VITAMINS VITAMINS ARE ORGANIC COMPOUNDS REQUIRED BY BODY

VITAMINS • VITAMINS ARE ORGANIC COMPOUNDS REQUIRED BY BODY IN SMALL AMOUNTS TO PERFORM/ REGULATE SPECIFIC CELLULAR FUNCTIONS.

CLASSIFICATION • FAT SOLUBLE VITAMIN A VITAMIN D VITAMIN E VITAMIN K • WATER SOLUBLE VITAMIN C VITAMIN B COMPLEX

Water Soluble Vitamins

VIT B COMPLEX • ENERGY RELEASING • VIT B 1, B 2, B 3, BIOTIN, PANTOTHENIC ACID • HAEMATOPOETIOC • FOLIC ACID. VIT B 12 • OTHERS • VIT B 6

WATER SOLUBLE VITAMINS • • NON-TOXIC EXCRETED IN URINE NOT STORED EXTENSIVELY EXCEPT VIT B 12 SO THEIR INTAKE SHOULD BE MORE FREQUENT.

• WATER SOLUBLE VITAMINS (FEATURES) • NOT STORED EXCEPT VIT B 12 • NO TOXICITY EXCESS EXCRETED IN URINE • CO-ENZYMES IN METABOLIC PROCESSES LIKE CARBOHYDRATE, PROTEIN AND LIPID METABOLISMS • RESPIRATORY CHAIN

VITAMIN C (ASCORBIC ACID) • SOURCES: VEGETABLES: GREEN CHILLIES AND TOMATOES FRUITS SPECIALLY CITRUS FRUITS, GUAVA & STRAWBERRY.

FUNCTIONS OF VITAMIN C • FORMATION OF INTER CELLULAR GROUND SUBSTANCE INCLUDING COLLAGEN OF FIBROUS TISSUES, MATRICES OF BONES (CARTILAGES AND DENTINE) • CONNECTIVE TISSUES HAVE THE HIGHEST CONCENTRATION OF VIT C. • ANTI-OXIDANT ROLE

FUNCTION • • • STEROID SYNTHESIS ADRENALINE SYNTHESIS FOLIC ACID IS CONVERTED TO ITS ACTIVE FORM TETRAHYDROFOLATE(THF) WITH HELP OF VIT C • ABSORPTION OF IRON FROM INTESTINE BY REDUCING IN TO FERROUS STATE • 60 mg PER DAY FOR ADULTS

CO-ENZYMES Ascorbic acid (Vitamin C) • Strong reducing agent • Required for hydroxylation of proline into hydroxyproline for synthesis of collagen – Conversion of tyrosine into dopamine and into catecholamines (adrenaline and noradrenalin) – Bile acid formation – Conversion of cholesterol into 7 hydroxylcholesterol

VITAMIN C (ASCORBIC ACID) Maintain metallic co-factors like Cu+ in Monooxygenases and Fe in Di-oxygenases in reduced form Conversion of cholesterol into steroid hormone in adrenal cortex Absorption of iron by reducing into reduced form which is can be easily absorbed Acts as antioxidant in GIT by preventing formation of nitrosamines during digestion

VIT C DEFICIENCY • SCURVY Ø DEFICENT COLLAGN FORMATION Ø FRAGILITY OF VASCULAR WALL CAUSING BLEEDING TENDENCY, MUSCLE WEAKNESS, SOFT SWOLLEN BLEEDING GUMS. Ø POOR WOUND HEALING Ø DEFICENCY OF BONE MATRIX CAUSING POOR HEALING OF FRACTURE Ø ANAEMIA

Scurvy • • • Bleeding gums easy bruising impaired wound healing and bone repair • joint pain

PREVENTION • DIET SHOULD CONTAIN CITRUS FRUITS AND FRESH VEGETABLES • INFANT SHOULD BE FED ON MOTHER’S MILK I. E BREAST FEEDING & GIVEN JUICE • DIFFERENT FRUITS HAVE FOLLOWING CONCENT RATIONS OF VIT C. • LEMON 50 mg/g • ORANGE 49 mg/g BLOOD LEVEL OF VIT C IS 1 mg/dl • LESS THAN 0. 4 mg/dl DEFICIENCY OCCUR • LESS THAN 0. 2 mg/dl SCURVY APPEARS • NORMAL STORES OF VIT-C ARE SUFFICIENT FOR 3 -4 MONTHS BEFORE SCURVY APPEARS

VIT C TOXICITY • NO ACUTE TOXICITY HAS BEEN OBSERVED

VITAMIN B-1 (THIAMINE) SOURCES: • UNREFINED CEREALS, MEAT, NUTS, GREEN VEGETABLES, EGGS. ACTIVATION § ACTIVE THIAMINE IS THIAMINE DIPHOSPHATE OR THIAMINE PYRROPHOSPHATE(TDP/TPP) § ACTIVATION OCCURS IN BRAIN & LIVER

FUNCTIONS • NORMAL FUNCTIONS OF NERVOUS SYSTEM • MAINLY FOR CARBIHYDRATE METABOLISM • ACTS AS CO-ENZYME FOR REACTIONS OF CITRIC ACID CYCLE SO PLAYS KEY ROLE IN ENERGY METABOLISM

CO-ENZYMES THIAMINE PYROPOSPHATE: Co-enzyme for oxidative decarboxylation for ketoacids Co. A Pyruvate NADH-H+ Pyruvate dehydrogenase Acetyl Co. A Pyruvate +TPP Pyruvate decarboxylase Acetalaldehyde TPP -ketogluteratedehydrogenase complex+Co 2 NAD Alpha ketogluterate+6 Co. A-SH Succinyl Transketolase Co. A + Co 2 Ribose-5 Po 4 + Xylulose-5 -Po 4 NADH-H+ Sedoheptulose 7

DEFECIENCY • THE OVER ALL PICTURE OF SEVERE THIAMINE DEFICENCY INCLUDE NEUROLOGICAL CARDIOVASCULAR AND G. I. T DISORDER WHICH IS REFER AS BERI • TYPES OF BERI • DRY BERI • WET BERI • CEREBAL BERI • INFANTILE BERI

Infantile Beri-Beri • • first 6 months breast milk deficient in B-1 rapid onset cyanosis, tachycardia, labored breathing • heart failure and death

Wet Beri • Symptoms similar to congestive heart failure • Pitting edema - trunk, limbs, face • Labored breathing, tachycardia • Rapid deterioration • Fatal circulatory collapse • Responds rapidly to B-1 supplements

DRY BERI(PERIPHERAL NEUTITIS) • LONG STANDING DEFICIENCY OF VIT B 1 • DEGENERATION AND DEMYELINATION OF SENSORY AND MOTOR NERVES • MUSCLE WASTING, CALF MUSCLE • REFLEXES ARE LOW (KNEE JERK)

Dry Beri-Beri • No edema • Progressive wasting • Numbness and weakness of extremities • Chronic infections

WERNICK’S ENCAPHALOPATHY • OCCURS IN ALCOHALICS WITH DEFICIENCY OF VIT B 1 IN DIET. PURELY INVOLVE CEREBRAL CORTEX • CLINICAL FEATURES • • [IN ALCOHALICS, DIET DEF IN B 1] CONFUSION, , ATAXIA(SHAKY MOVEMENT), DROWSINESS INTELLIGENCE DISTURBANCE DOUBLE VISION, NYSTAGMUS.

KORSAKOFF’S PSYCHOSIS • UNTREATED WERNICK’S ENCAPHALOPATHY LEADS TO PERMANENT DAMAGE OF THE BRAIN • PROFOUND IMPAIRMENT OF MEMORY, OTHERWISE CONSCOIUS • INDIVIDUAL INCAPABLE OF LIVING INDEPENDENTLY • REQUIRES INSTITUTIONAL CARE

RIBOFLAVIN (VIT B 2) 1. SOURCES: YEAST, LIVER, KIDNEY, MILK. YELLOW FLORESCENT PIGMENT. DECOMPOSES IN LIGHT. 2. BIOCHEMICAL ROLE ACTIVE FORM IS FLAVIN MONONUCLEOTIDE (FMN) AND FLAVIN ADENINE- DI- NUCLEOTIDE (FAD). THESE ARE CALLED FLAVO PROTEINS [CONTAIN IRON] FLAVIN + ATP FMN + ATP FAD • SERVES AS CO-ENZYME OF OXIDATIONREDUCTION REACTIONS.

BIOCHEMICAL ROLE REDUCTION OF FAD OR FMN TO FADH 2 OR FMNH 2 FMN is co enzyme for Cytochrome C Oxidase, L. Amino acid Dehydrogenase FAD is co-enzyme for Xanthene Oxidase Acyl-Co. A Dehydrogenase • REDUCED FORMS OF FMN AND FAD TAKE PART IN SYNTHESIS OF ATPs THROUGH OXIDATIVE PHOSPHORLATION.

DEFICIENCY 1. ANGULAR STOMATITIS • NOT SPECIFIC. RESULT DUE TO COMBINED DEFICIENCY OF NIACIN, PYRIDOXIN & IRON. IT CAN FOLLOW HERPES FIBRILIS AT THE ANGLES OF MOUTH. • 2. CHEILOSIS IS ZONE OF RED EPITHELIUM AT THE LINE OF CLOSURE OF LIPS. COMBINED WITH NIACIN I. E. ALSO SEEN IN PELLAGRA ( DEF. OF NIACIN )

SCALINESS AND GREASINESS IN THE FOLDS OF NOSE AND EAR. 4. VASCULARIZATOIN OF CORNEA, PHOTOPHOPIA, ITCHING 3. 5. ANAEMIA 6. DERAMATITIS OF SCROTUM AND VULVA. • DEFICIENCY IN EXPERIMENTAL ANIMALS INDUCES BIRTH DEFECTS DURING PREGNANCY

RIBOFLAVIN (VIT B 2) • DEFICIENCY • ARIBOFLAVINOSIS Ø INFLAMATION OF MOUTH Ø INFLAMATION OF TONGUE Ø FISSURES AT THE ANGLE OF THE MOUTH Ø DERMATITIS Ø VASCULARIZATION OF CORNEA

NIACIN (VIT- B-3) • SOURCES: WIDELY DISTRIBUTED PLANTS AND ANIMALS, COFFEE GOOD SOURCE, LIVER, MEAT, FISH • TRYPTOPHAN (60 mg) CONVERTED TO VIT B 6 (1 mg) • RESISTANT TO HEAT. • NIACIN, NICOTINAMIDE AND NICOTINIC ACID BIOCHEMICAL ROLE • ACTIVE NIACIN IS NICOTINAMIDE ADENINE DINUCLEOTIDE (NAD) AND NICOTINAMIDE ADENINE DI-NUCLEOTIDE PHOSPHATE (NADP) • NAD AND NADP ARE CO-ENZYMES OF ENZYMES OXIDOREDUCTASES.

Chemical Characteristics of Niacin B 3 • relatively stable to – light – heat – oxidation – alkali

1. THEY ARE KEY COMPONENTS OF METABOLIC PATHWAYS FOR CARBOHYDRATES, LIPIDS AND AMINO ACID METABOLISM (TCA, HMP) 2. CO-ENZYME FOR DEHYDROGENASES ENZYMES 3. LACTATE DEHYROGENASE IN CYTOSOL 4. MALATE DEHYDROGENASE IN MITOCHONDRIA 5. PART OF RESPIRATORY CHAIN

NIACIN (VIT B 3) • DEFICIENCY • PELLAGRA THIS DESEASE INVOLVE: Ø SKIN Ø G. I. T Ø CNS

PELLAGRA CHARACTERIZED BY THREE D’S Ø DERMATITIS Ø DIARRHOEA Ø DEMENTIA AND IF NOT TREATED DEATH ØAssessment of B-3 Status • Urinary excretion of Niacin

BIOTIN • Part of multiunit enzymes causing carboxylation reactions. Acts as carrier of CO 2 Acetyl Co. A+HCo 3 + ATP Co. A Acetylcarboxylase Enz-Biotin-COO- Enz-Biotin Malonyl- Pyruvate carboxylase. Biotin Pyruvate+ HCo 3 + ATP Oxaloacetate+ Carbamoyl Po. Synthetase ADP+Pi - Biotin 4 NH 4 + HCo 3 + 2 ATP Carbamoyl. PO 4 + 2 ADP+ 2 Pi

BIOTIN • • • DEFICIENCY NAUSEA DEPRESSION SLEEPINESS ALOPECIA DERMATITIS

FOLIC ACID • SOURCES GREEN LEAFY VEGETABLES, LIVER, YEAST DAILY REQUIREMENTS IS 200 MICRO GRAMS. INCREASED DURING PREGNANCY AND LACTATION

BIOCHEMICAL ROLE ACTIVE FORM IS TETRAHYDOFOLATE (H 4 FOLATE)FORMED BY FOLATE REDUCTASE AND ACTS AS SINGLE CARBON CARRIER FOR SYNTHESIS OF VARIOUS COMPOUNDS LIKE PYRIMIDINES & PURINES { E. G CONVERSION OF d. UMP (DEOXYURIDYLATE) INTO d. TMP (DEOXYTHYMIDYLATE)} • THF RECIEVES ONE –CARBON FRAGMENTS FROM DONORS SUCH AS SERINE, GLYCINE AND HISTIDINE AND TRASFERS THEM TO SPECIFIC INTERMEDIATES IN THE SYNTHESIS OF AMINO ACIDS, PURINES AND PYRIMIDINES(THYMINE)

FOLIC ACID • METHOTREXATE, ANALOG OF 1 OMETHYLE-TETRAHYDROFOLATE INHIBITS FOLATE REDUCTASE THEREFORE USED AS ANTI CANCER DRUG • INHIBITOR OF BACTERIAL/PARASITIC FOLATE REDUCTASE LIKE TRIMETHOPRIM/PYRIMTHAMINE USEDAS ANTIBACTERIAL/ ANTIMALARIAL DRUGS

FOLIC ACID(THF) • ACTS AS MATURATION FACTOR FOR GROWTH OF RAPIDLY DIVIDING CELLS LIKE RBCs IN COMBINATION OF ANOTHER ESSENTIAL MATURATION FACTOR I. E VITAMIN B 12 (CYANOCOBALAMIN) WHICH ALSO MAINTAINS FOLATE IN ITS ACTIVE FORM I. E. THF. • DEFICIENCY OF B 12 LEADS TO “FOLATE TRAP”: OCCOMULATION OF FOLATE IN ITS INACTIVE THEREFORE NON USEABLE FORM

FOLATE DEFICIENCY • MEGALOBLASTIC ANAEMIA ØDECREASE DNA SYNTHESIS ØNORMAL PROTEIN SYNTHESIS ØLARGE IMMATURE RBCs I. E. MEGALOBLAST ARE FORMED INSTEAD OF NORMOBLAST IN BONE MARROW & BLOOD

Folate and Neural Tube Defects • Defects in formation of neural tube (Brain & Spinal Cord) usually occurring during first two months of gestation (pregnancy) • Anencephaly: Absence of cerebral hemispheres • Folate Supplementation before conception & during 1 st trimester of pregnancy reduces this risk

Folate and Neural Tube Defects • Spina-bifida – Defective closure of vertebral column – Spinal cord protrusion from spinal column results in damage to spinal cord – Lower limb and hip paralysis – Rectal and bladder problems

COBALAMIN (VIT B 12) SOURCES: ANIMAL SOURCES INCLUDE MEAT, LIVER, EGG, MILK, FISH, POULTRY ABSENT IN PLANT FOOD SOME AMOUNT MAY BE FORMED BY COLONIC BACTERIA

COBALAMINES (VIT B 12) Ø VITAMIN B 12 : EXTRINSIC FACTOR Ø REQUIRED FOR THREE ESSENTIAL ENZYMATIC REACTIONS Ø Ø Ø SYNTHESIS OF METHEONINE FROM HOMOCYSEINE ISOMERIZATION OF METHYL-MALONYL CO-A CONVERSION OF FOLIC ACID TO ITS ACTIVE FORM THF RDA = 3 MICROGRAM/DAY ABSORPTION, TRANSPORT AND STORAGE • INTRINSIC FACTOR (IF) MANDATORY FOR ABSORPTION, STORED IN LIVER

VITAMIN B 12 • VIT B 12 IS THE ONLY WATER SOLUBLE VIT THAT IS STORED IN SGNIFICANT AMOUNTS IN THE LIVER, BONE MARROW AND OTHER TISSUES • INTRINSIC FACTOR IS REQUIRED FOR ITS ABSORPTION

DIGESTION & ABSORPTION OF B 12 • • INTRINSIC FACTOR Gastric glycoprotein Binds with B 12 in small intestine IF-B 12 complex binds to B 12 receptor in ileum for absorption • B 12 absorption requires functioning stomach, pancreas, and ileum • In absence of IF Vitamin B 12 is not absorbed

VITAMIN B 12 • FUNCTIONS/BIOCHEMICAL ROLES Acts as co-enzyme in groups rearrangements in Isomerases e. g. conversion of Methyl Malonyl Co. A into Succinyl-Co. A by enzyme Methylmalonyl-Co. A Mutase Converts Homocystein into Methionine Act as maturation factor for RBCs

DEFICIENCY (PERNICIOUS ANEMIA) CAUSES: • DIETARY (VEGANS) • INTRINSIC FACTOR DEFICIENCY GASTRIC ATROPHY CONGENITAL DEFICIENCY TOTAL GASTRECTOMY • DISEASE OF TERMINAL ILLEUM • DRUGS

B-12 Deficiency • Pernicious anemia • Megaloblastic Anemia –Delayed or failure of normal cell division/maturation due to impaired DNA synthesis • Neuropathy – Defective Myelination – Progressive Peripheral Muscular Weakening – Unresponsive to Folate Therapy

• NEUROLOGICAL PROBLEMS o PARAESTHESIA OF FINGER AND TOES o DEMENTIA MAY OCCUR o UNSTEADINESS OF GAIT o SPINAL CORD AND PERIPHERAL NERVES ARE INVOLVED

DEFICIENCY • MEGALOBLASTIC ANAEMIA • SUBACUTE COMBINED DEGENERATION (SCD) OF SPINALCORD AFFECTING PERIPHERAL NERVES DUE OCCUMULATION OF ABNORMAL FATTY ACIDS WHICH ALSO AFFECTS NORMAL MYELINATION OF

LABORATORY DIAGNOSIS: • LEVEL IN RBCs, SHAPE OF RBCs (MEGALOBLASTIC) • DECREASED SERUM VIT B 12 • SCHILLING TEST: DECREASED ABSORPTION OF LABELLED B 12 • PRESENCE OF ANTIBODY TO INTRINSIC FACTOR

PYRIDOXAL PHOSPHATE(B 6) • SIX COMPOUNDS HAVE B 6 ACTIVITY: PYRIDOXINE, PYRIDOXAL, PYRIDOXAMINE & THEIR 5’PHOSPHATES • ACTIVE COENZYME IS PYRIDOXAL PHOSPHATE • 80% PRESENT IN MUSCLES ASSOCIATED WITH GLYCOGEN PHOSPHORYLASE ENZYME • INVOLVED IN GLUCONEOGENESIS FROM AMINO ACIDS

PYRIDOXAL PHOSPHATE(B 6) • DIETARY SOURCES: • PLANT SOURCES: YEAST, RICE POLISHING, SEEDS , CEREAL GRAINS • ANIMAL SOURCES: EGG YOLK • MILK IS A POOR SOURCE

PYRIDOXAL PHOSPHATE(B 6) • FUNCTIONS: • COENZYME FOR AMINO ACID METABOLISM I. E. TRANSAMINATION & DECARBOXYLATION, GLYCOGEN METABOLISM GLYCOGEN PHOSPHORYLASE. • ALSO INVOLVED IN TERMINATION OF STEROID HORMONE ACTION, LOW B 6 LEADS TO PROLONGED ACTION OF THESE HORMONES.

VITAMIN B 6 BIOCHEMICAL ROLE Transaminases. Catalyzing transfer of amino group between an amino acid and a ketoacid e. g. Aspartate transaminase (AST), Alanine transaminase (ALT) with coenzyme Pyridoxal Phosphate Glutamic acid + Aspartate transaminase (AST) PLP(B 6) Oxalo acetic acid Glutamic acid + Pyruvic acid Alanine transaminase (ALT) PLP(B 6) ketoglutaric acid + Aspartic acid ketoglutaric acid + Alanine

PYRIDOXAL PHOSPHATE(B 6) • DEFICIENCY: • NO SEPARATE DEFICIENCY KNOWN OR DESCRIBED • A PECULAR “NEURITIS” OR EVEN “NEUROPATHY” CAN DEVELOP AFTER DEFICIENCY SYNDROME DUE TO INTAKE OF AN ANTI-TUBERCULOSIS DRUG “ISONIAZID” • TRYPTOPHAN METBOLISM ALSO DISTURBED LEADING TO EXCRETION OF XANTHURENIC ACID IN URINE