VITAMINS

-Essential exogenous factors Classification Fat soluble vitamins A,D,E and K Water soluble vitamins C and B complex B complex Oxido-reductive vitamins Niacin, Riboflavin Hematopoietic vitaminsFolic acid and Cobalamin Group transferring vitamins Thiamine, Pyridoxine, Biotin & Pantothenic acid Vitamin like substancesLipoic acid, Inositol, Choline & PABA

Thiamine (B1)
Sources Outer coatings of seeds/grains Vegetables, fruits, Meat, fish, egg, milk RDA (Recommended dietary allowances) Thiamin RDA Carbohydrate intake Adults- 1-1.5mg Pregnancy, Lactation ~ 2mg

Structure
Thiamine

Thiamine pyrophosphate

Biochemical role
Coenzyme Thiamine pyrophosphate (TPP) 2 types of reactions Oxidative decarboxylation Transketolase

Oxidative decarboxylation
Pyruvate dehydrogenase complex - Keto glutarate dehydrogenase complex Branched chain keto acid dehydrogenase complex

Mechanism

Thiamine deficiency
Causes Malnutrition Polished rice as staple diet Chronic alcoholism Thiamine antagonists pyri & oxy thiamine Consumption of raw fishes (certain type)

 Deficiency manifestations
BERI BERI Wet Beri Beri Edema, CVS problems, Palpitation & Dyspnea Dry Beri Beri No edema, CNS problems, Muscle wastage & peripheral neuritis Mixed Beri Beri Infantile Beri Berisleeplessness,vomiting,convulsion

 Cerebral Beri Beri (Wernicke Korsakoff syndrome) Initial stage - Psychosis (mental confusion, impaired cognitive abilities) Later stage - Encephalopathy Ophthalmoplegia, Nystagmus, cerebellar ataxia Seen in chronic alcoholics

Biochemical parametersBlood B1, RBC Transketolase activity (TPP effect) Blood Pyruvate, Lactate & - Keto glutarate (Lactic acidosis) B1 load test ( Saturation test )

Riboflavin ( B2 )
Sources: Yeast, egg, milk, meat, germinating grams and dals RDA Adults- 1- 1.5mg P/L ~ 2mg

 Riboflavin Isoalloxazine + Ribitol

Biological role Coenzyme 2 forms FMN ( Flavin Mono Nucleotide) FAD ( Flavin Adenine Dinucleotide)

 Formation

 FMN dependent enzymes L-Amino acid Oxidase

FAD dependent enzymes D-Amino acid Oxidase Succinate Dehydrogenase Acyl CoA Dehydrogenase Xanthine Oxidase Oxidative decarboxylation-PDH

Riboflavin deficiency
Causes Malnutrition Photo therapy for neonatal Jaundice Manifestations Glossitis
Magenta colored tongue Fissures of tongue Atrophy of lingual papillae

Cheilosis Angular stomatitis Seborrheic dermatitis Corneal vascularisation- Burning watery eyes

Vitamin C ( Ascorbic acid ) Sources Citrus fruits , Green vegetables, milk is a poor source. RDA Adults ~ 75 90 mg P/L ~ 100 mg

 --

Biochemical role
Formation of supporting tissues of mesenchymal origin Collagen, Osteoid, Dentine & Intercellular substance Cofactor for Hydroxylases
Hydroxylation of Proline and Lysine residues of proto collagen

Tyrosine catabolism PHPP Hydroxylase Formation of catecholamines (dopamine hydroxylase) Serotonin formation(tryptophan hydroxylase) Carnitine formation Cholesterol catabolism (7 alpha hydroxylase) lfa-Oxidation of fatty acids Role in Iron & Hemoglobin metabolism(ferritin formation) Role in cellular respiration Role in Folate metabolism(folate reductase ) Immunological function Antioxidant Preventive action on cataract

Vitamin C deficiency
Scurvy Infantile scurvy (Barlows disease) Symptoms Loosening of teeth Spongy bleeding gums Delay in wound healing Bleeding at joint regions Subcutaneous hemorrhage Demineralization of bone Frequent fractures Arrested skeletal growth Poor development of teeth Microcytic hypochromic anemia

Hypervitaminosis C
Prolonged excess intake (1000-2000mg /day)
Renal calculi ??????

Niacin ( B3 )/Nicotinic acid/ Nicotinamide

Sources Yeast, Rice polishings, Peanuts, Cereals, Legumes, milk,

Meat, fish etc

RDA Adults ~ 15 mg , P/L ~ 22-25 mg Depends on tryptophan content in the diet ( 60 mg Tryptophan 1 mg NAD+ ) Structure

Biochemical role
Coenzyme 2 forms NAD+ (Nicotinamide Adenine Dinucleotide) NADP+ (Nicotinamide Adenine Dinucleotide Phosphate)

 Enzymes involved in the conversion of Niacin to NAD /NADP

Niacin phosphoribosyl transferase NAD Pyrophosphorylase NAD synthetase NAD kinase

 Role in redox reactions

NAD+ dependent enzymes LDH Glyceraldehyde-3-phosphate DH PDH -Keto glutarate DH Isocitrate DH MDH eta-Hydroxy acyl CoA DH Glycero phosphate DH

NADPH producing reactrions Glucose-6-phosphate DH 6-phospho Gluconate DH Cytosolic Isocitrate DH Malic enzyme ( malate pyruvate )
NADPH using reactions Biliverdin Reductase HMG CoA Reductase -Keto acyl Reductase Enoyl Reductase Dihydro Biopterin reductase Folate Reductase Glutamate DH NAD(P)+

Niacin deficiency
Causes
Malnutrition Consumption of Maize( Corn) as staple diet (bound form) Sorghum (Jowar / Guinea corn) as staple diet (Leucine pellagra) Nutritional deficiency of pyridoxine Isoniazid (INH) therapy Hartnups Disease Carcinoid syndrome

Niacin deficiency
Pellagra Charateristics 3Ds
Dermatitis- Casals necklace Diarrhoea Dementia
Mild
Irritability Lack of concentration Poor memory

Chronic
Ataxia Spasticity

Leucine Pellagra

Pyridoxine (B6)
Sources Yeast, rice polishings, Cereals,Legumes, milk,meat, fish & Green Veg RDA Related to protein intake Adults ~ 1.5 mg P/L ~ 2.5 mg

 3 Vitamers

 Biochemical role Coenzyme Pyridoxal phospahte (PLP)

Pyridoxal Kinase B6 to PLP Remains bound to apoenzymes through Schiff base linkage and Salt bridges

Reactions
Transamination
AST & ALT

Decarboxylation
Glutamate Decarboxylase Histidine Decarboxylase 5-Hydroxy Tryptophan Decarboxylase Dopa Decarboxylase

Methionine Metabolism
Cystathionine Synthase Cystathionine Lyase

Heme Biosynthesis
-ALA Synthase

 Tryptophan Catabolism
Kynureninase

Glycine metabolism
Glycine hydroxy methyl transferase

Glycogenolysis
Glycogen Phosphorylase

Non oxidative deamination

Serine Dehydratase

Deficiency
Causes

Malnutrition Isoniazid Therapy Pencillamine & Cyclo serine Antagonists Alcoholism Oral contraceptives & steroids
Neurological problems Epileptic seizures Hypochromic microcytic anemia Pellagra like symptoms Synovial swelling and tenderness (Carpal tunnel disease)

Symptoms

B6 Deficiency assessment

Tryptophan load test Methionine load test RBC transaminase activity

Folic acid
Sources- Spinach, cabbage,green leafy vegetables Cereals, pulses & egg , milk is rather a poor source RDAAdults ~ 400 g P ~ 500- 600 g L ~ 500 g

Diet

Folacin

Folic acid

Absorbed

Intestinal Folyl polyglutamate hydrolase (Folate conjugase) Biological role Coenzyme - Tetrahydrofolate (H4F/THF) Formation

One carbon Metabolism -CH3 -CH2 -CH= -CHO -CH=NH

Different forms of THF with different one carbon groups

N5,N10 methylene THF

Serine hydroxymethyl transferase Glycine synthase Thymidilate synthetase

N5,N10-Methenyl THF N10-Formyl THF N5- Formimino THF N5- Methyl THF N5-Formyl THF Folinic acid Citrovorum factor

Purine biosynthesis Purine Biosynthesis Histidine cataboilsm

Vitamin B12 / Homocysteine metabolism

Folate deficiency

Causes
Malnutrition Increased requirement
Pregnancy Hemolytic anemia

Malabsorption
Fish tape worm infestation Tropical Sprue Anti-convulsant drugs / Oral contraceptives

Functional deficiency Drugs(Folate antagonists)

Methotrexate, Aminopterin, pyrimethamine, Trimethoprim, Sulfanamide

B12 deficiency Folate trap

Folate deficiency

Manifestations
Macrocytic anemia Important for proper neural development during fetal growth - spina bifida FIGLU excretion test

Pantothenic acid (B5)

SourcesYeast, liver, egg,milk, cereals & legumes Bacterial floral synthesis RDA Adults ~ 5 mg P/L ~ 10-15 mg Structure -

 Biochemical role Coenzyme CoA / CoASH ( Coenzyme A )

Cysteine

Bio-role
Oxidative decarboxylation
Pyruvate DH complex -Keto glutarate DH complex

Component of Acetyl CoA, Succinyl CoA, Propionyl CoA Role in Fatty acid oxidation Role in fatty acid biosynthesis Deficiency Rare Gopalans Burning feet syndrome
Burning/lightning sensation in the feet Numbness of toes Staggering gait sleeplessness

Biotin Vitamin H
Sources Yeast, liver, egg,milk, cereals & legumes Bacterial floral synthesis RDA Adults ~300 g

Structure of biotin

Biocytin

 Biotin reactions
Pyruvate carboxylase Acetyl CoA carboxylasae Propionyl CoA carboxylase Leucine metabolism

Biotin independent carboxylations-carbamoyl P Deficiency

Rare Consumption of raw eggs Avidin Prolonged use of antibiotics

 Deficiency symptoms
Dermatitis Atrophic glossitis/anorexia Muscular pain Neurological defects In coordinated movements

Cobalamin B12
Sources Meat, fish, pork, chicken
Milk, curds Micro organisms, yeast

RDA
Adults ~ 2.5 g P/L ~ 4 g

B12 Structure
Corrin ring
4 Pyrrole rings ( similar to Porphyrin ring) C-C Bond between A & D rings Different side chains Cobalt at the center

Cobalt - Attached to 4 nitrogen atoms & DMB(dimethyl benzimidazole) ring attached to side chain of D ring & extra substituent R group

5 Deoxy adenosine

Absorption of B12

Intrinsic protein
Glyco protein (15-20% carbohydrates) MW 50000 Secreted by parietal cells Resistant proteolytic digestion Forms dimer binds to 1 or 2 moles of B12 (1mg IF - 3g B12)

R proteins
Salivary gland & stomach More affinity than that of IF ( 50 folds) in acidic medium Degraded by pancreatic proteins

Transcobalamins I ,II & III

Different genes Immunologically distinct Single peptide 340-375 AA Single binding site Glycoproteins TC II Transport (CH3-B12 & trace HO-B12) TC I &TC III Plasma & Liver storage ( 5 deoxy adenosyl B12)

Bio role as coenzyme

B12 Deficiency

Causes Malnutrition Malabsorption

Congenital failure to secrete IF/HCl Parietal cell destruction/damage Auto immune disease Lack of B12-IF complex receptors Partial/Total gastrectomy Pancreatic disorders/pancreatectomy

Pregnancy Old age

 B12 deficiency symptoms Macrocytic hypochromic Anemia- folate trap Neurological manifestations
Mild paraesthesia Advanced Confusion, Loss of memory, Psychosis

Homocysteinuria / Methylmalonyl aciduria

 B12 deficiency Neurological problems? Methyl malonyl CoA Acts as a competitive inhibitor of malonyl CoA
Substitutes malonyl CoA in fatty acid synthesis Branched FA - Affects membrane integrity

Propionyl CoA Inhibits acetyl CoA carboxylasedefect in FA synthesis in liver,brain etc..

 Cobalamin deficiency assessment

Serum Cobalamin ( ELISA) Schilling test Radio labelled Cobalamin (1G) given orally

Methyl malonic acid in urine Homocysteinuria Peripheral smear Megaloblasts are seen