Vitamin B 5 Pantothenic Acid Vitamin B 5

Vitamin B 5 ( Pantothenic Acid)

Vitamin B 5 ( Pantothenic Acid) v. 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 B 5 is coenzyme A (Co. A). RDA: 7 -10 mg (4 Years and over) 3 -5 mg (less than 4 Years) Principal Sources in Food Principal dietary sources of vitamin B 5 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

Functions of vitamin B 5 Pantothenic acid is a part of Co. A 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 Ketoacids 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.

Symptoms of Vitamin B 5 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 Paresthesias Muscle aches Anemia Insomnia fatigue

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

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. Lupus erythematosus 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. Fatigue Arthritis

5. Wound healing operations. after trauma or 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 B 5 Formulation) is used topically in treatment of burns and itching. Wound healing

Vitamin B 6 (Pyridoxine)

Vitamin B 6 (Pyridoxine) v. 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 B 6. v. Vitamin B 6 converted in the body to its major active form: pyridoxal-5 -phosphate (PLP). The activation requires adequate zinc and riboflavin. v. Total body stores vitamin of low are (only B 6 about 150 mg) hence a steady supply of vitamin B 6 is essential to avoid its deficiency. v. Chemically it is a pyridine derivative. RDA 1. 2 – 1. 4 mg (Adult) 0. 6 mg (Infants less than 1 year) 2. 2 mg (During pregnancy and lactation)

Pyridoxol Pyridoxamine Pyridoxal Pyridoxic Acid DIFFERENT FORMS OF PYRIDOXINE

Sources of Vitamin B 6 Potatoes Banana Calf liver Lentils Trout Spinach

Functions of Vitamin B 6 PLP is a coenzyme involved in more than 100 metabolic reactions in the body including: ØProtein synthesis through interconversion of amino acids. ØConversion of tryptophan to niacin. ØIt helps in maintaing blood glucose within a normal range. When caloric intake is low, vitamin B 6 help to convert stored carbohydrate to glucose to maintain normal blood sugar levels. ØLipid metabolism: It is important in synthesis of lipids of myelin sheath surrounding nerves and also in production of polyunsaturated fatty acids of cell membranes. ØIt helps in hemoglobin synthesis and oxygen transport by red blood cells.

Symptoms of Vitamin B 6 Deficiency ØSkin 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. ØAbnormal brain-wave patterns, convulsions, and muscle twitching. ØDepression, irritability, anxiety, confusion, headache, and insomnia. Dermatitis Stomatitis Glossitis Abnormal brainwave patterns convulsion

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

People at high risk of vitamin B 6 Deficiency ØDuring rapid growth rate in childhood, adolesence, and during lactation and pregnancy; sharply increase in vitamin B 6 requirements. ØHigh protein intakes increase vitamin B 6 requirements. ØOlder people (little diets intake and less efficient absorption). ØMany common drugs (including oral contraceptive pills and theophylline) can reduce vitamin B 6 stores.

ØPeople with chronic digestive problems e. g. liver problems, diarrhea or irritable bowel syndrome (poor vitamin B 6 absorption). ØPeople with other chronic diseases, including asthma, coronary heart disease, diabetes, kidney failure, rheumatoid arthritis, and cancer of the breast, bladder, and lymph nodes. ØIndividuals with a poor quality diet or an inadequate B 6 intake. ØAlcohol consumption also promotes the destruction and loss of vitamin B 6 from the body. Liver

Uses of Vitamin B 6 in Prevention and Therapy 1. Treatment and prevention of deficiency and for people at high risk of deficiency of Vitamin B 6. 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. 1. 6. In Pregnancy-associated nausea and vomiting.

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.

Toxicity and side effects of vitamin B 6 v. Very high doses (1000 mg/day) for long time peripheral nerve conditions: numbness in hands and feet. v. Doses of vitamin B 6 not exceeding 500 mg/day, or higher doses for short periods (days to weeks), are nontoxic in healthy persons. v. Very high doses of vitamin B 6 during lactation may reduce milk production.

Vitamin B 6 –Drug Interaction Drug class Examples Mechanism of interaction Hydrazines Iproniazid, Isoniazid, hydralazine React with pyridoxal and PLP to form a hydrazone Antibiotic Cycloserine Reacts with PLP to form anoxime L-DOPA l-3, 4 dihydroxyphenylalanine Reacts with PLP to form tetrahydroquinoline Derivatives Chelator Penicillamine Reacts with PLP to form thiazolidine Alcohol Ethanol Increased catabolism of PLP, low plasma levels

VITAMIN B 7

Vitamin B 7 (BIOTIN) ØIt is 2 -Imidazolidinone tetrahydro- thiophene-4 - valeric acid. ØBiotin is a cofactor required for enzymes that are involved in carboxylation reactions e. g. acetyl-Co. A carboxylase and pyruvate carboxylase used in the metabolism of carbohydrates, lipids and amino acids ØRDA: 100 - 200 μg/day.

Principal Sources of Vitamin B 7 Calf liver Soybeans Whole wheat Milk & Egg Oat meal Mushrooms Avocado

Functions of Vitamin B 7 These functions are dependent on a biotin-containing enzymes: 1. Glucose synthesis (The key initial step in gluconeogenesis). 2. 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). 3. Amino acid metabolism (breakdown of amino acids, such as threonine, isoleucine, and methionine, for use as energy). 4. Cell division and growth (Biotin plays an important role in DNA synthesis).

Biotin Deficiency v. Biotin is found in numerous foods and also is synthesized by intestinal bacteria and deficiency of this vitamin is rare. v. 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.

BIOTIN DEFICIENCY SYMPTOMS Extreme exhaustion Grayish skin color Depression Drowsiness Hair loss Muscle pain Loss of appetite

Uses of Vitamin B 7 in Prevention and Therapy ØInherited syndromes of impaired biotin metabolism in children. ØAnticonvulsant therapy (Biotin supplements during chronic anticonvulsant therapy reduce the risk of biotin deficiency). ØDiabetes (Biotin supplements help control blood glucose). ØDermatologic 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). ØHair and nail disorders: People with dry, brittle hair and fingernails may benefit from biotin.

VITAMIN B 9 (FOLIC ACID)

RDA: 200 μg/day Therapy: 400 – 800 μg/day ØIt is a water soluble conjugate of pteridine base, paminobenzoic acid and glutamic acid or pteroylmonoglutamic acid. ØMost of folate absorbed from the diet is converted to the active form, tetrahydrofolate (THF) coenzyme. ØN 5 -methyl-THF is the major storage form in the body (~50% in liver): needs vitamin B 12 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

CHEMICAL STRUCTURE OF FOLIC ACID

FUNCTIONS OF VITAMIN B 9 THF derivatives act as coenzymes for C 1 -transfer (methyl, methylene, formyl or formimino group) during biosynthetic reactions which helps the following functions: 1. Production of RBCs through its role in creating heme (the iron containing substance in haemoglobin). 2. Production of WBCs. 3. Protein metabolism. It plays a central role in the interconversion of amino acids such as glycine, serine and methionine and the synthesis of structural and functional proteins.

4. Production of nucleotides (ATP, GTP, and d TMP) and thus nucleic 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 28 th day of pregnancy) cannot be completed without Vitamin B 9.

Major Symptoms of Vitamin B 9 Deficiency 1. 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 B 12 deficiency (characterized by abnormally large immature and dysfunctional erythrocytes) which causes fatigue, weakness, shortness of breath, decreased ability to concentrate. 2. Impairments in white blood cell development and leukopenia reduce immune responses to infection and/or cancer.

3. Impaired cell growth in the digestive tract, inflammation of tissues in the mouth, stomach, and intestine reduced absorption of nutrients. 4. 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

People at High Risk of Vitamin B 9 Deficiency 1. People who depend on processed food and neglect whole grains and vegetables. 2. Smoking. 3. Many chronic diseases and health status such as psoriasis, anemia, infections, cancer, fever, trauma, surgery, or burns sharply increase folate requirements. 4. Liver disease interferes with folate metabolism and increases excretion. 5. Rapid growth childhood, and adolescence. 6. Pregnancy. 7. Heavy alcohol consumption interferes with absorption, impairs conversion to THF, and increases excretion. 8. Deficiency of ascorbic acid. 9. Deficiency of vitamin B 12 impairs folate metabolism and produces signs of folate deficiency.

Uses of Folic Acid in Prevention and Therapy 1. 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. 2. Atherosclerosis: Folate help preventing atherosclerosis (heart attack, and peripheral vascular disease) in people with elevated homocysteine (THF with Vitamin B 12 detoxify homocysteine to methionine). 3. Enhance immunity in case of infections.

4. 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 B 12 can reduce dysplasia in the lungs of smokers and reduce the risk of lung cancer. 4. 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.

Folic Acid – Drug Interactions v. Drugs reduce folate level e. g. ØAspirin Øoral contraceptive pills ØAntacids ØAnticonvulsant Øantibiotics. v. Folic acid antagonists e. g. ØMethotrexate

VITAMIN B 12 (Cobalamin, Antipernicious anemia factor)

Vitamin B 12 1. Vitamin B 12 is a family of related compounds containing a cobalt atom (cobalamins). 2. The two dietary forms of vitamin B 12 are available and they are known as methylcobalamin (meth yl. B 12) and 5 - deoxyadenosylcobalamin (coenzyme. B 12). 3. Synthetic forms of vitamin B 12 are known as hydroxy-cobalamin and cyanocobalamin (not occur naturally in foods). 4. Structure of B 12 is very complicated and based on a corrin ring, similar to porphyrin ring found in heme, chlorophyll, and cytochrome.

A B D C Vitamin B 12

5. The central metal ion is cobalt (Co) which coordinates with nitrogens of corrin ring and that of dimethylbenzimidazole group. 6. The sixth coordination can be : CN- (in Cyanocobolamin), HO- (in Hydroxycobalamin), CH 3 (in Methylcobalamin, Me-B 12), deoxyadenosyl group (Adenosylcobalamin, Ado. B 12 = coenzyme-B 12). 7. Very small amounts of vitamin B 12 are stored in our bodies, about 90% of which (2– 5 mg) is stored in the liver and is sufficient for 2 years.

Sources of vitamin B 12 The intestinal flora produces the vitamin required for man and animals. Vitamin B 12 can be obtained from animal diet only. Principal Sources in Food Principal dietary sources of vitamin B 12 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 1 -3 4 -8 9 – 13 14 – 18 >18 μg/day 0. 9 1. 2 1. 8 2. 4

Absorption of vitamin B 12 Ø Vitamin B 12 in food is bound to protein. Ø HCl of the stomach releases the free vitamin B 12. Ø Once released, vitamin B 12 combines with glycoprotein intrinsic factor (IF) secreted by the parietal cells of stomach to form a complex which can be absorbed from ileum.

Functions of Vitamin B 12 1. Essential with folic acid in RBCs maturation (it protects against Pernicious anemia). 2. Folate metabolism. Vitamin B 12 is vital in activation of folate to the active THF. In vitamin B 12 deficiency, tissue stores of folate are “trapped” as inactive methylated forms, and a functional folate deficiency results. 3. Protein metabolism: Act as coenzyme with THF in the synthesis of methionine from homocysteine.

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.

People at High Risk of Vitamin B 12 Deficiency 1. Eldery people: Gastric secretion and intrinsic factor is diminished. Both are required for optimum vitamin B 12 absorption. 2. People suffering from chronic gastritis with atrophy of the parietal cells that produce intrinsic factor. 3. Intestinal diseases e. g. chronic enteritis with diarrhea reduce absorption of vitamin B 12. 4. Liver disease impair vitamin B 12 status (as the liver is the site of vitamin B 12 storage and the site of production of specific transport proteins). 5. Strict vegetarian diets (devoid of animal products). 6. Cigarette smoking impairs vitamin B 12 status.

Major Symptoms of Vitamin B 12 Deficiency 1. 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. 2. Neurological changes such as numbness and tingling in the hands and feet (due to diminished myelination). 3. Difficulty in maintaining balance, depression, confusion, dementia, poor memory.

4. Reduced platelet production (increase risk of abnormal bleeding). 5. Impaired white blood cell development reduces immune responses to infection and/or cancer. 6. 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.

Uses of Vitamin B 12 in Prevention and Therapy 1. Treat and prevent deficiency conditions and pernicious anemia (a condition in which the body can't make enough healthy red blood cells). 2. In combination with folate to treat megaloblastic anemia. 3. Treatment of psychiatric/nervous disorders e. g. dementia and memory loss, particularly in the elderly people. 4. It is helpful with folate in prevention and therapy of atherosclerosis associated with high levels of blood homocysteine. 5. It is helpful with folate to reduce smoking-induced precancerous cells in the lungs reducing risk of lung cancer.

6. Reduction of peripheral nerve disorders e. g. neuropathy in diabetics, trigeminal neuralgias and traumatic nerve injuries. 7. Large doses (5 - 10 g IV) of Hydroxycobalamin used in cyanide poisoning where it combine with cyanide ion to form harmless Cyanocobalamin. In pernicious anemia, vitamin B 12 should be given as IM injection (100 to 1000 μg of cyanocobalamin for 5 days followed by 100 to 1000 μg each month) till correction of blood picture.

Vitamin B 12 – Drug Interaction ØSome Drugs interfere with its absorption such as: v. Alcohol vp-aminosalicylic acid v. Colchicine v. Neomycin v. Cholestyramine v. Anticonvulsants (Phenytoin) v. Metformin ØH 2 blockers include cimetidine, proton pump inhibitors e. g. omeprazole reduce secretion of gastric acid and pepsin reduce isolation and absorption of protein-bound (dietary) vitamin B 12.

THANX