Vitamins II

VITAMIN C – ASCORBIC ACID    

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SYNTHESIS OF VITAMIN C URONIC PATHWAY

Anti –scorbutic vitamin Very sensitive to oxidation Rapidly destroyed by alkalines Drying vegetables usually result in loss of vitamin C Fruits in supermarket is more expensive compared to the ones sold in market is more expensive because it is refrigerated, it prevents the lost of vitamin c. if you placed the fruit on the table everyday it loses its vitamin c. Ordinary room temperature and heat destroys vitamin c. most easily destroyed among the vitamins. Take note of that And one more thing do not believe juices in tetra pack which has 100mg vitamin c. only magnolia has 100 mg vitamin c. Freezing has no deleterious effect. Strong reducing agents because its easily oxidized Pasteurizing milk destroys vitamin c In man we cannot synthesize vit. C it has to be taken in the diet. It is not stored Kailangan araw araw kasi even when you drink large doses today you’ll excrete it because its water soluble you don’t store it. Most important function of vitamin c is being COENZYME FOR COLLAGEN SYNTHESIS. When I lectured on carbo metab there ia a pathway which converts glucose to vitamin c, the URONIC ACID PATHWAY. The uronic pathway which converts glucose all the way to vitamin c, however in the pathway there is one step where in we don’t have the enzyme GULONOLACTONE OXIDASE. We don’t have these enzyme and so we cant convert our own glucose to vitamin c and so we have to take in vitamin c everyday.

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Dr. Remedios Santos Vitamins – Part II Medical Biochemistry B

If you take in large amount of oxalic acid you can form OXALIC ACID CRISTALS. Which can precipitate to the formation of OXALATE STONES. If you recall there is one vitamin that can give you oxalate stone when it is deficient vit B6. Large amount of vitamin c will also give you oxalate stone because the major storage form of vitamin c is oxalate.

PHYSIOLOGIC ROLE OF VITAMIN C 1. Hydroxylation of PROLINE and LYSINE to HYDROXYPROLINE and HYDROXYLYSINE, respectively. These are reaction important in collagen formation. Primary structure of collagen is GLY-x-y. wherein x and y may be any amino acid but majority of x and y is OHpro and OH lys. Repeated several times glycine is repeated every 3rd. these is important for the tensile strength without these abnormal collagen not as strong as it should be. It is found also in your blood vessel wall. So what is the most easily ruptured blood vessel it your CAPILLARY IN NOSTRIL . Early manifestation of vit c deficiency is frequent nosebleeding known as epistaxis. To rule out vitamin c deficiency give 2000mg for a week if bleeding does not improved rule out vitamin c deficiency. 2. Hydroxylation of tryptophan 3. Synthesis of norepinephrine

30 January 2012 transcribed for Medicine-1B nd 2 Semester SY 2011-2012

4. Tyrosine metabolism- vitamin c protects the enzyme that oxidize p-OH-phenyl-pyruvic acid. 5. Hydroxylation of steroids in the adrenal cortex 6. Serves as reductant of ferric to ferrous ion. Facilitates absorbtion and utilization of iron, also important in the transfer of iron thru transferring also involve in the mobilization of ironfrom its storage form ferritin. Iron in the diet are in ferric form it is important to be converted into ferrous form to be absorbed. 7. Involve in the convertion of folic acid to ACTIVE THFA (-)vitamin c will result to MEGALOBLASTIC type of anemia, folic acid deficiency.

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CLINICAL EFFECTS OF VITAMIN C DEFICIENCY SCURVY- usually manifested by bleeding gums and falling teeth.

8. Involved in the hydroxylation of Cholesterol to cholic acid.

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One way of excreting cholesterol from our body is thru bile acid.

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Acts as regulatory of cholesterol metabolism. Take 1000mg of vit. C before eating fatty foods to promote convertion to cholesterol / bile acid. It also prevents deposition of cholesterol to blood vessels. Vitamin c may play an important role in the reaction of the body to physiologic stress. Preventing many types of viral and bacterial infection by potentiating immune system. Prevents cancer metastasis by creating a wall over the cancer tumor so it wont spread. It inhibits HYALURODINASE which is needed for cell migration. Helps lower the incident of blood clot formation in veins. Helps prevents cancer causing causing substances principally the NITROSAMINE (salitre high in preserved and processed foods) Vitamin c is necessary for bone formation, since bone tissue has organic matrix containing collagen. -

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Anti cancer vitamins are ACE. Side effect of ascorbic acid is hyperacidity. To prevent this take it after meals Another side effect is oxalate stone to prevent these drink lots of water. Good sources of vitamin c are tomatoes and guavas.


Major function of vitamin c – coenzyme in the formation of tissue collagen or intracellular cement. At least 1 gram of vit. C has been shown to block the nitrosamines formation in the body. Basic deficiency in vitamin c is abnormal collagen formation.

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Gums are spongy , tender and easily bleed leading to infection, loosing the teeth and falling teeth. Poor wound healing because of weak collagen Decreased ability to combat infection Impairment of growth of bones and teeth. Easy fracturability of the bones may occur. Skin changes- roughening of skin because of hyperkeratenic papules. Purpura or hemorrhages of the skin especially on the areas subjected to trauma are noted. Vitamin c makes skin smooth. petechial, subcutaneous, subperiosteal and internal hemorrhage. Internal bleeding is due to fragility of blood vessel wall. Swelling at the end of of long bones and atcostochondrial junction this is called SCORBUTIC ROSARY. Edema, pallor, anemia Easy fatiguability, weakness, aching bones and joints and extremities. Defects in skeletal calcification without much disturbance in mineral metabolism

VITAMIN A Chemistry: Vitamin A is a polyisoprenoid compound containing a cyclohexenyl ring. It is stored as retinol esters in the liver Precursor of Vitamin A: 1. Alpha-carotene- 1 mole


2. Beta-carotene-BEST precursor because it has highest Vitamin A activity; yields two moles of retinol (Abundant in yellow fruits and vegetables) 3. Gamma-carotene- 1 mole 4. Cryptoxenthin Types of Vitamin A 1. Vitamin A-1 alcohol or retinol – predominates in saltwater fish 2. Vitamin A-2 or 3-dehydroretinol – predominates in freshwater fish; its potency is 40% that of vitamin A-1 3. Vitamin A aldehyde or retinol 4. Vitamin A acid or retinoic acid – least toxic because it is least stored and used by derma. (Synthetic form of vitamin A)

CONVERSION of Beta-carotene to different forms of Vitamin A – takes place primarily in the liver and some intestinal cell - Requires proteins

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FACTORS affecting absorption, transport and metabolism of vit A 1. Low intake of dietary fat- vit A needs fat to be absorbed 2. Inadequate protein and zinc intake- needs lipoprotein for transport 3. Vit E deficiency – for protection of Vit A so it wouldn’t be destroyed via oxidative reaction. Vit A is easily destroyed 4. Infection particularly acute hepatitis, measles, upper respiratory infections, chicken pox and bronchitis –double intake of VitA if children have infections 5. Chronic parasitic infestations

Physiologic Functions of Vitamin A 1. Role in the physiologic mechanism of vision – Rhodopsin that is needed to see in the dark is composed of Vitamin A and opsin. 2. Maintenance of the integrity of the epithelial tissues – salivary glands, tongue, pharynx, respiratory tract, genitourinary tract, eyes, etc. (Anti infective and anticancer vitamin 3. Because it is believed that the moistness of the epithelial lining prevents entry of infectious agents and carcinogens). In vit A deficiency, epithelial lining becomes dry and keratinized and will develop cracks and openings where infectious and carcinogenic agents enter. 4. Skin – dryness and roughness of the skin develops in Vitamin A deficiency – reffered to as toad skin (very rough like sandpaper) 5. Role in growth – failure of skeletal growth appears to reflect a defect in the synthesis of chondroitin sulfate, which has been reported be due to inability to make a phosphoadenosine phosphosulfate, the sulfate donor. 6. Retinol is also involved in the biosynthesis of mucopolysaccharides. 7. Role in reproduction - reproduction fails in vitamin A deficiency because of atrophy of germinal epithelium in males. In females, the normal estrous cycle is not maintained. Alterations in the lining of the reproductive tract appears to interfere with nutrition of the embryo 8. Development of bones and teeth.


9. Control of cell differentiation and turnover. This is one of the most important functions of Vitamin A All trans-retinoic acid and cis-retinoic acid regulate growth, development and tissue differentiation. Like the steroid hormones, retinoic binds to nuclear receptors that bind to response elements of DNA and regulate the transcription of specific genes

There are 2 Families of Nuclear retinoid receptors 1. Retinoic acid receptors (RARs)  Binds all trans-retinoic acid or 9-cis-retinoic acid 2. Retinoid X receptors (RXRs)  Binds 9-cis-retinoic acid

ANOTHER important function of Vitamin A  Vitamin A has an important role in differentiation of immune system cells and mild deficiency leads to increased susceptibility to infectious diseases. Furthermore, the synthesis of retinol-binding protein in response to infection is reduced, decreasing the circulating vit and therefore there is impairment of immune responses.

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CLINICAL Effects of Vitamin A Deficiency A. Eye manifestations  Early symptom – nyctalopia or night blindedness (inability to see in dim light) because there is no Vitamin a to combine with opsin. The Vitamin A needed is 11-cis retinal.  Photophobia  Xerosis conjunctivae – Bitot’s spots (foam like spots in conjunctivae either at lateral or medial side. Does not cause blindess unless it totally blocks vision. Reversible with high dose of Vitamin A)  Xerosis cornea - when dryness progresses to conea, ulcers develop. When ulcers develop, it will now be infected and will turn into soft jelly-like mass with pus and blood inside Keratomalacia)  Xeropthalmia – generalized dryness of eye tissues (all parts of the eyes dries up)  Corneal Ulcers may develop. – the whole cornea may be transformed to a soft jelly like mass – a condition called keratomalacia (cornea may rupture leading to blindness)  Blindness may result to opacities affecting the whole cornea or from perforation of the cornea which results in collapse of the eyeball. B. Epithelial cells in all structures undergo keratinizing metaplasia  Increased susceptibility to infection of respiratory tract  The cells of the kidney medulla may cornify and renal calculi forms  Ducts of glands may become blocked and glands atrophy  Atrophy of the germinal epithelium causes sterility in the male C. Cessation of Growth D. Skin manifestations  Dryness and scaliness  “toad skin” – hyperkeratotic papules


BITOT’S SPOTS: Xerosis conjunctivae Give high dose of vitamin A, 1 tablet of 100,000IU (5,000IU is vitamin A RDA)

METABOLISM OF VITAMIN D-3

KERATOMALACIA: Cornea is soft and jelly-like Easily rupture Contents of eyeballs come out when ruptured leading to blindness HYPERVITAMINOSIS A = Toxic to the liver and can cause hepatomegaly NEVER GIVE HIGH DOSE OF VITAMIN A DURINGPREGNANCY BECAUSE IT IS TOXIC TO THE FETUS AND CAN CAUSE CONGENITAL ANOMALY LIKE CNS PROBLEMS VITAMIN D Synonyms: Anti-rachitic vitamin; “Sunshine vitamin”

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-A fat soluble vitamin you can synthesize in the body from cholesterol

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Two forms of vitamin D which are of importance in human nutrition

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1. Vit D-2- Activated ergosterol; ergocalciferol; viosterol – of plant or vegetable origin 2. Vit D-3- activated 7-dehydrocholesterol; cholecalciferol – of animal origin; occurs in fish liver oils can be synthesized in the body from cholesterol.

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1,25- dihydroxycholecalciferol -

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7-dehydrocholesterol upon exposure to sunlight is converted to cholecalciferol. Cholecalciferol goes to the liver and undergoes hydroxylation to become 25-hydroxycholecalciferol (Calcidiol) the storage form of vit D in the liver. From the liver it goes to the kidneys. Another hydroxylation takes place to form 1,25dihydroxycholecalciferol (calcitriol). This is the form that helps in the absorption of Ca and P in the body which is the most important function of vit D. So to activate vit D, it has to undergo 2 steps of hydroxylation. First in the liver and second in the kidney

Most active form of vitamin D Also called CALCITRIOL Sometimes termed as the “hormone-form” of vitamin D. Also regarded as “calcium-mobilizing” hormone Its principal function is to maintain the plasma calcium concentration and it achieves this in 3 ways 1. It increases intestinal absorption of calcium 2. It reduces excretion of calcium by stimulating resorption in the distal renal tubules 3. It mobilizes bone mineralization


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Other functions of Calcitriol: Involved in insulin secretion Involved in the synthesis and secretion of parathyroid and thyroid hormones Involved in the inhibition of production of interleukin by activated T lymphocytes and immunoglobulin by activated B lymphocytes Differentiation of monocyte precursor cells Modulation of cell proliferation

24,25- dihydroxycholecalciferol -

Another active metabolite of Vit D-3 formed in the kidneys; less active than the 1,25dihydroxycholecalciferol

25-hydroxycholecalciferol- also called CALCIDIOL -

Major form of vitamin D in the circulation and the major storage in the liver

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CLINICAL EFFECTS OF VIT D DEFICIENCY Not common if you are exposed to adequate sunlight. Rickets- Vit D deficiency in children characterized by inadequate calcification of cartilage and bone. Bone becomes soft and pliable. This leads to: -

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PHYSIOLOGIC FUNCTIONS OF VITAMIN D Principal Role- to increase absorption of calcium and phosphorous in the intestines. -

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Produces an increase in the biosynthesis of calcium-binding proteins necessary for the mobilization and transport of calcium ions at the brush border side of the intestinal epithelium Increases mobilization of calcium from bones Influences the handling of phosphate by the kidney by increasing kidney tubular reabsorption of phosphate. Plays a role in citrate metabolism o Citrate is involved in the mobilization of minerals from bone tissue and removal of calcium from the blood. The removal of calcium results in an anticoagulant effect which gives Vit D a useful role in producing plasma and serum for medical use

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Vit D is required for normal growth in mammals

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Bowlegs and knock-knees Enlargement of the ends of bones Rachitic rosary- rows of bead like swellings at the rib junctions (swelling of costochondral junction) Contracted pelvis (Indication for caesarian. Size of pelvic cavity is not adequate for normal delivery of the baby) Delayed closure of the fontanelles (Normally there are 2 fontanelles the anterior and the posterior and must close within a year) Delayed tooth eruption (Normally tooth erupts at 6 months) Harrisons groove- a horizontal depression along the lower border of the thorax (below the last rib) corresponding to the costal insertion of the thorax seen in advanced rickets Caput quadratum- development of bosses on the temporal bones. (Head shape like a square)

Osteomalacia- Vit D deficiency in adults -

There is softening and weakening of the bones and this may lead to deformities and easy fracturability Serum calcium is reduced- this may lead to tetany

Tetany- Hypercitability of the nerves and muscle due to decreased concentration of calcium. Uncontrollable twitching of muscles -

Characterized by carpopedal spasm, muscular twitchings amd cramps, laryngospasm (makes speaking difficult), exaggeration of reflexes and choreiform movements (a wide variety of rapid,


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highly complex, jerky movements performed involuntarily). Twitching of the eye can be a sign of low level of calcium in the body If serum calcium is low for a long time, it would affect your heart. Abnormal twitching of the heart can lead to heart muscle fatigue causing it to suddenly stop. Leads to death.

VITAMIN E- Rejuvenating vitamin (anti-aging); (antisterility vitamin- rodents only) Precursors of Vitamin E (tocopherols): -

Alpha-tocopherols- most potent Beta tocopherol Gamma tocopherol Delta Tocopherol

One I.U. of vit E= 1mg of alpha tocopherol acetate -

The intake of PUFA is the single most important factor in the determination of the RDA of vit E. Food sources All green plants contain considerable amount of vegetable oils which are rich in vit E. Wheat germ oil has the highest concentration.

Vit E- Major lipid antioxidant in cell membranes and plasma lipoproteins -

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Its main function is as a chain-breaking, free radical trapping antioxidant in cell membranes and plasma lipoproteins. Vit E reacts with the lipid peroxide radicals formed by peroxidation of PUFA before they can establish a chain reaction. The tocopherol free radical product is relatively unreactive and ultimately forms nonradical compounds. When fats are subjected to lipid peroxidation, fatty acid peroxide is formed which is toxic After another round of lipid peroxidation, radicals are formed Radicals are carcinogenic agents (not only from foods but also in the environment. ex; pollutants in air. Cigarettes has 15 kinds of radicals in it)

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The more fats that you eat, the more radicals that you form, the more prone you are to cancer. People who love to eat fatty foods have 20-35% more chance to develop cancer The more fat that you eat, the higher is your vit E requirement to prevent lipid peroxidation Vit E is a radical scavenger (anti-cancer). It converts radicals to non-toxic substances.

PHYSIOLOGIC EFFECTS OF VITAMIN E 1. Antioxidant property- most striking chemical (most important) property. This is essentially true for its effects on fats a. Spares or protects vit A and carotenes from oxidative destruction b. Protects polyunsaturated fatty acids from oxidative destruction c. Inhibits damage to lung tissue from oxidants in the air- ozone, nitrogen dioxide and others. 2. Maintains integrity of the RBC membrane - Decreased vit E will result in increases susceptibility of RBC to hemolysis. (Deficiency leads to hemolytic anemia) 3. Maintains integrity of muscles (people with muscle dystrophy receive high dosage of vit E) 4. Together with selenium prevents liver necrosis - 25mcg of Se for each 200 units of vit E increases vit E’s potency 5. Gonadal and reproductive functions- in rodents only - Deficiency leads to degenerative changes in the seminiferous tubules epithelium; also leads to the development of placental abnormalities which interferes with the nutrition of the fetus. Anti-aging effect of vit E is also because of its anti-oxidant property. Radical Theory of Aging- Most accepted theory of aging. “The more radicals you are exposed to, the faster is your


aging process”. Because the radicals can make a lot of our biological pathways go wrong. CLINICAL EFFECTS OF VIT E DEFICIENCY In man- A magaloblastic type of anemia develops- due to increased hemolysis of red blood cells

If the mother has Vit K deficiency, the baby will also have deficiency.. and the baby will have hemorrhagic dse of the newborn.. After delivery, the baby with hemorrhagic disease will have a continuous internal bleeding from the nose, mouth and ears.

In animals- Failure of gestation in females -

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Testicular degeneration in males leading to permanent sterility Muscular dystrophy- degenerative changes in the muscles. Skeletal and smooth muscles leading to necrosis, edema, inflammation and fibrosis, then to weakness and paralysis. Changes in nervous tissue- changes lead to degeneration of nerve cells. Could be brought about by toxic action of fatty acid peroxides.

Vitamin K

There will also be bloody stool and urine, and the baby will develop hematoma due to ruptured blood vessels..

Physiologic roles of Vit. K:

1 Synthesis of prothrombin in the liver – Vit K is a cofactor in the gamma-carboylation of glutamic acid residues in several of the blood clotting factors. Deficiency will lead to a prolonged clotting time.

Coagulation vitamin -

Anti-Hemorrhagic vitamin Last one to be discovered

3 forms of Vitamin K:

1. Phylloquinone or vitamin K-1 - Major form of vit. K found in plants 2. Farnoquinone or vit. K-2 - found in putrid fish meal 3. Menadione or vit. K-3 - The parent compound of the vit. K series - Synthetic form of Vit K - This is the one that is injected to newborn babies to prevent Hemorrhagic dse of the newborn.

2. Synthesis of plasma clotting factors 2(prothrombin), 7, 9 , and 10.

All of these factors require a reaction called gamma carboxylation of glutamic acid.. these specific reaction needs vit K as coenzyme for synthesis of factors 2,7,9 and 10.

Absence of vit K means no formation of factors 2,7,9,10, so walang coagulation of blood… so maski small yung wound there can be cont bleeding from it.

(Vit K deficiency - no clotting factors – continous bleeding)

Menaquinones – synthesized by intestinal bacteria

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3.Component of Electron transport chain – in the form of Coenzyme Q

Coenzyme Q is needed for oxidative phosphorylation for energy.

You also need vit K to synthesize two calcium binding proteins: Osteocalcin and Bone matrix GLA CHON. – These proteins are important for binding of Ca, and they contain a gamma carboxyglutamuic a. residue.

So you also need vit K for gamma carboxylation of glutamic a. residue in osteocalcin and Bone matrix GLA CHON.

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Vitamins II

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