Vitamin B5 ( Pantothenic Acid)

1. Vitamin B5 ( Pantothenic Acid)

2. Vitamin B5 ( Pantothenic Acid) • It is a peptide composed of D-Pantoic acid and β-Alanine and is found as calcium salt or as alcohol (Pantothenol). The biologically active form of Vitamin B5 is coenzyme A (CoA). RDA: 7-10 mg (4 Years and over) 3-5 mg (less than 4 Years) Principal Sources in Food Principal dietary sources of vitamin B5 include: Food Serving size mg Calf liver 100 g 7.9 Pea nuts 100 g 2.6 Peas 100 g 2.1 Soybeans 100 g 1.9 Brown rice 100 g 1.7 lobster 100 g 1.7 Water melon 100 g 1.6 Egg 1, Avg size 0.9 Brewer’s Yeast 10 g 0.7 Pantothenic acid Pantothenol

3. Functions of vitamin B5 • Pantothenic acid is a part of CoA that acts as an intracellular carrier for few carbons-groups and assists more than 100 pathways of intermediate metabolism including those of: • 1. Synthesis of Sterols (Cholesterol and 7- Dehydrocholesterol), Fatty acids, and Keto- acids such as Pyruvic acid. • 2. Energy production • 3. Synthesis of vitamins A and D. • 4. Biosynthesis of protein and amino acid by assisting the formation of leucine, arginine, and methionine. • 5. It is essential for the formation of hemoglobin and electron-carrying cytochrome proteins of the mitochondrial respiratory chain. • 6.Biosynthesis of the neurotransmitter acetylcholine.

4. Symptoms of Vitamin B5 Deficiency 1.Paresthesias (It is a sensation of tingling, pricking, or numbness of a person's skin) and burning sensation in lower legs and feets. 2. Joint and muscle aches 3. Fading of hair color 4. Anemia 5.Reduced immunity: impaired antibody response 6. Headache, depression, insomnia, and fatigue Anemia fatigue Paresthesias Muscle aches Insomnia

5. People at high risk of Vitamin B5 Deficiency • Pantothenic acid is widely prevalent in foods, subclinical deficiency only may occur, usually in conjunction with other B-vitamin deficiencies in case of: • Chronic illness • Heavy alcohol consumption • During hypocaloric dieting for weight-loss.

6. Uses of Pantothenic acid in Prevention and Therapy 1.Microcytic anemia (through its role in hemoglobin synthesis in conjunction with iron supplementation). 2.Lupus erythematosus: Calcium pantothenate, alone or in conjunction with vitamin E can help in treatment of Lupus erythematosus and other autoimmune disorders. 3.Tiredness and fatigue as those associated with subclinical pantothenic acid. 4.Arthritis: Pantothenic acid deficiencies are often found in patients with osteoarthritis and rheumatoid arthritis. In this case calcium pantothenate can be effective. Lupus erythematosus Fatigue Arthritis

7. 5.Wound healing after trauma or operations. 6.Management of dyslipidemia (abnormal amount of lipids e.g. cholesterol and/or fat, in the blood). 7. Diabetic neuropathy (kidney disease or damage that can occur in people with diabetes). 9. Dexapantothenol (vitamin B5 Formulation) is used topically in treatment of burns and itching . Wound healing

8. Vitamin B6 (Pyridoxine)

9. Vitamin B6 (Pyridoxine) • In 1934, a Hungarian physician, Paul Gyorgy discovered a substance that was able to cure a skin disease in rats (Dermititis acrodynia), this substance he named vitamin B6. • Vitamin B6 converted in the body to its major active form: pyridoxal-5-phosphate(PLP). The activation requires adequate zinc and riboflavin. • Total body stores of vitamin B6 are low (only about 150 mg) hence a steady supply of vitamin B6 is essential to avoid its deficiency. • Chemically it is a pyridine derivative. RDA 1.2 – 1.4 mg (Adult) 0.6 mg (Infants less than 1 year) 2.2mg (During pregnancy and lactation)

10. Pyridoxal Pyridoxol Pyridoxamine Pyridoxic Acid DIFFERENT FORMS OF PYRIDOXINE

11. Sources of Vitamin B6 Potatoes Banana Calf liver Spinach Trout Lentils

12. Functions of Vitamin B6 • PLP is a coenzyme involved in more than 100 metabolic reactions in the body including: • Protein synthesis through interconversion of amino acids. • Conversion of tryptophan to niacin. • It helps in maintaing blood glucose within a normal range. When caloric intake is low, vitamin B6 help to convert stored carbohydrate to glucose to maintain normal blood sugar levels. • Lipid metabolism: It is important in synthesis of lipids of myelin sheath surrounding nervesand also in production of polyunsaturated fatty acids of cell membranes. • It helps in hemoglobin synthesis and oxygen transport by red blood cells.

13. Symptoms of Vitamin B6 Deficiency • Skin disorders: Dermatitis (skin inflammation), Stomatitis (inflammation of the mucous lining of any of the structures in the mouth), Glossitis (is inflammation or infection of the tongue ), and Painful fissures and cracks at the angles of the mouth and on the lips. • Abnormal brain-wave patterns, convulsions, and muscle twitching. • Depression,irritability, anxiety, confusion, headache, and insomnia. Glossitis Abnormal brain- wave patterns Dermatitis Stomatitis convulsion

14. Anemia and decreased antibody production • Possible increased risk of atherosclerosis due to increased total cholesterol and LDL- cholesterol in the blood, and reduced levels of HDL-cholesterol. • Possible increased risk of calcium-oxalate kidney stones. Anemia Atherosclerosis Kidney stones.

15. People at high risk of vitamin B6 Deficiency • During rapid growth rate in childhood, adolesence, and during lactation and pregnancy; sharply increase in vitamin B6 requirements. • High protein intakes increase vitamin B6 requirements. • Older people (little diets intake and less efficient absorption). • Many common drugs (including oral contraceptive pills and theophylline) can reduce vitamin B6 stores.

16. People with chronic digestive problems e.g. liver problems, diarrhea or irritable bowel syndrome (poor vitamin B6 absorption). • People with other chronic diseases, including asthma, coronary heart disease, diabetes, kidney failure, rheumatoid arthritis, and cancer of the breast, bladder, and lymph nodes. • Individuals with a poor quality diet or an inadequate B6 intake. • Alcohol consumption also promotes the destruction and loss of vitamin B6 from the body. Liver

17. Uses of Vitamin B6 in Prevention and Therapy • 1.Treatment and prevention of deficiency and for people at high risk of deficiency of Vitamin B6. • 2.Skin disorders(eruptions, acne etc.). • 3. Reduction of the severity and frequency of bronchial asthma. • 4.Atherosclerosis and cardio-vascular disease (It reduces tendency for platelets to clump together, lowers LDL-cholesterol and raises HDL cholesterol. • 5. In certain anemia, alone or with iron and vitamin A. • 6. In Pregnancy-associated nausea and vomiting.

18. 7. Premenstrual syndrome (It helps prevention of mood swings, edema, acne, and breast tenderness characteristic of PMS) 8. Arthritis(it helps in reduction of swelling and inflammation in the joints of the fingers). 9. Nerve disorders e.g. carpal tunnel syndrome (occurs when the median nerve, which runs from the forearm into the palm of the hand, becomes pressed or squeezed at the wrist) and other forms of nerve inflammation and neuropathy.

19. Toxicity and side effects of vitamin B6 • Very high doses (1000mg/day) for long time peripheral nerve conditions: numbness in hands and feet. • Doses of vitamin B6 not exceeding 500mg/day, or higher doses for short periods (days to weeks), are nontoxic in healthy persons. • Very high doses of vitamin B6 during lactation may reduce milk production.

20. Vitamin B6 –Drug Interaction

21. VITAMIN B7

22. Vitamin B7 (BIOTIN) • It is 2-Imidazolidinone tetrahydro- thiophene-4- valeric acid. • Biotin is a cofactor required for enzymes that are involved in carboxylation reactions e.g. acetyl-CoA carboxylase and pyruvate carboxylase used in the metabolism of carbohydrates, lipids and amino acids • RDA: 100- 200 μg/day.

23. Principal Sources of Vitamin B7 Soybeans Whole wheat Calf liver Milk & Egg Mushrooms Avocado Oat meal

24. Functions of Vitamin B7 These functions are dependent on a biotin-containing enzymes: Glucose synthesis (The key initial step in gluconeogenesis). Fat metabolism (synthesis and breakdown of fatty acids as well as the essential fatty acid metabolism such as conversion of linoleic acid to various eicosanoids). Amino acid metabolism (breakdown of amino acids, such as threonine, isoleucine, and methionine, for use as energy). Cell division and growth(Biotin plays an important role in DNA synthesis).

25. Biotin Deficiency • Biotin is found in numerous foods and also is synthesized by intestinal bacteria and deficiency of this vitamin is rare. • Deficiencies are generally seen only after long antibiotic therapies which deplete the intestinal flora or with anticonvulsant therapy, and excessive consumption of raw eggs (a biotin antagonist). The egg white protein, avidin, prevents intestinal absorption of the biotin.

26. BIOTIN DEFICIENCY SYMPTOMS Extremeexhaustion Drowsiness Muscle pain Hair loss Loss of appetite Grayish skin color Depression

27. Uses of Vitamin B7 in Prevention and Therapy • Inherited syndromes of impaired biotin metabolism in children. • Anticonvulsant therapy (Biotin supplements during chronic anticonvulsant therapy reduce the risk of biotin deficiency). • Diabetes (Biotin supplements help control blood glucose). • Dermatologic disorders e.g. Seborrheic dermatosis, acne, and other forms of scaly skin rash can respond to biotin, particularly when taken as part of a complete vitamin B complex in conjunction with essential fatty acids (omega-6 and omega-3 fatty acids). • Hair and nail disorders: People with dry, brittle hair and fingernails may benefit from biotin.

28. VITAMIN B9 (FOLIC ACID)

29. RDA: 200 μg/day Therapy: 400 – 800 μg/day • It is a water soluble conjugate of pteridine base, p-aminobenzoicacid and glutamic acid or pteroylmonoglutamic acid. • Most of folate absorbed from the diet is converted to the active form, tetrahydrofolate (THF) coenzyme. • N5-methyl-THF is the major storage form in the body (~50% in liver): needs vitamin B12 to be active. Principal Sources in Food Principal dietary sources of biotin include: Food Serving size μg Calf liver 100 g 108 Soybeans 100 g 95 Brewer’s Yeast 10 g 92 Wheat germ 100 g 270 Egg 1, Avg size 100 Spinach 100 g 134 Broccoli 100 g 105

30. CHEMICAL STRUCTURE OF FOLIC ACID

31. FUNCTIONS OF VITAMIN B9 THF derivatives act as coenzymes for C1-transfer (methyl, methylene, formyl or formimino group) during biosynthetic reactions which helps the following functions: Production of RBCs through its role in creating heme (the iron containing substance in haemoglobin). Production of WBCs. Protein metabolism. It plays a central role in the interconversion of amino acids such as glycine, serine and methionineand the synthesis of structural and functional proteins.

32. Production of nucleotides (ATP, GTP, and d TMP) and thusnucleic acids: DNA and RNA which are essential for growing and dividing cells. Therefore, cells that rapidly turn over and are replaced, such as blood cells and cells lining the digestive tract, are particularly dependent on THF. • 5. Proper formation of the brain, spinal cord, and nerve cells (CNS) in the embryo. Closure of the neural tube in the fetus (in the 28th day of pregnancy) cannot be completed without Vitamin B9.

33. Major Symptoms of Vitamin B9 Deficiency The most pronounced effect of folate deficiency on cellular processes is upon DNA synthesis (due to an impairment in d TMP synthesis) arrest of cell cycle of rapidly proliferating cells, particularly, the RBCs resulted in occurrence of megaloblastic anemia as for vitamin B12 deficiency (characterized by abnormally large immature and dysfunctional erythrocytes) which causes fatigue, weakness, shortness of breath, decreased ability to concentrate. Impairments in white blood cell development and leukopenia reduce immune responses to infection and/or cancer.

34. Impaired cell growth in the digestive tract, inflammation of tissues in the mouth, stomach, and intestine reduced absorption of nutrients. • Impaired fetal growth and development, birth defects such as Neural Tube Defects (NTDs) e.g. Spina bifida. Megaloblastic anemia Leucopenia Neural Tube Defects e.g. Spina Bifida (SB) SB occurs when two sides of the spine fail to close and protect spinal cord

35. People at High Risk of Vitamin B9 Deficiency People who depend on processed food and neglect whole grains and vegetables. Smoking. Many chronic diseases and health status such as psoriasis, anemia, infections, cancer, fever, trauma, surgery, or burns sharply increase folate requirements. Liver disease interferes with folate metabolism and increases excretion. Rapid growth childhood, and adolescence. Pregnancy. Heavy alcohol consumption interferes with absorption, impairs conversion to THF, and increases excretion. Deficiency of ascorbic acid. Deficiency of vitamin B12 impairs folate metabolism and produces signs of folate deficiency.

36. Uses of Folic Acid in Prevention and Therapy • Prophylaxis from birth defects: • Supplemental folate (400μg/day) days before conception and during early pregnancy reduces the risk of birth defects, particularly neural tube defects, cleft lip and palate. • Atherosclerosis: • Folate help preventing atherosclerosis (heart attack, and peripheral vascular disease) in people with elevated homocysteine (THF with Vitamin B12 detoxify homocysteine to methionine). • 3. Enhance immunity in case of infections.

37. Cancer: • Folate supplements may also reduce the risk of colon cancer in people with inflammatory bowel diseases. Folate + vitamin A can reduce the risk of cervical dysplasia (abnormal changes in the cells on the surface of the cervix) progressing to cervical cancer. Folate + vitamin B12 can reduce dysplasia in the lungs of smokers and reduce the risk of lung cancer. • Psychiatric/nervous disorders: • Symptoms of dementia in elderly people may be improved by folic acid supplementation. Folate can be adjunctive therapy with lithium in the treatment of manic- depressive illness.

38. Folic Acid – Drug Interactions • Drugs reduce folate level e.g. • Aspirin • oral contraceptive pills • Antacids • Anticonvulsant • antibiotics. • Folic acid antagonists e.g. • Methotrexate

39. VITAMIN B12 (Cobalamin, Antipernicious anemia factor)

40. Vitamin B12 Vitamin B12 is a family of related compounds containing a cobalt atom (cobalamins). The two dietary forms of vitamin B12 are available and they are known as methylcobalamin (meth yl-B12)and 5- deoxyadenosylcobalamin (coenzyme-B12). Synthetic forms of vitamin B12 are known as hydroxy-cobalamin and cyanocobalamin (not occur naturally in foods). Structure of B12 is very complicated and based on a corrin ring, similar to porphyrin ring found in heme, chlorophyll, and cytochrome.

41. A B D C Vitamin B12

42. The central metal ion is cobalt (Co) which coordinates with nitrogens of corrin ring and that of dimethylbenzimidazole group. • The sixth coordination can be : CN- (in Cyanocobolamin), HO- (in Hydroxycobalamin), CH3 (in Methylcobalamin, Me-B12), deoxyadenosyl group (Adenosylcobalamin, Ado-B12 = coenzyme-B12). • Very small amounts of vitamin B12 are stored in our bodies, about 90% of which (2–5 mg) is stored in the liver and is sufficient for 2 years.

43. Sources of vitamin B12 The intestinal flora produces the vitamin required for man and animals. Vitamin B12 can be obtained from animal diet only. Principal Sources in Food Principal dietary sources of vitamin B12 include: Food Serving size μg Calf liver 100 g 60 Egg 1, Avg size 1 Beef 100 g 2 Milk 1, large glass 0.4 Hard Cheese 30 g 0.6 Mussels 100 g 8 Required Daily Amount (RDA) Age μg/day 1 - 3 0.9 4 - 8 1.2 9 – 13 1.8 14 – 18 2.4 >18 2.4

44. Absorption of vitamin B12 • Vitamin B12 in food is bound to protein. • HCl of the stomach releases the free vitamin B12. • Once released, vitamin B12 combines with glycoprotein intrinsic factor (IF) secreted by the parietal cells of stomach to form a complex which can be absorbed from ileum.

45. Functions of Vitamin B12 Essential with folic acid in RBCs maturation (it protects against Pernicious anemia). Folate metabolism. Vitamin B12 is vital in activation of folate to the active THF. In vitamin B12 deficiency, tissue stores of folate are “trapped” as inactive methylated forms, and a functional folate deficiency results. Protein metabolism: Act as coenzyme with THF in the synthesis of methionine from homocysteine.

46. 4. It is vital in fat metabolism. 5. Helps maintain the antioxidant status by maintaining glutathione in the reduced form. 6. Nervous system (It is vital in synthesis of myelin sheath of neurons). 7. Cell replication. It is essential with THF in synthesis of nucleic acids.

47. People at High Risk of Vitamin B12 Deficiency Eldery people: Gastric secretion and intrinsic factor is diminished. Both are required for optimum vitamin B12 absorption. People suffering from chronic gastritis with atrophy of the parietal cells that produce intrinsic factor. Intestinal diseases e.g. chronic enteritis with diarrhea reduce absorption of vitamin B12. Liver disease impair vitamin B12 status (as the liver is the site of vitamin B12 storage and the site of production of specific transport proteins). Strict vegetarian diets (devoid of animal products). Cigarette smoking impairs vitamin B12 status.

48. Major Symptoms of Vitamin B12 Deficiency Pernicious Anemia: It is a case of megaloblastic anemia caused by atrophic gastritis and parietal cell loss and characterized by neuropathy: ease fatigue, weakness, shortness of breath, decreased ability to concentrate, and peripheral nerve damage. Neurological changes such as numbness and tingling in the hands and feet (due to diminished myelination). Difficulty in maintainingbalance, depression, confusion, dementia, poor memory.

49. Reduced platelet production (increase risk of abnormal bleeding). • Impaired white blood cell development reduces immune responses to infection and/or cancer. • Impaired cell replication leads to atrophy and inflammation of mucous membranes in the mouth, tongue and GIT, reduced absorption of nutrients, constipation, anorexia, and weight loss.

50. Uses of Vitamin B12 in Prevention and Therapy Treat and prevent deficiency conditions and pernicious anemia (a condition in which the body can't make enough healthy red blood cells). In combinationwith folate to treat megaloblastic anemia. Treatment of psychiatric/nervous disorders e.g. dementia and memory loss, particularly in the elderly people. It is helpful with folate in prevention and therapy of atherosclerosis associated with high levels of blood homocysteine. It is helpful with folate to reduce smoking-induced precancerous cells in the lungs reducing risk of lung cancer.