The B Vitamins--As Individuals

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Chloe Ross
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1 B Vitamins

2 The B Vitamins--As Individuals The B vitamins are very active in the body. Several of the B vitamins form part of the coenzymes that assist enzymes in the release of energy. Other B vitamins participate in metabolism and cell multiplication. Recommendations for the B vitamins come from RDA, AI, and Tolerable Upper Intake Levels. There are deficiencies, toxicities and food sources that are unique for each vitamin.

5 Thiamin (vitamin B1) Antiberiberi or antinatriuretic vitamin. Essential for carbohydrate utilization. Specific coenzyme form is thiamine pyrophosphate (TPP) TPP is intimately connected with energy releasing reaction in carbohydrate metabolism.

6 Sources & RDA Occurs mostly in all natural foods. Important sources are: whole and enriched grains, cereals, wheat, yeast, pulses, legumes, oilseeds & groundnut, meats (pork), milk, and eggs. Milk is important source for infants. RDA (adults): From 1.2 to 1.5 mg daily intake is recommended The RDA, which is higher with a diet high in refined carbohydrates, decreases slightly with age.

7 2001 Brooks/Cole, a division of Thomson Learning, Inc. Thomson Learning is a trademark used herein under license. Thiamin Pork is the richest source of thiamin, but enriched or whole-grain products typically make the greatest contribution to a day s intake because of the quantities eaten.

9 Functions of Thiamin (vitamin B1) Thiamin pyrophosphate (TPP) is required for proper nerve transmission. TPP is the coenzyme for several key enzymes. a. Pyruvate and the alpha -ketoglutarate dehydrogenases (glycolysis and the citric acid cycle) b. Transketolase (the pentose phosphate pathway) c. Branched-chain keto-acid dehydrogenase (valine, leucine, and isoleucine metabolism)

10 Thiamin (TPP) - Vit B1 - involved in the conversion of pyruvate to acetyl-coa - deficiency results in a condition known as beriberi - damage to nervous system, brain function, heart and muscles.

11 Thiamine deficiency is seen Classically - in people subsisting on polished rice, alcoholics, cancer victims who do not eat, women with extreme vomiting of pregnancy, children and adults who have been starved.

12 Deficiency leads to beriberi Biochemically - Carbohydrate metabolism is impaired so that pyruvate accumulates in the tissue. Plasma pyruvate concentration rises and it is also excreted in urine. There is also accumulation of lactic acid in body fluids. Accumulation of pyruvate in the brain is responsible for the polyneuritis seen in beriberi. Clinically - impairment of the cardiovascular, nervous, and gastrointestinal systems.

13 Beriberi occurs in three stages: a. Early: loss of appetite, constipation and nausea, peripheral neuropathy, irritability, and fatigue b. Moderately severe: WernickeKorsakoff syndrome (seen in chronic alcoholics), which includes mental confusion, ataxia (unsteady gait, poor coordination), and ophthalmoplegia (loss of eye coordination)

14 Wernicke-Korsakoff syndrome Wernicke s Encephalopathy Most common CNS-related neurological problem in alcoholics. Seen in chronic alcoholics as body demand for thiamine is increased in them. Characterised by loss of memory, rhythmical to & fro motion of the eyeball. Wernicke syndrome responds dramatically to thiamine administration. Thiamine has also been successfully used to treat depression.

15 Wernicke syndrome Gait disturbance- ataxia of gait Nystagmus - weakness of eye movement Ophthalmoplegia Mental disturbance Korsakoff syndrome is a more advanced stage than Wernicke syndrome Short term memory loss Compensatory confabulation

16 C. Severe (1) Dry beriberi includes all of the signs and symptoms in a and b plus more advanced neurologic symptoms, with atrophy and weakness of the muscles (e.g., foot drop, wrist drop). Dry beriberi is characterised by neurological disorders - peripheral neuritis. (2) Wet beriberi includes the symptoms of dry beriberi in combination with generalized edema (as shown in the next slide) acute high-output cardiac failure, and pulmonary congestion. The dilated cardiomyopathy of wet beriberi responds promptly to thiamine administration. (3) Infantile form

18 Infantile beriberi Infants under 6 months of age receiving inadequate thiamine in milk. In acute form, - dyspnea and cyanosis death from cardiac failure. Aphonia may be present and the infant may appear to be crying without emitting much sound. Diarrhea, wasting, vomiting and edema may be present There is NO known toxicity for this vitamin.

19 THIAMINE PYROPHOSPHATE Oxidative decarboxylation of α-keto acids Transketolase reaction

Severe neurological symptoms Ataxia Mental confusion Loss of eye coordination

20 THIAMINE PYROPHOSPHATE DEFICIENCY (BERIBERI) EARLIEST SYMPTOMS Constipation Appetite suppression Nausea Mental depression Peripheral neuropathy Fatigue CHRONIC DEFICIENCY Severe neurological symptoms Ataxia Mental confusion Loss of eye coordination Cardiomegaly Cardiac failure Musculature defects WERNICKE-KORSAKOFF SYNDROME Amnesia Encephalopathy

21 Riboflavin (Vit B2) Riboflavin Coenzymes: Flavin mononucleotide (FMN) and Flavin adenine dinucleotide (FAD) Play important role in maintaining integrity of mucocutaneous structure. Have a fundamental role in cellular oxidation.

22 Sources & RDA Rich food sources include liver, kidney, meat, eggs, green leafy vegetables, milk, enriched and whole grain breads and cereals. Richest natural source are milk, egg,, & green leafy vegetables Meat & fish contain small amounts. RDA (adults): 1.1 to 1.3 mg The allowance recommended for adults is 0.6 mg /per 1000 kcal and not less than 1 mg per day to maintain tissue saturation mg/day for adults & higher intakes for pregnancy & lactation.

24 Function. Riboflavin is converted to the oxidation reduction coenzymes flavin aclenine dinucleotide (FAD) and flavin adenine mononucleotide (FMN).

25 Deficiency signs and symptoms Deficiency - usually deficiency of B-complex. Ocular symptoms- eye strain and fatigue, itching, burning, and sensitivity to light may precede other symptoms. Angular stomatitis and cheilosis/ cheilitis (inflammation and cracking at the corners of the mouth or at the corners of the lips.) Glossitis, or a red and swollen tongue Scaly dermatitis, particularly at the nasolabial folds and around the scrotum Localized seborrheic dermatitis of the face, hands (glove dermatitis) Behavioral changes have been reported There is NO known toxicity for this vitamin.

27 B2 - FLAVIN NUCLEOTIDES They are derivatives of riboflavin or vitamin B2 Riboflavin (B2) Riboflavin (B2) Flavin Mononucleotide (FMN) Flavin Adenine Dinucleotide (FAD)

28 FMN - FLAVIN MONONUCLEOTIDE FMN Riboflavin Dehydrogenation of two consecutive carbon atoms Dehydrogenation of NAD+ in Electron Transport Chain Riboflavin (B2) FMN

29 FAD - FLAVIN ADENINE DINUCLEOTIDE FAD Riboflavin Dehydrogenation of two consecutive carbon atoms Riboflavin (B2) FMN FAD Ariboflavinosis

adequate amounts of the vitamin in the diet. Riboflavin decomposes when exposed to visible light.

31 B2 - ARIBOFLAVINOSIS Glossitis Seborrhea Angular stomatitis Cheilosis Photophobia It is often seen in chronic alcoholics It is rare in USA and other developed countries due to the presence of adequate amounts of the vitamin in the diet. Riboflavin decomposes when exposed to visible light. This characteristic can lead to a deficiency in newborns treated for hyperbilirubinemia by phototherapy.

32 Vitamin B6 (pyridoxine, pyridoxamine, and pyridoxal) The term Vitamin B6 is used to collectively represent 3 compounds namelyi) Pyridoxine ii) Pyridoxal iii) Pyridoxamine

33 Sources & RDA Vitamin B-6 is widespread in nature. Rich sources include yeast, whole grain cereals, whole wheat, legumes, nuts and seeds, vegetables, liver, lean meat, fish, corn, egg yolk, and milk. RDA (adults): 1.3 to 1.7 mg Recommended daily requirement for adults is about 2-2.2mg per day. Pregnancy,lactation & old age: 2.5mg/day. The drugs isoniazid and penicillamine increase the requirement for vitamin B6. Toxicity in humans has been described when taken at extremely high doses.

34 Function of Vitamin B6 (pyridoxine, pyridoxamine, and pyridoxal) Pyridoxal phosphate and pyridoxamine phosphate are coenzymes Pyridoxal phosphate is the coenzyme involved in transamination and other reactions of amino acid metabolism. Biochemical functions promoted is amino-group transfer. synthesis and catabolism of amino acids, synthesis of neurotransmitters, porphyrins and niacin. PLP enzyme catalyzes transaminations, decarboxylations, deaminations, racemizations and aldol cleavages and condensations, transsulfuration.

35 Clinical usefulness. High doses of vitamin B6 are used to treat homocystinuria resulting from defective cystathionine ~3-synthase. Prolonged high intake (> 500 mg/day) (except as in 5.) may lead to vitamin B6 toxicity with sensory neuropathy.

36 Deficiency is manifested by 3 different types of symptoms. neuropathic: due to insufficient neurotransmitter synthesis. anemic: due to low porphyrin synthesis pellagrous: due to low endogenous niacin synthesis. (Clinical symptoms similar to B2) Deficiency: Peripheral neuritis.

37 Deficiency a. Mild: irritability, nervousness, and depression b. Severe: peripheral neuropathy and convulsions, with occasional sideroblastic anemia c. Other symptoms: eczema and seborrheic dermatitis around the ears, nose, and mouth; chapped lips; glossitis; and angular stomatitis

Glycogenolysis METABOLISM OF AMINO ACIDS Racemization Transamination

38 Pyridoxol Pyridoxal Pyridoxal Phosphate Pyridoxamine Pyridoxamine Phosphate PYRIDOXAL AND PYRIDOXAMINE PHOSPHATE Pyridoxine (Vit B6) Glycogenolysis METABOLISM OF AMINO ACIDS Racemization Transamination Non-oxidative deamination DISEASE: Neuritis Isoniazid (to rx TB) Penicillamine

39 PANTOTHENIC ACID Source: very widespread in food Adequate intake (adults): 5 mg/d Function. Pantothenic acid is an essential component of coenzyme A (CoA) and the phosphopantetheine of fatty acid synthase Deficiency (very rare), with vague presentation that is of little concern to humans

40 COENZYME A Transfer of acyl groups Pantothenic acid NO DISEASE CoA-SH

41 Niacin (nicotinic acid) and niacinamide (nicotinamide)

42 Niacin (Vitamin B-3, nicotinic acid) Coenzymes: nicotinamide adenine dinucleotide (NADH) nicotinamide adenine dinucleotide phosphate (NADPH)

43 Sources & RDA Whole grain and enriched breads and cereals, milk, meats (liver, kidney, poultry) fish, legumes, groundnuts, and peanuts. Synthesized from dietary tryptophan. Part of the niacin requirement is met by synthesis of niacin from tryptophan. Corn is poor in niacin and tryptophan RDA: 14 to 16 mg of niacin or its equivalent (60 mg tryptophan = 1 mg niacin) Adults: 15-20mg/day Children: 10-15mg/day

45 Niacin Niacin is converted to the oxidation reduction coenzymes nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP). NAD+, NADH is an essential enzyme systems concerned with oxidation and reduction in living cells. Essential for carbohydrate, protein & fat metabolism. Essential for normal functioning of skin, intestinal & nervous system. Niacin or nicotinic acid is known as pellagra preventive(pp) factor.

46 Mild deficiency results in glossitis of the tongue. Severe deficiency or pellagra involves the skin (photosensitivity), gastrointestinal tract and central nervous system is characterized by the three Ds: dermatitis, diarrhea, and dementia and rarely the 4th D = Death Endemic in the southern US (corn belt) and many other parts of the world in the early 1900s, particularly among children. Pellagra was carried to Europe in the years following Columbus' discovery of the new world as maize (corn) was discovered and became the staple for Europe's poor. Largest outbreak since WW2 refugees in Malawi

48 Hartnup disease: caused by malabsorption of tryptophan

49 High doses (2 to 4 g/day) of nicotinic acid (not nicotinamide) result in vasodilation (very rapid flushing) and metabolic changes such as a decrease in blood cholesterol and low-density lipoproteins.

50 Therapeutic uses of niacin: Niacin is used as a drug to lowers cholesterol levels i) Inhibits lipolysis ii) Triacylglycerol synthesis in liver is decreased.

Diarrhea Depression Dementia Oxidation of one carbon atom

51 NIACIN (B3 or PP) NAD+ & NADP+ Nicotinic acid Nicotinamide PELLAGRA Glossitis Dermatitis Weight loss Diarrhea Depression Dementia Oxidation of one carbon atom Other Causes of Deficiency Hartnup disease Carcinoid syndrome Isoniazid

52 NICOTINAMIDE ADENINE DINUCLEOTIDE NAD+ Oxidation of one carbon atom Feed the Electron Transport Chain Hey, look at me!!!!

53 NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE NADP+ Oxidation of one carbon atom Most important source of reduction equivalent for synthesis Hey, look at me!!!!

54 Biotin

55 Sources and requirement: Biotin is present in most food such as organ meats, egg yolk, legumes, nuts, and chocolate. It is also synthesized by the intestinal bacterial flora. A recommended allowance has not been established. Adequate intake: 30 rig/day. Biotin supplements are required during prolonged parenteral nutrition and in patients given long-term high-dose antibiotics. Biotin has no toxicity.

56 Function Covalently linked biotin (biocytin) is the prosthetic group for carboxylation enzymes (e.g. pyruvate carboxylase, acetyl CoA carboxylase). carrier of activated CO2 (carboxyl transfer) participates in conversion of pyruvate to oxaloacetate (gluconeogenesis) and in fatty acid synthesis

57 Nutritional biotin deficiency is rare a. Signs and symptoms include dermatitis, hair loss (alopecia), atrophy of the lingual papillae, gray mucous membranes, muscle pain, paresthesia, hypercholesterolemia,and electrocardiographic abnormalities. b. Raw egg whites induces a biotin deficiency because it contains a protein avidin, that specifically binds biotin in a nondigestible form that prevent its absorption from the intestine. People who consume approximately 20 egg whites per day may develop biotin deficiency. Patients on long term high dose antibiotics without biotin suplementation also get biotin deficiency

58 ALOPECIA

59 BIOTIN Biocitin ATP dependent carboxylation reactions Transcarboxylation DISEASE IS UNCOMMON Antibiotics Raw eggs (avidin) Deficiency of biotinidase Dermatitis Loss of hair Paralysis

60 The Hematopoietic Vitamins NO neuro symptoms Folic acid, B-12 Hematopoiesis + neuro symptoms

61 Folic acid (pteroylglutamic acid, folacin) Recommended name: FOLATE Alternative name: FOLACIN Coenzyme form: tetrahydrofolic acid Important for carbohydrate metabolism

62 Sources & RDA Main source is dark green leafy vegetable but also found in liver, kidney, meat, dairy products, egg, citrus fruits & whole grain cereals, lima beans, asparagus, nuts, legumes and yeast. Adult: 200 mcg/day Pregnancy: 400mcg/day Lactation: 300 mcg/day RDA: 400 mcg/day The minimum need for adults is believed to be approximately 0.05 mg per day. Higher levels are recommended for children and during pregnancy. No toxicity has been observed

63 2001 Brooks/Cole, a division of Thomson Learning, Inc. Thomson Learning is a trademark used herein under license. Folate (Folic Acid) Leafy green vegetables, legumes, liver, and some fruits are naturally rich in folate.

66 Folate (Folic acid) - involved in the synthesis of DNA, especially in newly formed cells - deficiency results in anemia and GI tract deterioration - in the developing fetus, neural tube defects have been linked to low folate levels

67 Biochemical function Polyglutamate derivatives of tetrahydrofolate derivatives serve as donors / coenzymes in transfer of onecarbon units in purine and pyrimidine biosynthesis thymidylate synthesis biosynthesis of aminoacids i.e conversion of homocysteine to methionine, and serine glycine interconversion

68 Deficiency occurs simply from a poor diet, Commonly found during pregnancy & lactation when the requirement increases. Inhibition of DNA synthesis This leads to an arrest of cells in S phase and a characteristic "megaloblastic" change in the size and shape of the nuclei of rapidly dividing cells (RBC precursors) Megaloblastic RBCs hemolytic anemia Often induced by anti-folate chemotherapy drugs (aminopterin, methotrexate) 50% and 70% of the birth defects in this country could be eliminated if all pregnant women took folic acid supplements during pregnancy. The average diet includes only about half the required amount

69 Deficiency signs and symptoms a. Megaloblastic anemia, similar to that of vitamin B12 deficiency, as a consequence of blocked DNA synthesis (with glossitis, cheilosis, diarrhoea, distension & flatulence b. Neural tube defects as a result of maternal folate deficiency (in some cases).deficiency in pregnant women may cause neural defects in foetus. c. Severe folate deficiency may cause infertility & sterility. d. Elevated blood homocysteine, which is associated with atherosclerotic heart disease, with folate and vitamin B6 deficiency (in some cases) e. Several drugs can lead to folate deficiency, including methotrexate (cancer chemotherapy), trimethoprim (antibacterial), pyrimethamine (antimalarial), and diphenylhydantoin and primidone (anticonvulsants).

70 TETRAHYDROFOLATE Transfer of one carbon atom fragment with different oxidation status Very important in the synthesis of nucleotides DISEASE: Megaloblastic anemia

71 COFACTORS FROM TETRAHYDROFOLATE

72 Vitamin B12 (cobalamin)

73 Sources & RDA Vitamin B12 is not found in plant foods because plants cannot synthesize B-12 It is the only vitamin which is synthesized by microorganisms & not by plants & animals. B12 comes from bacteria in animals. Intestinal bacteria can synthesize B-12 (in colon), but the site of synthesis does not allow absorption. Vegan Sources: nutritional yeast, fortified cereals, fortified soy milks and soy products Best sources meat,liver, kidney, fish, whole milk and other dairy products, eggs, oyster, shellfish, shrimp, pork and chicken. Only water-soluble vitamin that can be stored Liver is main storage site of vitamin B12, enough for a 3 year supply Normal adults: 1 mcg/day Lactation: 1.5 mcg/day Pregnancy: 1.5 mcg/day Infants & children: 0.2 mcg/day

74 Vit B12 is also known as anti-pernicious anemia vitamin Intrinsic factor produced in stomach facilitates transport from gut to blood To be utilized the B-12 must first be removed from the protein by acid hydrolysis in the stomach or trypsin digestion in the intestine. It then must combine with "intrinsic factor", a glycoprotein secreted by the stomach, which carries it to the ileum for absorption. Patients with pernicious anemia lack the intrinsic factor. Pernicious anemia in elderly patients may be caused by lack of gastric acid Deficiency of IF (can be autoimmune) can result in B12 deficiency Possible to get deficiency if vegetarian, but rare In food B-12 (extrinsic factor) usually occurs bound to protein.

75 Functions of Vitamin B12 (cobalamin) It has separate biochemical role, unrelated to folate, in synthesis of fatty acids in myelin. Catalyzes 1,2 shift of hydrogen atoms a. Deoxyadenosyl cobalamin is the coenzyme for the conversion (isomerisation) of methyl-malonyl CoA to succinyl CoA (methylmalonyl CoA mutase) in the metabolism of propionyl CoA. b.methylcobalamin is the coenzyme for methyl group transfer between tetrahy-drofolate and methionine (homocysteine methyl transferase) in the synthesis of methionine from homocysteine. (Transfer of methyl-group from N5-methyl tetrahydrofolate to homocysteine to form methionine.) c.formation of collagen d.facilitates absorbtion of iron from vegetable foods. e.inhibits nitrosamine formation by intestinal mucosa.

76 Causes of vitamin B12 deficiency Deficiencies of B-12 are extremely rare a. Intake of no animal products. Long-term vegetarians (vegans) are at risk for vitamin B12 deficiency. b. Severe malabsorption diseases. c. Impaired absorption [from achlorhydria (insufficient gastric hydrochloric acid), decreased secretion of gastric intrinsic factor, impaired pancreatic function] d. Up to 20 percent of older people may exhibit diminished B12 absorption and require supplements due to insufficient production of intrinsic factor and/or HCl in the stomach

77 Deficiency: In man there are two major symptoms associated with B-12 deficiency, hematopoietic and neurological. Hematopoietic megaloblastic anemia. Neurological progressive demyelination of nervous tissue.

78 Deficiency signs and symptoms Pernicious (megaloblastic) anemia similar to that in folate deficiency Neuronal degeneration & demyelination of nervous system with paresthesia (numbness and tingling of the extremities), with weakness and other neurologic changes Prolonged deficiency leads to irreversible nervous system damage. Infertility in animal species.

DISEASE: Pernicious anemia Megaloblastic anemia Nerve

81 B12 - ADENOSYL COBALAMINE REACTIONS: Metabolism of one carbon atom fragment Isomerization of methylmalonyl-coa DISEASE: Pernicious anemia Megaloblastic anemia Nerve demyelinization Elevated urine methylmalonate levels Rx is B12 injections

82 The B Vitamins--In Concert The B Vitamins are interdependent. The presence of one may affect the absorption, metabolism and excretion of another. A deficiency of one may affect the functioning or deficiency of another. A variety of foods from each food group will provide an adequate supply of all the B vitamins.

83 The B Vitamins--In Concert B Vitamin Roles Coenzymes involved directly or indirectly with energy metabolism Facilitate energy-releasing reactions Build new cells to deliver oxygen and nutrients for energy reactions

85 The B Vitamins--In Concert B Vitamin Deficiencies Deficiencies rarely occur singly except for beriberi and pellagra. Can be primary or secondary causes Glossitis and cheilosis are two symptoms common to B vitamin deficiencies. B vitamin toxicities can occur with supplements.

87 The B Vitamins--In Concert B Vitamin Food Sources Grains group provides thiamin, riboflavin, niacin and folate. Fruits and vegetables provide folate. Meat group provides thiamin, niacin, vitamin B6 and vitamin B12. Milk group provides riboflavin and vitamin B12.

Physiological Role: B-vitamins are coenzymes of many enzymes systems of body metabolism. Thiamine {B 1 }

Physiological Role: B-vitamins are coenzymes of many enzymes systems of body metabolism. Thiamine {B 1 } Food Constituents [continued] Micronutrients B-Vitamins The B group of vitamin {water soluble} includes: Thiamine: vitamin B 1, ant beriberi vitamin. Riboflavin: vitamin B 2. Niacin: nicotinic acid, PP