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2016.02.26. Nutrition - vitamins 22.02.2016. Energy „flow” in the organism Daily energy expenditure ~ 10.000 KJ (2500 kCal) PHYSICAL WORK NUTRIENTS HEAT PRODUCTION BREAKDOWN (CATABOLISM) WASTE PRODUCTS ATP SYNTHESIS (ANABOLISM) BODY COMPOSITION STORAGE SUBSTANCES 1 2016.02.26. Energy and substrate „flow” in the organism Total caloric intake ~ 10.000 KJ (2500 kCal) PHYSICAL WORK NUTRIENTS HEAT PRODUCTION BREAKDOWN WASTE PRODUCTS SYNTHESIS ATP (CATABOLISM) (ANABOLISM) BODY COMPOSITION STORAGE SUBSTANCES Nutrients Macronutrients: Carbohydrates 17,2 kJ/g Proteins Fats 17,2 kJ/g 38,9 kJ/g Utilization of the metabolic energy: Isodynamic law: for energy purposes different nutrients may replace one another in accordance with their caloric (energy) values Max Rubner – (1923) Supply of precursor molecules for synthetic processes: The isodynamic law is not fully applicable because of the need of essential food constituents, which has to be taken up by the food (e.g. essential amino/fatty acids) 2 2016.02.26. Polar expeditions PEMMICAN – protein and fat rich food, originally produced by polar eskimo tribes 100g ~1600 KJ Traditionally, pemmican was prepared from the lean meat of large game such as buffalo, elk or deer. The meat was cut in thin slices and dried over a slow fire, or in the hot sun until it was hard and brittle. Then it was pounded into very small pieces, almost powder-like in consistency, using stones. The pounded meat was mixed with melted fat with a ratio of approximately 50% pounded meat and 50% melted fat. In some cases, dried fruits such as saskatoon berries, cranberries, blueberries, or choke cherries were pounded into powder and then added (www.wikipedia.de) to the meat/fat mixture. Other food constituents (including micronutrients) Vitamins: vitamins are not energy sources but are essential cofactors in many metabolic processes. They are not synthetised (or not in sufficient amount) in the human body. Water Minerals: Na+, K+, Ca2+, Mg2+, Cl-, HPO42- Trace elements: elements which are needed in minute quantities for the proper growth, development, and physiology of the organism. iron, iodide, fluoride, copper, managanese, selenium, zinc, chromium, molibdenium, etc. Spices: smell and taste substances – GIT reflexes (secretion, motility) Fibres: non-digestable portion of the food (volume – GIT motility) Additives, breakdown products, etc. 3 2016.02.26. Carbohydrates Mono- and disaccharides Glucose (neurons, erythrocytes – glu-dependent cells) Sucrose (refined carbohydrates: sweets, soft drinks) Lactose: milk (human and cow), diary products (lactose intolernce) Fructose: fruits, juices Oligosaccharides Dextrin: e.g.: toast, biscuits Polysaccharides Plant origin: starch – cereals, potato, corn, rice, beans this is the major source of energy in normal nutrition! cellulose fibers Animal origin: glycogene Proteins To keep a nitrogen balance of the body: ~30 g/day WHO recommendation: 0.8-1g/kg b.w. Essential amino acids (there is no de novo synthesis in the human body) Lys, Trp, Phe, Met, Tre, Leu, Ile, Val Biological value (BV) of proteins: measure of the proportion of absorbed protein from a food which becomes incorporated into the proteins of the organism's body. Proteins of animal origin – high BV (they contain all of the essential amino acids, with a nearly optimal composition) meat (75%), milk, diary products (lactalbumin, lactoglobulin, casein; ~85%), egg (ovalbumin; 94%), whey protein (~100%!) Proteins of plant origin: usually lower BV whole wheat (gliadin, glutein; 52%), beans (soybean; 73%) But e.g.: corn (zein)– low tryptophan content 4 2016.02.26. Nitrogen balance of the body http://www.ucl.ac.uk/~ucbcdab/Nbalance/Nbalance.htm Explanation of the concept of the biological values of proteins Type 1. food protein Proteins of the body BV = 100% Type 2. food protein BV=50% 5 2016.02.26. B.V. (Biological Value) is the proportion of absorbed protein that is retained in the body for maintenance and/or growth. The highest score of 100 was given for the best protein at the time, egg. However, whey protein came along and proved even better than egg. P.E.R. (Protein Efficiency Ratio) is the gain in body weight divided by the weight of the protein consumed. N.P.U. (Net Protein Utilization) is the proportion of protein intake that is retained (calculated as BV times Digestibility). PDCAAS (Protein Digestibility Corrected Amino Acid Score) is based on the amino acid requirements of humans. A protein scoring a 1.0 indicates it meets all the essential amino acid requirements of humans according to the Food Agriculture Organization and World Health Organization Fat High energy content Major sources are triglycerides (glycerol + fatty acids) Fatty acids – saturated FAs - unsaturated FAs– polyunsaturated fatty acids (PUFA): essential FA!! Cholesterol and cholesterol derivates Lipid soluble vitamins (A,D,E,K) Fats of animal origin: Lard, bacon, butter, etc.; +hidden fat (muscle) Fats and oils of plant origin: These are rich in essential fatty acids (PUFA – linolenic acid, arachidonic acid, etc.) Oily seeds (sunflower, rasp, peanut, olive) Hardening: saturation of the unsaturated FA with hydrogenation : tarns -UFAs 6 2016.02.26. Correlation between the serum cholesterol level and the incidence of heart disease Optimal: < 5.2 mmol/l Framingham Heart Study – 1949 - 7 2016.02.26. LDL – cholesterol -- atherosclerosis 8 2016.02.26. Rules for the optimal daily food intake 1. The energy content of the food should cover the energy expenditure 2. Should contain the minimal daily requirements of proteins, carbohydrates and fats 3. Should also contain the minimal RDAs of vitamins, minerals and trace elements 4. Toxic components should be lower than the upper tolerable limit Optimal relative proportions of macronutrients to cover daily energy requirements proteins (ca.: 1 g/kg b.w.) Pro: nitrogen balance Con: calorigenic effect digestibility carbohydrates (min. 10%) Pro: antiketogenic Con: „empty” calory 15% 25% fats (1/3 essential FA) Pro: essential FA, ADEK vits. Con: „empty” calory hypercholesteraemia ketogenic effect 60% Trace elements Iron:(12-18 mg/d) – meat, egg, vegetables (spinach, broccoli) Iodide: (180 - 200 µg/d) – tap water, salt hypothyroidism, goiter geographical differences: endemic goiter Fluoride:(1 mg/d) – tap water supplementation, toothpaste, pills: + Selenium Zinc Manganese Molybdenum etc. 9 2016.02.26. http://what-when-how.com/molecular-biology/metal-requiringenzymes-molecular-biology/ Food piramyde Fats, Oils & Sweets Use Sparingly Milk, Yogurt, & Cheese Group 2-3 Servings Vegetable Group 3-5 Servings Meat, Poultry, Fish, Dry Beans, Eggs, & Nuts Group 2-3 Servings Fruit Group 2-4 Servings Bread,Cereal, Rice, & Pasta Group 6-11 Servings 10 2016.02.26. http://health.gov/dietaryguidelines/2015/guidelines/ 11 2016.02.26. 12 2016.02.26. Determination of the ideal body mass BMI= Body Mass Index (Quetelet index): body weight (kg)/(body high in meter)2 normal range: 19-25 The ideal body composition (% of the body weight): extra cellular fluid volume: 15% total fat content 20% total muscle content 40% 13 2016.02.26. Determination of the „Lean Body Mass” value – total fat mass Thickness of the skin fold (subcutaneous fat layer) Age (years) Women Men 14 2016.02.26. Historical background – vitamin research Sir Frederick Gowland Hopkins: 1861-1947 (Nobel prize 1929) „Hopkins suspected that minute amounts of unknown, chemicals were necessary in the diet. He fed mice solely on fat, starch, salts, and purified milk protein (containing all the essential amino acids). They became sick and ceased to grow. However, when also given a very small quantity of whole milk, they recovered. This led to the isolation of types vitamin „B”, and what Hopkins called "fat-soluble A" (actually two vitamins: A and D).” Christian Eijkmann and the discovery of the importance of nutrition and the pathogenesis of Beriberi (Nobel prize 1929) Beriberi disease – peripheral neuropathy, pain, palsy, muscle atrophy, cardivascular complications 15 2016.02.26. http://www.nobelprize.org/ 16 2016.02.26. Vitamins: vitamins are not energy sources but are essential cofactors in many metabolic processes. They are not synthesized (or not in sufficient amount) in the human body. origin: “Vital amine” - „Vitamine” (Casimier Funk, 1912) 1913 E.V. McCollum: alphabetical nomenclature (A, B, C, D) 1920: Jack Cecil Druommond: „Vitamin” (not all vitamins are „amines”) •Vital compounds – (long term) deprivation results in symptoms and illnes •exogenous -”essential” substances (exemptions: vit. D, B3) •Daily uptake is low (micrograms - 100 mg/d) •Energy content is not significant – biological function! Diverse functions of vitamins • Constituent of enzymes or enzyme complexes (prostetic groups, co-enzymes) • Non-enzymatic protein complexes (retinol – rhodopsin) • antioxidants: neutralization of reactive oxygen radicals (vit. A, E, C) • Signalization: hormone - activated vitamin D 17 2016.02.26. year Discovery of vitamins and their chemical structures vitamin 1909 Vitamin A retinol 1912 Vitamin B1 thiamine 1912 Vitamin C ascorbic acid 1918 Vitamin D calciferol 1920 Vitamin B2 riboflavin 1922 Vitamin E tocopherol 1926 Vitamin B12 cobalamine 1929 Vitamin K phyllochinon 1931 Vitamin B5 pantothenic acid 1931 Vitamin B7 biotin 1934 Vitamin B6 pyridoxin 1936 Vitamin B3 niacin 1941 Vitamin B9 folic acid Nobel Prize in Phsiology and Medicine Discovery of Vitamins Christiaan Eijkman (1929) Vitamin B1 Sir Frederick Gowland Hopkins (1929) Growth Stimulating Vitamins George Hoyt Whipple (1934)* Vitamin B12 George Richards Minot (1934)* Vitamin B12 William Parry Murphy (1934)* Vitamin B12 Henrik Carl Peter Dam (1943) Vitamin K Isolation of Vitamins Adolf Otto Reinhold Windaus (1928)* Vitamin D Albert von Szent-Györgyi Nagyrapolt (1937) Vitamin C Richard Kuhn (1938) Vitamin B2 and B6 Edward Adelbert Doisy (1943) Vitamin K Nobel Prize in Chemistry Synthesis of Vitamins Walter Norman Haworth (1937) Paul Karrer (1937) Robert Burns Woodward (1965)* Vitamin C Vitamin E Vitamin B12 Structure of Vitamins Paul Karrer (1937) Richard Kuhn (1938) Lord (Alexander R.) Todd (1957)* Dorothy Crowfoot Hodgkin (1964)* Vitamin A and E Vitamin B2 Vitamin B12 Vitamin B12 18 2016.02.26. The Nobel Prize in Chemistry 2004 was awarded jointly to Aaron Ciechanover, Avram Hershko and Irwin Rose "for the discovery of ubiquitin-mediated protein degradation". MTA (HAS) Inaguration lecture, 2005.(www.videotorium.hu) Provitamins Precursors of vitamins which will be converted into biologically active compounds by the cells of the organism Examples: ß-carotin – retinol (vit. A) D - vitamin: cholesterol – dehydrocholesterol –cholecalciferol (D3) ergocalciferol (D2, plant origin) Hydroxylation: (liver, kidney) - 1,25-dOH-cholecalciferol (active) 19 2016.02.26. Antivitamins Compounds having selective antagonistic effects with the biological actions of vitamins examples: vit. K – coumarin derivatives (anticoagulants): warfarin avidin (egg white) – high affinity binding of biotin (vit. B7) methotrexat (cytostaticum) – antagonist of folic acid (vit. B9) – (reduction of the activity of dihydrofolate-reductase) antidote: supplementation of the corresponding vitamin! Methotrexat Folic acid 20 2016.02.26. RDA – Recommended Daily Allowance RDA is usually within the mg/d range exempitons: B12, D: microgram/d range vit. C .: 75-100 mg/d IE (IU) – International Unit: vitamin activity is conferred by a mixture of biologically active substances Fig. 1. The risks of adverse health effects from decreasing intakes and the risks of adverse health effects with increasing intakes. The Estimated Average Requirement (EAR) reflects the intake where 50% of a population group is at risk of inadequacy, whereas the Tolerable Upper Intake Level (UL) is set an uncertainty factor lower than the No Observed Adverse Effect Level (NOAEL) or Lowest Observed Adverse Effect Level (LOAEL). The Recommended Nutrient Intake (RNI) is set at two standard deviations above the EAR and reflects the intake level at which 2.5% of a population group is at risk of inadequacy. 21 2016.02.26. Hypo- or avitaminosis Avitaminosis is any disease caused by chronic or longterm vitamin deficiency • RDA is dependent on: age, gender, body weight, physical activity, stressors, pregnancy, lactation, etc. • General symptoms: restricted physical and mental performance • Sensitive tissues and organs: high metabolic (myocardium, nervous system, immune system) or mitotic activity (skin, mucous membrane epithel cells, bone marrow) Causes of avitaminosis • • • • Decreased intake Malabsorption Increased demand Special conditions: climatic conditions (UV-irradiation, insolation) damage of the colonic bacterial flora lack of prophylaxis 22 2016.02.26. Vitamin and trace element supply in the female population of Germany Hypervitaminosis No-Observed-Adverse-Effect Level (NOAEL) Lowest-Observed-Adverse-Effect Level (LOAEL) Tolerable Upper Intake Level (UL) 23 2016.02.26. Estimated Average Requirements Recommended Daily Allowance Tolerable Upper Intake Level 24 2016.02.26. Name Synonym Chemical name Vitamin A Axerophtol, Retinol Retinol Vitamin B1 Aneurin Thiamine Vitamin B2 Lactoflavin, Vitamin G Riboflavin Vitamin B3 Vitamin PP, Vitamin B5 Niacin Vitamin B5 Vitamin B3 Pantothenic acid Vitamin B6 Adermin, Pyridoxol Pyridoxin, Pyridoxal and Pyridoxamin Vitamin B7 Vitamin H, I vagy Vitamin Bw Biotin Vitamin B9 Vitamin M vagy Vitamin Bc Folic acid Vitamin B12 Erythrotin Cobalamin Vitamin C Ascorbic acid Vitamin D Calciferol Vitamin E Tocopherol Vitamin K Phyllochinon and Menachinon Classification of vitamins 1/ lipid soluble vitamins: A, D, E, K, (F) •Absorption together with other lipids •Accumulation and storage in the adipose tissue (large reserves, except: K) •Blood transport - lipoproteins •Excretion: bile (liver) 2/ Water soluble vitamins: B-group and vit. C •Specific (carrier mediated) absorption in the gut •Restricted reserves (few weeks) – except: B12 - liver •Excretion: kidney 25 2016.02.26. A Retinal pigment Coenzyme in B1 (thiamine) decarboxylation of pyruvate and α-keto acids Male: 1000 µg Female: 800 µg Follicular hyperkeratosis, night blindness Male: 1.5 mg Female: 1.1 mg Beriberi B2 (riboflavin) Coenzymes FAD and FMN, H carriers in mitochondria Male: 1.7 mg Female: 1.3 mg Hyperemia of nasopharyngeal mucosa, normocytic anemia B3 niacin (nicotinic acid) Coenzymes NAD and NADP, H carriers in mitochondria Male: 19 mg Female: 15 mg Pellagra B6 (pyridoxine) Coenzyme in transmination for synthesis of amino acids Male: 2 mg Female: 1.6 mg Stomatitis, glossitis, normocytic anemia B12 (cobalamin) Coenzyme in reduction of ribonucleotides to deoxyribonucleotides. Promotes formation of erythrocytes, myelin 2 µg Pernicious anemia (a megaloblastic anemia) C (ascorbic acid) Coenzyme in formation of hydroxyproline used in collagen 60 mg Scurvy D (1,25-cholecalciferol) Ca2+ absorption 5-10 µg Rickets, osteomalatia E (α-tocopherol) Antioxidant: thought to prevent oxidation of unsaturated fatty acids Male: 10 mg Female: 8 mg Peripheral neuropathy K (K1 = phylloquinone, K2 = various menaquinones) Male: 70-80 µg Clotting: necessary for synthesis by liver of prothrombin and factors VII, IX Female: 60-65 and X µg Hemorrhagic disease Folate (B9) Backbone used to synthesize purines and thymine Male: 200 µg Female: 180 µg Pregnancy: 400 µg Megaloblastic anemia Biotin (B7) Coenzyme in carboxylation reactions 30-100 µg* Neurologic changes Pantothenic acid (B5) Coenzyme A (CoA). Necessary for carbohydrate and fat metabolism involving acetyl-CoA; amino acid synthesis 4-7 mg* Abdominal pain, vomiting, neurologic signs 26 2016.02.26. Albert von Szent-Györgyi Nagyrápolt Nobel Prize - 1937 "for his discoveries in connection with the biological combustion processes, with special reference to vitamin C and the catalysis of fumaric acid" „So the reaction 2H + O = H2O, which seems such a simple one, breaks down into a long series of separate reactions. With each new step, with each transfer between substances, the hydrogen loses some of its energy, finally combining with oxygen in its lowest-energy compound. So each hydrogen atom is gradually oxidized in a long series of reactions, and its energy released in stages.” Nobel lecture: Szent-Györgyi – Krebs – „Half-cycle” 27 2016.02.26. Vitamin C (ascorbic acid) Defic.: scurvy, Möller-Barlow disease Bleedings (blood vessels) , aortic aneurism immundeficiency Biological action: proline and lysine hydroxilation synthesis of collagene Dopamine hydroxilation (synthesis of cathecolamines)- depression (?) GIT absorption of iron ions antioxidant RDA: 70-100 mg/d (vegetables, fruits) 28 2016.02.26. In humans, primates and guinea pigs the enzyme gulonolacton-oxidase is missing Genetically – there is no endogenous synthesis of Vit. C 29 2016.02.26. Vitamin A (Axerophthol, Retinol) RDA: 1,5 mg/d (5000 IE) (liver, eggs, diary products, oily seeds) ß-carotin: vegetables retinol (retinal) – photo pigments (rod- and photopsins) retinoid receptors – auto- and paracrine effects protection of the epidermis and mucosal epithelial cells Deficiency: •Xerophtalmus, keratomalacia (destruction of the cornea) •Hemeralopy (decreased dark adaptation, „night blindness”) •Impaired growth •Dysfunction of the epithels of the mucous membranes (mucin – ceratin) •Antioxidant and scavenger function Hypervitaminosis (dermatitis, hair loss, increased ICP) Terratogeneic effect – disturbance of the intrauterine development 30 2016.02.26. Keratomalacia Vitamin D (anti-rachitis (rickets) vitamin) RDA: 12 µg/d (500 IE) (fish oil, diary products, oily seeds) D2 (ergocalciferol) - plant origin D3 (cholecalciferol) - animal origin Active forms: 1,25 dihydroxi-cholecalciferol (kidney, liver) Biological action: GIT transepithelial transport of Ca2+ (regulation of the expression of Calbindin, Ca++ pumps) Defic.: rachitis, osteomalacia D-hypervitaminosis (hypercalcemia) 31 2016.02.26. 32 2016.02.26. 33 2016.02.26. 34 2016.02.26. Vitamin E (alpha - tocopherol) RDA: 10 mg/d (green vegetables, oily seeds) Antioxidant – inactivates of the reaktive oxygene radicals Deficiency: •Human: less understood - peripheral neuropathy? •Animal models: sterility, spontaneous abortion Vitamin K (phylloquinone, menaquinone) RDA: 10 µg/d vegetables, importance of the gut flora („microbiome”) Deficiency: bleedings, impaired bone development (Antivitamins: coumarine derivates) Biological effects: Vitamin-K dependents coagulation factors II. VII. IX. X., protein S and C Bone formation: – osteokalcin (Gla-protein) 35 2016.02.26. Free radical mechanism of lipid peroxidation coumarin coumarin 36 2016.02.26. A Retinal pigment Coenzyme in B1 (thiamine) decarboxylation of pyruvate and α-keto acids Male: 1000 µg Female: 800 µg Follicular hyperkeratosis, night blindness Male: 1.5 mg Female: 1.1 mg Beriberi B2 (riboflavin) Coenzymes FAD and FMN, H carriers in mitochondria Male: 1.7 mg Female: 1.3 mg Hyperemia of nasopharyngeal mucosa, normocytic anemia B3 niacin (nicotinic acid) Coenzymes NAD and NADP, H carriers in mitochondria Male: 19 mg Female: 15 mg Pellagra B6 (pyridoxine) Coenzyme in transmination for synthesis of amino acids Male: 2 mg Female: 1.6 mg Stomatitis, glossitis, normocytic anemia B12 (cobalamin) Coenzyme in reduction of ribonucleotides to deoxyribonucleotides. Promotes formation of erythrocytes, myelin 2 µg Pernicious anemia (a megaloblastic anemia) C (ascorbic acid) Coenzyme in formation of hydroxyproline used in collagen 60 mg Scurvy D (1,25-cholecalciferol) Ca2+ absorption 5-10 µg Rickets E (α-tocopherol) Antioxidant: thought to prevent oxidation of unsaturated fatty acids Male: 10 mg Female: 8 mg Peripheral neuropathy K (K1 = phylloquinone, K2 = various menaquinones) Clotting: necessary for synthesis by Male: 70-80 µg liver of prothrombin and factors VII, IX Female: 60-65 and X µg Hemorrhagic disease Folate (B9) Backbone used to synthesize purines and thymine Male: 200 µg Female: 180 µg Pregnancy: 400 µg Megaloblastic anemia Biotin (B7) Coenzyme in carboxylation reactions 30-100 µg* Neurologic changes Pantothenic acid (B5) Coenzyme A (CoA). Necessary for carbohydrate and fat metabolism involving acetyl-CoA; amino acid synthesis 4-7 mg* Abdominal pain, vomiting, neurologic signs 37 2016.02.26. 38 2016.02.26. (Vitamin F) Legalább 3.5 %-a az teljes energiabevitelnek Többszörösen telítetlen zsírsavak (Poly Unsaturated Fatty Acid; PUFA): linolsav, linolénsav (esszenciális zsírsavak) hatása: Foszfolipid és prosztaglandin szintézis 39 2016.02.26. Vitamin B1 (thiamin, aneurin) 10mg/nap előfordulás: húsfélék, teljesőrlésű lisztfélék termolabilis piruvát-dehydrogenáz komplex koenzime – dekarboxyláció hiánybetegség: beri beri (ld. hántolatlan rizs) Polyneuritis, kardiális tünetek, KIR tünetek 40 2016.02.26. Vitamin B2 (riboflavin) 1.5 mg/d előfordulás: tej, hús, tojás, halhús Termostabil flavin mononukleotid Flavin Adenine Dinucleotid (FAD), Flavin-Mononucleotid Proton-elektron transzportfolyamatok koenzime hiánytünet: száj (nyelv) nyálkahártya gyulladása, fejfájás 41 2016.02.26. Niacin, nikotinsav, B3 dehidrogenázok koenzime (NADH) redox folyamatok koenzime 15-30 mg/d Hiány csak akkor alakul ki, ha a triptofán bevitel is korlátozott pelle agra (durva bőr, dermatitis), fekete nyelv (glossitis) 3D: Dermatitis, Diarhea (hasmenés)‚ Dementia, (Death) Előfordul: tej, mogyoró, élesztő 42 2016.02.26. Vitamin B6 (pyridoxal, pyridoxamin, pyridoxol) koenzim – amino-transzferázok Hiány: emberben nagyon ritka dermatitis, görcsök, émelygés, hányás előfordulás: hús, máj, élesztő, mogyoró 2.0-2.2 mg/d 43 2016.02.26. Pantoténsav (B5): CoA- koenzim része hiány: őszülés, memória zavarok Védi a bőrt 10-15 mg előfordulás: általános pantotensav Biotin (H vagy B7 vitamin) koenzim (biotinil-lizil enzim) karboxylázok (piruvát dekarboxiláz) hiánybetegség: dermatitis, neuromuszkuláris zavarok (izomgyengeség) (nyers tojás fogyasztása: Avidin!) Napi bevitel: 100 µg Előfordul: máj, vese, élesztő 44 2016.02.26. B12 vitamin (cyanocobalamin, antipernicioza vitamin) hiány: anaemia perniciosa, funikuláris myelosis (hátsókötegi rsz.) •vérképzés – nukleotid (purine), szintézis (DNA), C1 csoportok szállítása threonin, valin, isoleucin, methionin anyagcsere előfordulás: húsfélék, máj Napi bevitel: 3 µg – (nagy raktárak a májban) Folsav (B9 vitamin) (tetrahydrofolsav, FH4) C-1 csoportok transzportja (nukleutid, aminosav anyagcsere) hiány: anaemia perniciosa (mint B12 hiány esetén) Terhesség alatt: csökkenti a velőcső záródási zavarok gyakoriságát Napi bevitel: 0.3 mg Előfordulás: máj, növényi levelek (saláta, spenót, brokkoli, stb.) Antivitamin: Methotrexat (citosztatikum) Szulfonamidok: para-amino benzoesav analóg - antibakteriális hatásúak 45 2016.02.26. http://www.ucl.ac.uk/~ucbcdab/Nbalance/N balance.htm 46