat-soluble parts of the body (LDL cholesterol) from oxidation May reduce the risk of heart disease May also discourage development of some types of cancer Promotes normal growth and development Promotes normal red blood cell formation Acts as anti-blood clotting agent Plays some role in the body’s ability to process glucose Also been known to aid the process of wound healing

SHEET P.2 (Oxidized/modified LDL) is dangerous causing heart attacks and malfunctions, not the (LDL) on its own which carries cholesterol to all the organs of the body. Vitamin E acts as an anti-blood clotting agent, the opposite to prostaglandins.

RDA: recommended daily amount Heart disease: Two studies published in the New England Journal of Medicine by Harvard researchers Of 127,000 health professionals, those who took large doses of Vitamin E had a 40% lower risk of heart disease. Taking more than RDA of vitamin E improves the immune system in the elderly. RDA: recommended daily amount

* Hypervitaminosis = vitamin toxicity SHEET P.3 Vitamin E is good to be taken in excess regularly as it won’t be toxic, it is one of the fat soluble vitamins that don’t cause toxicity, as opposed to both vitamins A & B which can be toxic. Vitamin A: (A Vitaminosis/ A Hypervitaminosis), excess vitamin A will be stored in the lipids/adipose tissue. * Hypervitaminosis = vitamin toxicity

Sources of vitamin E fortified cereals seeds and seed oils, like sunflower nuts and nut oils, like almonds and hazelnuts green leafy vegetables, broccoli cabbage celery egg yolk http://health.allrefer.com/health/nutrition.html

Vitamin E Recommended Daily Allowances (RDA): Children 0-12 months 3-4 mg 9-12 IU 1-7 years 6-7 mg 15-21 IU 11-18 8 mg 24 IU Males 18+ 10 mg 30 IU Females 18+ 8 mg 24 IU pregnant 12 mg lactating 11 mg These requirements always increase in pregnancy. ‼ You don’t have to memorize these, just have a general idea.

Who is likely to be deficient? Severe vitamin E deficiencies are rare Lack of vitality Lethargy Apathy Inability to concentrate Muscle weakness

Who should take supplements? People over the age of 55 Smokers People who abuse alcohol Anyone with inadequate caloric or nutritional dietary intake or increased nutritional requirements

SHEET P.4 Usually old people are in need of taking extra vitamins, but if they eat well and are in good health they won’t need any excess. Smokers always have low Vitamin E and deficiency in a lot of things in general.

Miscellaneous: Freezing may destroy Vitamin E Extreme heat causes Vitamin E to break down Avoid deep-fat frying foods that are natural sources of Vitamin E Reduces potential toxicity of Vitamin A - Excessive doses causes Vitamin A depletion

Excess vitamin E causes decreasing of vitamin A SHEET P.5 Excess vitamin E causes decreasing of vitamin A

Vitamin E Adsorbtion from the small intestine. Its absorption is dependent on the presence of lipids in the diet. Associated with plasma lipoproteins → liver uptake through receptors for apolipoprotein E. α−tocopherol is bind to α-tocopherol transport protein (α-TTP) → transported to the target organs (the excess is stored in adipocytes, in muscle, liver). β−, γ− a δ−tocopherols are transferred into the bile and degraded. Which means it goes down with lipids like any other

Vitamin E as antioxidant Stops free radical reactions (peroxyl radicals ROO∙ , oxygen radicals HO∙, lipoperoxid radicals LOO∙). Chroman ring with OH group → uptake radicals. Here vitamin E acts as an antioxidant

*ROS=reactive oxidant species SHEET P.6 Vitamin E is a fat-soluble antioxidant that stops the production of ROS formed when fat undergoes oxidation. *ROS=reactive oxidant species Cool fact: Scientists are investigating whether, by limiting free-radical production and possibly through other mechanisms, vitamin E might help prevent or delay the chronic diseases associated with free radicals.

These are very important and they exist in every cell in our body Interaction and synergism between antioxidant systems operating in the lipid phase (membranes) and the aqueous phase (cytosol) PUFA-H = polyunsaturated fatty acid PUFA-OO∙ = peroxyl radical of polyunsaturated fatty acid PUFA-OOH = hydroxyperoxy polyunsaturated fatty acid PUFA-OH = hydroxy polyunsaturated f.a. Free radical chain reaction These are very important and they exist in every cell in our body

 degrade H₂O₂ (toxic) to Water & Oxygen SHEET P.7 Glutathione peroxidase, catalase, and superoxide dismutase are all important antioxidants found in all body cells  degrade H₂O₂ (toxic) to Water & Oxygen Later on we’ll take what causes a deficiency in those, which makes Glutathione change from the reduced form to the oxidised, and therefore cause degradation of RBCs, haemolysis, and anaemia which is called Glucose-6-Phosphate deficiency anaemia (أو مرض التفول) due to the deficiency in the enzyme Glucose-6-Phosphate Dehydrogenase. Glutathione Peroxidase requires Selenium (Se) –a trace element. We mentioned 3 Trace Elements thus far: Calcium (Ca), Iron (Fe), and Selenium (Se). There are 14 important trace elements, and all of them exist inside the cells. Recall: Potassium, Sodium, Bicarbonate, Chloride are electrolytes.

SHEET P.8

Vitamin E as enzyme cofactor α-tocopherol quinon generated by oxidation of α-tocopherol can acts as a cofactor of mitochondrial unsaturated fatty acids . α-tocopherol quinon + cytochrom B5 + NADH+H+ initiate formation of double bonds in FA – temporarily changes to α-tocopherol- hydroquinon (in the presence of O2 changes back to α-tocopherol quinon). co = helping agent

Cofactors = metal ions (eg. Mg⁺⁺, Zn ⁺⁺, Ca ⁺⁺, Mn ⁺⁺) SHEET P.9 Cofactors = metal ions (eg. Mg⁺⁺, Zn ⁺⁺, Ca ⁺⁺, Mn ⁺⁺)

Vitamin E – deficiency and toxicity The lack of α-tocopherol in plasma is often associated with impaired fat absorption or distribution (in patients with cystic fibrosis, in patients with intestine resection) Deficiency of vit. E exhibit - neurological problems, impaired vision, eye muscle paralysis, platelet aggregation, impairment of fertility in men, impaired immunity. Toxicity is relatively small. Extra note: intestine resection is a surgery to remove any part of the bowel

SHEET P.10 Cystic fibrosis: is a genetic disorder that affects mostly the lungs, but also the pancreas, liver, kidneys, and intestine. Caused by (mutation) in a gene that affects/changes Sodium and chloride channels, leads to thickened mucus aggregation, bacterial infection, & difficulty in breathing. It’s a genetic disease causing a deficiency of the trans membrane cystic fibrosis receptor, which exchanges sodium chloride, leads to accumulation of sodium chloride, causing dry mucus, and increased infections.

Vitamin K Vitamin K is a group of lipophilic, hydrophobic vitamins. They are needed for the postranslation modification of proteins required for blood coagulation, They are involved in metabolism pathways, in bone mineralisation, cell growth, metabolism of blood vessel wall. Without vitamin K, blood coagulation is seriously impaired

Vitamin K Vitamin K1 (phylloquinon) – plant origin Vitamin K2 (menaquinon) – normally produced by bacteria in the large intestine K1 a K2 are used differently in the body K1 – used mainly for blood clotting K2 – important in non- coagulation actions - as in metabolism and bone mineralization, in cell growth, metabolism of blood vessel walls cells. Vitamin K1 Vitamin K2 Synthetic derivatives of Vit.K

SHEET P.11 Some vitamins are produced by the bacteria in the intestinal flora, such as vitamin K. That’s why when there’s an infection in the intestines and we take antibiotics, we must also take vitamin K, unless the antibiotic already came with vitamin K pre-added to it.

Sources of vitamin K Green leafy vegetables vegetable oil broccoli cereals http://health.allrefer.com/health/nutrition.html

Vitamin K - function Cofactor of liver microsomal carboxylase which carboxylates glutamate residues to γ-carboxyglutamate during synthesis of prothrombin and coagulation factors VII, IX a X (posttranslation reaction). Carboxylated glutamate chelates Ca2+ ions, permitting the binding of blood clotting proteins to membranes. Forms the binding site for Ca2+ also in other proteins – osteocalcin.

Osteocalcin is formed in all bone cells. SHEET P.12 Osteocalcin is formed in all bone cells. Blood clotting requires calcium, and vitamin K. Extra notes: Osteocalcin : is a noncollagenous protein hormone found in bone and dentin. Because it has gla domains, its synthesis is vitamin K dependent *gla domain: Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain  

warfarin (-) farin

Warfarin (like Heparin) is an anticoagulant (blood thinner). SHEET P.13 Warfarin (like Heparin) is an anticoagulant (blood thinner). Heparin is naturally produced by the body, while warfarin is not (it is a drug). Warfarin inhibits the formation of modified prothrombin & γ-carboxyglutamate from prothrombin, and therefore prevents blood clotting. Warfarin comes in different tablet doses; 5 mg, 7.5 mg, 10 mg. To control the warfarin dose, we perform coagulation tests called Prothrombin Time (PT)/Partial Thromboplastin Time (PTT), to determine the warfarin level the patient was taking, and to keep it within a certain level so their blood will neither coagulate nor become diluted.

Vitamin K - deficiency Deficiency is caused by fat malabsorption or by the liver failure. Blood clotting disorders – dangerous in newborns, life-threatening bleeding (hemorrhagic disease of the newborn). Osteoporosis due to failed carboxylation of osteocalcin and decreased activity of osteoblasts. Under normal circumstances there is not a shortage, vit. K is abundant in the diet.

Osteoblasts = bone-forming cells. Osteoclasts = bone-eating cells. SHEET P.14 Recall: any defect in fat absorption leads to a deficiency in a fat-soluble vitamin. Steatorrhea=fatty stools; fat malabsorption causes diarrhoea due to the increase of fat content in the stool, due to a defect in bile…etc Osteoblasts = bone-forming cells. Osteoclasts = bone-eating cells. Osteocytes = bone cells with neurons.

Vitamin K can be made by intestinal bacteria. Sources of Vitamin K Vitamin K can be made by intestinal bacteria. Newborns are given a dose of vitamin K at birth.

Caloric Content of Foods Concepts of Physical Fitness 12e McGraw Hill - www.mhhe.com/phys_fit Caloric Content of Foods Carbohydrates 4 cal/g Protein 4 cal/g Fats 9 cal/g Alcohol 7 cal/g This slide shows the calorie content of different food stuffs Concept 16

The Vitamin Game