7. VITAMINS

1. 7. VITAMINS Medical Biochemistry Molecular Principles of Structural Organization of Cells

2. Vitamins are low molecular organic compounds, indispensable for the normal vital activity of the organisms • The vitamin compounds are classified in • Vitamins • Vitaminoids – similar as function but required in larger amounts • The same compound may be a vitamin for some organisms and an ordinary substance for others (ascorbic acid is a vitamin for human and guinea-pigs since it is not synthesized in their organism and not in rat, rabbit, dog) • Functions: • Take part in the production of coenzymes • Indispensible for the activity of the coenzymes • Regulators of biochemical processes

3. Vit name Chemical name Chemical forms Physiological name Biologically inactive Biologically active Derivatives Coenzymes B1 Thiamine Thiamine Thiamine diphosphate Thiamine triphosphate aneuritic B2 Riboflavin FMN, FMNH2 FAD, FADH2 growth factor B3 Pantothenic acid Pantothenate Pantotheine-4-phosphate CoA-SH B5(PP) Niacin Nicotinamide, Nicotinic acid NAD+, NADH+H+, NADP+, NADPH+H+ antipellagric B6 Pyridoxine Pyridoxine, Pyridoxol Pyridoxamine PALP, PAMP antidermatitis B9 (Bc) Folacin (folic acid) Folacin Tetrahydrofolic acid (TH4) and derivatives with 1 carbon radicals growth factor B12 Cyanocobalamin Cyancobalamin Oxocobalamin Methylcobalamin deoxyadenosylcobalamin antianemic C Ascorbic acid Dehydroascorbic acid Ascorbic acid antiscorbutic H Biotin Biotin Carboxybiotin antiseborrheic B4 Choline Choline Phosphocholine P Bioflavonoids Flavines: rutin, quercetin Flavonones: hesterindin, catechol complex vasoformatives B8 Inositol Inositol, mesoinositol N Lipoic acid Lipoic acid lipamide (oxidized and reduced) BT Carnitine Carnitine, Acylcarnitine B13 Orotic acid Orotic acid Orotodin-5-phosphate growth factor B15 Pangamic acid Pangamic acid antianoxic U S-methylmethionine S-methyl-methionine Methylthioaminosulphonium antiulcerous H Para-amino-benzoic acid (PABA) Para-amino-benzoic acid (PABA) Folic acid Microbial vitamin CLASSIFICATION 1. WATER-SOLUBLE VITAMINS

4. Vit name Chemical name Chemical forms Physiological name Biologically inactive Biologically active Derivatives Coenzymes A Retinol Retinyl acetate Retinyl palmitate Retinal, retinol, retinoic acid antixeroftalmic D Calciferols Ergocalciferol (D2) Cholecalciferol (D3) 1,25-dihydroxy-calciferol antirahitic E Tocoferols α,β,γ,δ –tocoferols, tocotrienols antisterilic K Naphtoquinones Phylloquinones(K1) Menaquinone (K2) antihemorrhage F Essential fatty acids Linoleic acid, linolenic acid, arachidonic acid Ubiquinone (coenzyme Q) Ubiquinone (CoQ) Ubiquinol (CoQH2) CLASSIFICATION 2. FAT-SOLUBLE VITAMINS

5. Vitamin Coenzyme form Type of catalyzed reaction Chemical group B2 Riboflavin FAD, FMN Oxydoreduction (H transfer) H (electrons) PP Niacin NAD+, NADP+ Oxydoreduction (H transfer) H (electrons) B1 Thiamin T-PP Acyl group transfer Aldehyde group transfer Decarboxylation of ketoacids R-CO- R-CO-COOH Lipoic acid T-PP-LSS Acyl group transfer Decarboxylation of ketoacids R-CO- R-CO-COOH B3 Pantothenic acid CoA-SH Acyl group carrier and transfer R-COOH, R-CO- B6 Pyridoxine PALP, PAMP Aminogroup transfer R-CHNH2-COOH Biotin Biotin, biocytin Carboxyl group removal or transfer COO-, CO2 Folic acid FH2, FH4 One-carbon group transfer -CH3, -CHO Vitamin B12 Coenzyme B12 Shift of H adjacent C Methyl group transfer -CH3 Ascorbic acid Uncertain, may serve as cofactor in hydroxylation reaction WATER-SOLUBLE VITAMINS AND THEIR COENZYMES

6. VITAMIN SOURCE • Source: • Food intake • Synthesis in the intestin - bacteria • In the organism, the vitamins may exist as • active vitamins or • provitamins which need a transformation in the organism in order to become active; for example: • Carotenes are provitamins of vitamin A; they are oxidized in the intestinal mucosa, with the participation of carotene dehydrogenase, to generate vitamin A • Derivatives of sterols are provitamins of vitamin D: • ergosterol  ergocalciferol (vit D2); • cholesterol  7-dehydrocholesterol  cholecalciferol (vit D3) • The vitamins and provitamins are transported to different organs and tissues where they perform their biochemical and physiological function • They may be accumulated in different organs

7. VITAMIN BALANCE • DEFICIENCY (negative balance) • Partial deficiency = hypovitaminosis • 1 vitamin deficiency = monohypovitaminosis • More vitamins deficiency = polyhypovitaminosis • Extreme deficiency = avitaminosis Hypovitaminosis manifest in a retarded growth of the young organisms, with specific intrinsic symptoms for each vitamin deficiency. Causes: • Exogeneous factors: • Unbalanced diet • Dysbacterioses after antibiotics, chemotherapeutic agents • Endogeneous factors: • Disorder in the absorbtion or transport of the vitamin, formation of the coenzyme (genetic defects of the synthesis of the apoenzyme or enzyme) • Increased vitamin catabolism • High requirements (pregnancy, growing organisms)

8. Vitamin Daily requirement Deficiency symptoms Fat soluble vitamins A retinal 1.0 mg Night blindness, xerophtalmia D calciferol 5 μg (synthesis in skin) Rickets, osteomalacia E tocopherols 10 mg Muscle weakness, hemolysis K menaquinone 1.4 mg (synthesis by intestinal bacteria Delayed blood coagulation Q ubiquinone Synthesis in the body Water soluble vitamins B1 thiamine 1.4 mg Polyneuritis (beriberi) B2 riboflavin 1.7 mg Dermatitis B3 pantothenic acid 7 mg Paresthesias, cramps in extremities B5 (PP) niacin 18 mg (synthesis in the body from tryptophan) Pelagra B9 folacin 0.4 mg Megaloblastic anemia Pteridine (biopterin) Synthesis in the body B6 pyridoxal 2.2 mg Dermatitis, psychic disorders B12 cobalamin 3 μg Anemia, neuropathy C ascorbic acid 60 mg Scurvy H biotin 0.15 mg (synthesis in the body by intestinal bacteria) Dermatitis

9. VITAMIN BALANCE • EXCESS (positive balance) =hypervitaminosis • Symptoms • Loss of apetite • Headache • Disorders of the gastrointestinal tract • High excitability of the nervous system • Hair loss • Skin desquamation • May lead to fatal outcome • Causes: • Excessive intake of food rich ina fat-soluble vitamin (liver of whale and polar bear rich in vit A) • Prescription of high doses of vitamin

10. ANTIVITAMINS • Are structural analogues: their structure looks like the structure of vitamin • They act as antagonists, inhibiting or blocking the activity of the vitamin as coenzyme, thus the physiological processes are disturbed • They produce symptoms as the vitamin deficiency does • Examples: • Antibiotics • Sulfonamides • Enzymes( ascorbase acts on ascorbic acid, tiaminase on thiamine, lipoxygenase oxidize the provitamin A)

11. WATER SOLUBLE VITAMINS • Complex B - General features • soluble in water • coenzymes in biochemical processes of great importance • activators - stimulate metabolic processes and regulate them • growth factors for microorganisms and young organisms • the most of them are synthesized by intestinal microflora (thiamine, pantothenic acid, nicotinamide, pyridoxine, folacine, corinoids, PABA) • Complex C: ascorbic acid, flavonoids (C2)

12. WATER SOLUBLE VITAMINSTHIAMINE, VITAMIN B1 • Source: plants (coarse bread, pea, beans) and meat products • Active form: thiamine diphosphate (T-PP) • Daily requirement: 1-3 mg • Structure: • Metabolism: dietary thiamine is hydrolyzed to free thiamine, which is absorbed in the intestine by diffusion; transported through the portal vein to the liver where is phosphorylated to thiamine-diphosphate (TDP, T-PP) or thiamine triphosphate (TTP); a part of the free thiamine is transported to tissues where it is phosphorylated. • In the cells T-PP is bound to the enzyme or stored in the muscles, intestine, liver. • When the coenzyme is broken down, the free thiamine is released, passes in the blood and is excreted in urine. • In tissues, TTP is formed from T-PP and ATP; it is involved in the neuron conduction and transmission of the nervous impulse

13. Biochemical functions: • TPP facilitates the mitochondrial oxydation of pyruvate and 2-oxiglutarate (energy generation from carbohydrates and aminoacids) • Essential in all processes that use NADPH+H+: • synthesis of fatty acids and sterols, • synthesis of nucleotides, nucleic acids, nucleotide coenzymes, • detoxification of drugs and toxins. • Defficiency = BERI-BERI: metabolism disturbances (catabolic processes are prevalent) and impaired functions of digestive, cardiovascular and nervous system: • loss of appetite, reduced secretion of gastric juice, diarrhea; • reduced contractility of muscles, myocardium, smooth muscles • decrease of peripheral sensibility, reflexes, neuralgia, impaired higher nervous activity Frequent in chronic alcohol addicts • Practical application: help the carbohydrates assimilation in diabetes mellitus, hypovitaminoses, dystrophy of heart,and skeletal muscles, inflammation of the peripheral nerves

14. RIBOFLAVIN, VITAMIN B2 • Source: liver, kidney, eggyolk, cheese and intestinal microflora • Daily requirements: 1-3 mg • Structure • Metabolism: • in food is present as FMN, FAD bound to protein or free in microorganisms; • in the intestine it is released and absorbed by simple diffusion; • used to synthesize FMN and FAD and flavin coenzymes • flavoproteins are catabolyzed to free riboflavin, excreted in urine. FMN FAD

15. Biochemical functions: • transfer of electrons and H+ in the respiratory chain • mitochondrial oxidation of pyruvate, succinate, 2-oxoglutarate, -glycero phosphate • oxydation of biogenic amines, aldehydes. • Defficiency: • lessions of the cornea, conjunctiva dry and inflammated, • mucosa of lips red, dried, craked, • skin desquamating • Practical application: • treating inflammation of skin, cornea, conjunctiva: dermatitis, poor healable wounds and ulcers of skin, keratitis, conjunctivitis • treating intoxication with CO, • medication of liver, muscular affection after excessive effort

16. PANTOTHENIC ACID, VITAMIN B3 • Source: yeast, eggs, milk, meat, liver, fish, vegetables and intestinal flora • Requirements: 10 g/day • Structure • Metabolism: • absorbed in the intestine by simple diffusion, transported in the blood to the tissues • in the cells, in the cytoplasm, the coenzymes ( 4-P-pantotheine and CoA-SH) are synthesized • the coenzyme is hydrolyzed and the free pantothenic acid (90%) is excreted in urine Pantothenic acid CoA-SH Acetyl-CoA

17. Biochemical functions: Coenzyme • 4-P-pantotheine is coenzyme for acyl-transporting protein of fatty-acid synthetase • Dephospho-CoA is coenzyme for cytrate lyase CoA is involved in: • activation of acetate and fatty acids, oxidation of fatty acids, synthesis of cholesterol and other sterols, synthesis of ketone bodies • Oxidation of pyruvate to 2-oxoglutarate, production of citrate and conversion of succinyl-CoA in Krebs cycle, synthesis of heme using succinyl-CoA • Synthesis of acetyl-choline, acetylglucosamine • Detoxification, production of hyppuric acid • Deficiency: never observed but during scientific experiments • Practical applications: calcium pantothenate, pantotheine, CoA-SH are used in a variety in pharmacological formulations (treating skin and hair diseases and medication of liver, cardiac muscle dystrophy) and perfumery

18. NIACINE, VITAMIN B5, PP • Source: yeast, eggs, milk, meat, liver, fish, vegetables and intestinal flora • Requirements: 10 g/day • Structure: nicotinic acid and nicotinamide • Metabolism: • Alimentary niacin is absorbed in the fundal part of stomach and intestin, mainly by simple diffusion • By blood is supplied to the liver and tissues • Inside the cells, free vitamins exist in small amount; coenzymes are synthesized NAD+ and NADP+; • Coenzymes are brokendown to ADP-ribose and nicotinamide that is excreted in urine NAD+ NADP+

19. Biochemical functions NAD+, NADP+ • Functions of transfer of H in redox reactions • Oxidation of carbohydrates, fatty acids, glycerol, amino acids • Substrate conversion in Krebs cycle • Terminal stages of dehydrogenation in respiratory chain • NADPH+H+ is a hydrogen donor (synthesis of fatty acids, cholesterol, other steroids) • Substrate for synthetic reactions - substrate for DNA-ligase necessary in the replication and repair of DNA • Regulatory function (allosteric effector) controls the activity of citrate synthase, MDH, NAD+-isocitrate DH, etc, controlling the rate of oxidative conversions in Krebs cycle, the rate of gluconeogenesis • Deficiency: PELLAGRA (accompanied by hypovitaminoses of riboflavin and pyridoxamine necessary to synthetize nicotinic acid from tryptophan) Symptoms: skin lesions on exposure to light (photodermatitis), maldigestion, diarrhea, dementia, neuritis, atrophy and painfulness of the tongue (fuchsine-color), hemorrhages of gastrointestinal tract • Practical applications: • Treatment of pellagra, dermatitis, affections of the peripheral nerves, cardiac muscle dystrophy, • Nicotinic acid has vasodilatative action

20. PYRIDOXINE, VITAMIN B6 • Source: • food - cereal, leguminous plants, meat, fish and • intestinal bacteria • Requirements: 2-3 mg/day • Structure: pyridoxine, pyridoxal, pyridoxamine • Metabolism: • absorption in intestine by simple diffusion, • in blood is transported to the tissues • in the cells it is tranformed in coenzymes pyridoxal phosphate (PALP) and pyridoxamine phosphate (PAMP) with the use of flavin coenzymes (B2) PALP PAMP • the breakdown of coenzymes proceeds with dephosphorylation and oxidation • 4-pyridoxic acid is excreted in urine

21. Biochemical functions: coenzyme PALP takes part in nearly all classes of enzymes: oxide-reductases, transferases, hydrolases, lyases, isomerases. The most important reactions are decarboxylation, transamination, racemization of aminoacids, • Deficiency: • Described in children: hyperexcitability of the central nervous system, recurrent convulsions, (insufficient production of GABA, an inhibition mediator for cerebral neurons). • In adults after treatment with isoniazid (tuberculostatic) antagonist of B6: hyperexcitability of the nervous system, polyneuritis, skin lesions • Practical applications: • Treatment of B6 hypovitaminosis, • prophylaxy of isoniazid side-effects, • treatment of polyneuritis, • dermatitis, • gestational toxicosis, • impaired hepatic function, • congenital pyridoxine-dependent anemia

22. FOLACIN, PTEROILGLUTAMIC ACID, VITAMIN B9 • Source - food • vegetable: lettuce, cabbage, spinach, tomato, strawberry, • animal: liver, meat, egg-yolk • Requirements: 400 g/day (800 g/day during pregnancy) • Structure: folacin – folic acid • Metabolism: • Absorbed in small intestine • In the intestinal mucosa tetrahydrofolic acid (THFA) and N5-methyl-THFA are formed • In the blood, 87% are in the erythrocytes and the rest in plasma • Stored in the liver, kidney, intestinal mucosa • Eliminated in urine, feces, sweat

23. Biochemical functions: coenzymes dihydrofolic acid (DHFA), tetrahydrofolic acid (THFA) F FH2 FH4 • take part to the transfer of 1 carbon moiety from one coenzyme to another coenzyme used in the synthesis of • purines, pyrimidines, nucleic acids and cell division • certain aminoacids (glycine from serine, methionine from homocysteine) • Hydroxylation of aromatic aminoacids (phenylalanine, tyrosine, tryptophan) • Deficiency:MEGALOBLASTIC ANEMIA (impaired biosynthesis of nitrogenous bases, DNA and inhibition of mitosis of hemopoietic cells) • Practical applications: treating megaloblastic anemia, stimulation of cell proliferation, during pregnancy

24. COBALAMINS, VITAMIN B12 • Source: food – liver, kidney, intestinal bacteria • Requirement: 2 g/day • Metabolism: • Castle’s factor = intrinsic factor, a glycoprotein produced in the parietal cells of the stomach is needed • Formation of cobalamin-intrinsic factor complex • Binding of the complex to the epithelium of the mucosa of ileum with the participation of Ca2+ • Transport of the complex across the mucosa by endocytosis • Release of the vitamin B12 into the portal vein • In the tissue, mainly in the liver and kidneys, it is converted to coenzymes: methyl-cobalamin (methyl-B12), deoxyadenosylcobalamin (DA-B12) • Mainly excreted in urine

25. Biochemical functions: • Methyl B12 is coenzyme of homocysteine-methyl-transferase in the synthesis of methionine; synergic action with THFA • DA-B12 is coenzyme of methylmalonyl-CoA-mutase essential in the combustion in the Krebs cycle of the propionyl-CoA residues • Facilitate the deposition and production of folic acids coenzymes and involved in the synthesis of DNA and proliferation of hemopoietic cells • Deficiency ADDISON-BIERMER ANEMIA: • Due to the dietary deficit and inadequate absorption because of intrinsic factor deficiency • symptoms of disturbed hemopoiesis, affected posterior and lateral columns of the spinal cord, increased urinary concentration of methyl-malonic acid • Practical application: treatment the megaloblastic anemia, damages of spinal cord and peripheral nerves,

26. ASCORBIC ACID, VITAMIN C • Source: fresh fruits and vegetable (wild-rose fruit) • Requirement: 50-100mg/day • Structure: ascorbic acid dehydroascorbic acid (reduced form) (oxidized form) • Metabolism: • Absorption by simple diffusion in the entire digestive tract, mainly in the intestine • In the blood is partially bound with proteins and in free state • Free ascorbic acid can enter redox reactions • Most ascorbic acid exists in adrenal glands, liver, lungs • Free ascorbic acids and catabolites are excreted in urine

27. Biochemical functions: hydrogen donor in enzymic redox reactions, forming a redox pair with dehydroascorbic acid; the reaction is catalyzed by ascorbate reductase with the participation of glutathione • Serotonine biosynthesis • Hydroxylation of steroids during the synthesis of adrenocortical hormones from cholesterol • Intestinal reduction of Fe3+ to Fe2+, to provide for the iron uptake; release of iron from its binding with the transport protein • Conversion of folic acid to its coenzymes • Hydroxylation of proline and lysine in collagen synthesis • Deficiency SCURVY/SCORBUTUS: • impaired build-up of collagen and chondroitinsulphate of the connective tissue and gradual destruction of the fibrous structure; thus the permeability of the capillaries appears, resulting in subcutaneous hemorrhages • Reduced possibility to use the iron in hemoglobin synthesis and the participation of folic acid in hemopoietic cell proliferation inducing anemia • Loosening and shedding of tooth, hemorrhage of gingivae, dolorous joints, palor of the skin, affected bones, impaired wound healing • Practical applications: treatment of hypovitaminosis (+ folic acid, B12, Fe), stimulating the hemopoiesis, strengthening the walls of capillaries, stimulating regenerative processes, affected connective tissue, respiratory mucosa

28. FAT SOLUBLE VITAMINS General features: • Structure • isopren derivatives • nonpolar structure, hydrofobic, insoluble in water but soluble in organic solvents • Metabolism similar to the lipid metabolism: • To be absorbed in the intestin they need the presence of the bile salts • Transported by chylomicrons to the liver • then stored in liver (ADK) or fat tissue (E) • Functions: important biochemical functions • Vitamin A visual process • Vitamin D metabolism of calcium and phosphorus; considered a pro-hormon • Vitamin E antioxidant role • Vitamin K role in coagulation process

29. FAT-SOLUBLE VITAMINSRETINOLS, VITAMIN A • Source: • All food of animal origin (mainly fish liver, pork, beef liver, egg yolk, milk, sourcream), • vegetal products (carrots, tomato, lettuce) contain carotenoids (provitamins A) • Requirements: 1.5mg/day • Structure: vitamin A1 retinol 1 retinal 1 retinoic acid 1 vitamin A2 retinol 2 (dehydroretinol)

30. Provitamins A = carotenes , , ; the most active, -carotene is oxidized in the intestinal mucosa at the central double bond under the action of carotene dehydrogenase resulting 2 molecules of active retinal that is reduced to retinol -carotene  -carotene + 2 H2O -carotene 2 retinol 1 • Metabolism: • the bile acids are needed for the absorption of vitamin A in the intestin • in the intestinal mucosa retinol forms esters with fatty acids, transported in the chylomicrons • in the plasma retinol is bound with a protein (1-globulin) and transported to the tissues • in the retina, retinol is converted to retinal, a part of rhodopsin (light sensitive protein) and plays an important role in the perception of the visible light. • the retinol esters are stored in the liver; • in the liver it is oxidized to retinal and further to retinoic acid which is excreted in bile as glucuronide

31. Biochemical functions - control of: • Normal growth and cell differentiation (embryo, young organisms) • Division and differentiation of fast proliferating tissues (cartilage, bone, spermatogenetic epithelium, placenta, skin epithelium, mucosa) retinoic acid acts on synthesis of glycoproteins in growing bones and soft tissues) • Photochemical visual act

32. Photochemical visual act: • Rodopsine (the visual pigment) is a conjugated protein formed of a protein opsine and Δ11-cis retinal stereoisomer • When the rodopsine absorbs light 11-cis retinal is transformed in trans retinal producing the nervous stimulation • The complex dissociates in opsin and trans retinal which is reduced by retinal reductase in the presence of NADH+H+ to trans retinol (vit A1) • Light mediates the association of 11-cis retinal with opsin to regenerate rodopsin

33. Deficiency: • Deficiency of dark-adaptation and night blindness • Retardation of growth • Hyperkeratosis of skin follicles, mucosa dryness, xerophtalmia, keratomalacia • Dysordered reproductive function (failure of spermatozoa to fertilize) • Practical application: mixtures of natural vitamin A and synthetic analoques are used to treat hypovitaminoses, visual excessive use, stimulate growth and development of children

34. CALCIFEROLS, VITAMIN D • Source - food of animal origin (liver, butter, milk, yeast), vegetable oils • Requirements: 12-25g/day in child; less for adult • Structure: derivative of steroids, • Vitamin D2 = ergocalciferol is produced from ergosterol = provitamin existing in plants • Vitamin D3 = cholecalciferol is produced in the human skin, from 7-dehydrocholesterol by UV radiation, • Vitamin D4 = dehydroergocalciferol They are biologically inactive 7-dehydrocholesterol cholecalciferol (vitamin D3)

35. Metabolism: • Absorption in the intestin with the help of bile acids • Excreted as chylomicrons transported in the blood to the liver • In the liver: cholecalciferol and ergocalciferol are hydrolyzed by cholecalciferol 25-hydroxylase, in the endoplasmic reticulum, resulting 25-hydroxy cholecalciferol and 25-hydroxy ergocalciferol • They are carried by a calciferol-binding protein to the kidney where, under the action of 1-hydroxylase the 1,25-dihydroxycalciferol is synthesized; this is the active form of vitamin D • Vitamin D is stored in the fat tissue • Eliminated in feces unaltered, oxidized, conjugated 25-hydroxy cholecalciferol1,25-dihydroxycalciferol

36. Biochemical function: control of calcium and phosphate ions transport across the cell membrane acting as a regulator factor for their concentration in the blood: • Transport of calcium and phosphate ions across the epithelium of intestinal mucosa • Mobilization of calcium from the bones • Reabsorption of calcium and phosphate in the renal tubules

37. Deficiency: RICKETS - in children, caused by • the inadequate intake of vitamin D • reduced exposure to UV radiations • low sensitivity of the tissues to calciferols Low concentration of calcium and phosphate in the blood determine impaired bone mineralizatrion, resulting in deformation of the bones of limbs, skull, thorax Relative deficiency is noticed in the patients with chronic diseases of liver and kidney In adults whose growth is complete, the bones are translucid and there is an increased risk for fracture = OSTEOMALACIA • Hypervitaminosis: demineralization of bones with high risk of fracture, calcification of organs (blood vessels, lungs, kidney) • Practical application: prophylaxis and treatment of rickets, osteoporosis, tuberculosis of bones, joints and skin

38. TOCOFEROLS, VITAMIN E • Source: vegetal oil (sun flower, corn, cottonseed, olive, wheat seedling oil) • Requirements: 20-50 mg/day • Structure: There are -, -, -, -tocopherols depending on R -tocopherol

39. Metabolism: • Absorption needs the presence of fats and bile acids as emulsifying agents • In intestine absorbed by simple diffusion • Transport as chylomicrons through lymph and blood, complexed with lipoproteins, to organs and tissues where it is concentrated in membranes • Most of it is stored in adipose tissue, liver, skeletal muscles • Eliminated in feces; metabolites eliminated in urine

40. Biochemical functions: • A biological antioxidant that provides the stability of cell membranes. Controls the rate of free-radicals reactions in the living cells by inhibiting spontaneous chain reactions of peroxide oxidation of unsaturated lipids in biomembranes • Increases the biological activity of vitamin A by protecting its unsaturated side chains from peroxide oxidation • Deficiency: in premature infants leading to hemolytic anemia • Practical application: • Antioxidant to prevent excessive lipid peroxide accumulation • Prophylaxis of sterility and abortion, liver diseases, muscular atrophy, congenital diseases of erythrocyte membrane

41. NAPHTOQUINONE, VITAMIN K • Source: green vegetables, liver, intestinal bacteria • Requirements: 2 mg/day • Structure: quinones with an isoprene side chain; various forms that differ in the length and degree of unsaturation of the long side chain; there are • phylloquinones (vitamins K1) in plants and • menaquinones (vitamins K2,, MQ) synthesized by intestinal bacteria or derived from naphtoquinones metabolism in the tissues

42. Metabolism: • Bile acids and pancreatic lipase are needed for the intestinal absorption • Transported with the chylomicrons; in the blood plasma it is bound with albumins to be stored in the liver, spleen, heart • In the tissues they are transformed to MQ-4 that serves as biologically active form of vitamin K • The end products of catabolism are excreted in the urine

43. Biochemical functions: • control of the blood coagulation – participate to the build-up of • factor II (prothrombin), • factor VII (proconvertin), • factor IX (Christmas), • factor X (Stewart); • conversion of pro-prothrombin to prothrombin in the liver, triggers fibrin clot formation. • Deficiency • Predisposition to hemorrhagic disease • In adults the intestinal flora provides a complete supply; in children the alimentary deficit is described • Causes: • suppression of intestinal flora by drugs • disease of gallbladder with reduced production of bile acids, needed for absorption; • disease of liver involved in the activation of vitamin K and synthesis of coagulation factors. • Practical application: treatment of hemorrhagic diseases

44. VITAMIN F, ESSENTIAL FATTY ACIDS • Source: exclusively vegetal • Structure: polyunsaturated fatty acids • Functions: • components of the phospholipids and other structural lipids of the cell and intracellular membranes • growth and normal development of the organism • normal ovulation • prevent the dermatitis and dryness of skin • precursors of prostaglandins • Deficiency: • lack of vitality in newborn, stop of growth, • reduced reproductive capacity • fragile capilaries