VITAMINS VITAMINS

BYBYPROF DRPROF DR

NASIR MAHMOOD NASIR MAHMOOD DEPT OF BIOCHEMISTRY DEPT OF BIOCHEMISTRY

VITAMINSVITAMINS

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

CLASSIFICATION CLASSIFICATION

• FAT SOLUBLE VITAMINFAT SOLUBLE VITAMIN

VITAMIN AVITAMIN A

VITAMIN DVITAMIN D

VITAMIN EVITAMIN E

VITAMIN KVITAMIN K• WATER SOLUBLEWATER SOLUBLE

VITAMIN CVITAMIN C

VITAMIN B COMPLEXVITAMIN B COMPLEX

Water Soluble Water Soluble VitaminsVitamins

VIT B COMPLEXVIT B COMPLEX• ENERGY RELEASINGENERGY RELEASING

• VIT B1,B2,B3,BIOTIN,PANTOTHENIC VIT B1,B2,B3,BIOTIN,PANTOTHENIC ACIDACID

• HAEMATOPOETIOCHAEMATOPOETIOC

• FOLIC ACID .VIT B12FOLIC ACID .VIT B12

• OTHERSOTHERS

• VIT B6 VIT B6

WATER SOLUBLE VITAMINSWATER SOLUBLE VITAMINS• NON-TOXICNON-TOXIC• EXCRETED IN URINEEXCRETED IN URINE• NOT STORED EXTENSIVELYNOT STORED EXTENSIVELY• EXCEPT VIT B 12 SO THEIR INTAKE EXCEPT VIT B 12 SO THEIR INTAKE

SHOULD BE MORE FREQUENT.SHOULD BE MORE FREQUENT.

• WATER SOLUBLE VITAMINS WATER SOLUBLE VITAMINS (FEATURES)(FEATURES)

• NOT STORED EXCEPT VIT B12NOT STORED EXCEPT VIT B12

• NO TOXICITY EXCESS EXCRETED IN NO TOXICITY EXCESS EXCRETED IN URINEURINE

• CO-ENZYMES IN METABOLIC CO-ENZYMES IN METABOLIC PROCESSES LIKE CARBOHYDRATE, PROCESSES LIKE CARBOHYDRATE, PROTEIN AND LIPID METABOLISMSPROTEIN AND LIPID METABOLISMS

• RESPIRATORY CHAINRESPIRATORY CHAIN

VITAMIN CVITAMIN C(ASCORBIC ACID)(ASCORBIC ACID)

• SOURCES:-SOURCES:-

VEGETABLES: GREEN CHILLIES AND VEGETABLES: GREEN CHILLIES AND TOMATOESTOMATOES

FRUITS SPECIALLY CITRUS FRUITS, FRUITS SPECIALLY CITRUS FRUITS, GUAVA & STRAWBERRY.GUAVA & STRAWBERRY.

FUNCTIONS OF VITAMIN C FUNCTIONS OF VITAMIN C

• FORMATION OF INTER CELLULAR FORMATION OF INTER CELLULAR GROUND SUBSTANCE INCLUDING GROUND SUBSTANCE INCLUDING COLLAGEN OF FIBROUS COLLAGEN OF FIBROUS TISSUES,MATRICES OF BONES TISSUES,MATRICES OF BONES (CARTILAGES AND DENTINE)(CARTILAGES AND DENTINE)

• CONNECTIVE TISSUES HAVE THE CONNECTIVE TISSUES HAVE THE HIGHEST CONCENTRATION OF VIT C.HIGHEST CONCENTRATION OF VIT C.

• ANTI-OXIDANT ROLE ANTI-OXIDANT ROLE

FUNCTIONFUNCTION

• STEROID SYNTHESISSTEROID SYNTHESIS• ADRENALINE SYNTHESISADRENALINE SYNTHESIS• FOLIC ACID IS CONVERTED TO ITS FOLIC ACID IS CONVERTED TO ITS

ACTIVE FORM TETRAHYDRO-ACTIVE FORM TETRAHYDRO-FOLATE(THF) WITH HELP OF VIT CFOLATE(THF) WITH HELP OF VIT C

• ABSORPTION OF IRON FROM ABSORPTION OF IRON FROM INTESTINE BY REDUCING IN TO INTESTINE BY REDUCING IN TO FERROUS STATEFERROUS STATE

• 60mg PER DAY FOR ADULTS60mg PER DAY FOR ADULTS

CO-ENZYMESAscorbic 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 Mono-oxygenases 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 VIT C DEFICIENCY • SCURVYSCURVY DEFICENT COLLAGN FORMATIONDEFICENT COLLAGN FORMATION FRAGILITY OF VASCULAR WALL CAUSING FRAGILITY OF VASCULAR WALL CAUSING

BLEEDING TENDENCY, MUSCLE WEAKNESS, BLEEDING TENDENCY, MUSCLE WEAKNESS, SOFT SWOLLEN BLEEDING GUMS.SOFT SWOLLEN BLEEDING GUMS.

POOR WOUND HEALINGPOOR WOUND HEALING DEFICENCY OF BONE MATRIX CAUSING DEFICENCY OF BONE MATRIX CAUSING

POOR HEALING OF FRACTUREPOOR HEALING OF FRACTURE ANAEMIAANAEMIA

ScurvyScurvy• Bleeding gumsBleeding gums• easy bruisingeasy bruising• impaired wound healing and impaired wound healing and

bone repairbone repair• joint painjoint pain

PREVENTIONPREVENTION• DIET SHOULD CONTAIN CITRUS FRUITS AND FRESH DIET SHOULD CONTAIN CITRUS FRUITS AND FRESH

VEGETABLESVEGETABLES• INFANT SHOULD BE FED ON MOTHER’S MILK I.E INFANT SHOULD BE FED ON MOTHER’S MILK I.E

BREAST FEEDING & GIVEN JUICEBREAST FEEDING & GIVEN JUICE• DIFFERENT FRUITS HAVE FOLLOWING CONCENT DIFFERENT FRUITS HAVE FOLLOWING CONCENT

RATIONS OF VIT C. RATIONS OF VIT C. • LEMON 50 mg/gLEMON 50 mg/g• ORANGE 49 mg/gORANGE 49 mg/gBLOOD LEVEL OF VIT C IS 1 mg/dlBLOOD LEVEL OF VIT C IS 1 mg/dl• LESS THAN 0.4 mg/dl DEFICIENCY OCCURLESS THAN 0.4 mg/dl DEFICIENCY OCCUR• LESS THAN 0.2 mg/dl SCURVY APPEARSLESS THAN 0.2 mg/dl SCURVY APPEARS• NORMAL STORES OF VIT-C ARE SUFFICIENT FOR 3-4 NORMAL STORES OF VIT-C ARE SUFFICIENT FOR 3-4

MONTHS BEFORE SCURVY APPEARSMONTHS BEFORE SCURVY APPEARS

VIT C TOXICITYVIT C TOXICITY

• NO ACUTE TOXICITY HAS BEEN OBSERVEDNO ACUTE TOXICITY HAS BEEN OBSERVED

VITAMIN B-1 (THIAMINE)VITAMIN B-1 (THIAMINE)

SOURCES:-SOURCES:-• UNREFINED CEREALS, MEAT, NUTS, UNREFINED CEREALS, MEAT, NUTS,

GREEN VEGETABLES, EGGS.GREEN VEGETABLES, EGGS.

ACTIVATIONACTIVATION ACTIVE THIAMINE IS THIAMINE ACTIVE THIAMINE IS THIAMINE

DIPHOSPHATE OR THIAMINE DIPHOSPHATE OR THIAMINE PYRROPHOSPHATE(TDP/TPP)PYRROPHOSPHATE(TDP/TPP)

ACTIVATION OCCURS IN BRAIN & ACTIVATION OCCURS IN BRAIN & LIVERLIVER

FUNCTIONSFUNCTIONS

• NORMAL FUNCTIONS OF NERVOUS NORMAL FUNCTIONS OF NERVOUS SYSTEMSYSTEM

• MAINLY FOR CARBIHYDRATE MAINLY FOR CARBIHYDRATE METABOLISMMETABOLISM

• ACTS AS CO-ENZYME FOR ACTS AS CO-ENZYME FOR REACTIONS OF CITRIC ACID CYCLE REACTIONS OF CITRIC ACID CYCLE SO PLAYS KEY ROLE IN ENERGY SO PLAYS KEY ROLE IN ENERGY METABOLISMMETABOLISM

CO-ENZYMESTHIAMINE PYROPOSPHATE:

Co-enzyme for oxidative decarboxylation for ketoacids

Pyruvate Acetyl CoA

Pyruvate +TPP Acetalaldehyde -TPP complex+Co2

Alpha ketogluterate+6 CoA-SH Succinyl CoA + Co2

Ribose-5 Po4 + Xylulose-5-Po4 Sedoheptulose 7-Po4

+ 3 phosphoglyceraldehyde

Pyruvate dehydrogenase

Pyruvate decarboxylase

-ketogluteratedehydrogenase

Transketolase

CoA NAD NADH-H+

NAD NADH-H+

DEFECIENCYDEFECIENCY• THE OVER ALL PICTURE OF SEVERE THIAMINE THE OVER ALL PICTURE OF SEVERE THIAMINE

DEFICENCY INCLUDE NEUROLOGICAL DEFICENCY INCLUDE NEUROLOGICAL CARDIOVASCULAR AND G.I.T DISORDER WHICH CARDIOVASCULAR AND G.I.T DISORDER WHICH IS REFER AS IS REFER AS BERI BERIBERI BERI

• TYPES OF BERI BERI TYPES OF BERI BERI • DRY BERI BERIDRY BERI BERI• WET BERI BERIWET BERI BERI• CEREBAL BERI BERICEREBAL BERI BERI• INFANTILE BERI BERIINFANTILE BERI BERI

Infantile Beri-BeriInfantile Beri-Beri

• first 6 monthsfirst 6 months

• breast milk deficient in B-1breast milk deficient in B-1

• rapid onsetrapid onset

• cyanosis, tachycardia, labored cyanosis, tachycardia, labored breathingbreathing

• heart failure and deathheart failure and death

Wet Beri BeriWet Beri Beri• Symptoms similar to Symptoms similar to

congestive heart failurecongestive heart failure

• Pitting edema - trunk, limbs, Pitting edema - trunk, limbs, faceface

• Labored breathing, Labored breathing, tachycardiatachycardia

• Rapid deteriorationRapid deterioration

• Fatal circulatory collapseFatal circulatory collapse

• Responds rapidly to B-1 Responds rapidly to B-1 supplementssupplements

DRY BERI BERI(PERIPHERAL DRY BERI BERI(PERIPHERAL NEUTITIS)NEUTITIS)

• LONG STANDING DEFICIENCY OF VIT BLONG STANDING DEFICIENCY OF VIT B11

• DEGENERATION AND DEMYELINATION OF DEGENERATION AND DEMYELINATION OF SENSORY AND MOTOR NERVESSENSORY AND MOTOR NERVES

• MUSCLE WASTING, CALF MUSCLEMUSCLE WASTING, CALF MUSCLE• REFLEXES ARE LOW (KNEE JERK)REFLEXES ARE LOW (KNEE JERK)

Dry Beri-BeriDry Beri-Beri

• No edemaNo edema• Progressive wastingProgressive wasting• Numbness and Numbness and

weakness of extremitiesweakness of extremities• Chronic infectionsChronic infections

WERNICK’S ENCAPHALOPATHYWERNICK’S ENCAPHALOPATHY• OCCURS IN ALCOHALICS WITH OCCURS IN ALCOHALICS WITH

DEFICIENCY OF VIT BDEFICIENCY OF VIT B11 IN DIET. PURELY IN DIET. PURELY

INVOLVE CEREBRAL CORTEXINVOLVE CEREBRAL CORTEX

• CLINICAL FEATURESCLINICAL FEATURES [IN ALCOHALICS, DIET DEF IN B[IN ALCOHALICS, DIET DEF IN B11]]

• CONFUSION,, CONFUSION,,

• ATAXIA(SHAKY MOVEMENT), DROWSINESSATAXIA(SHAKY MOVEMENT), DROWSINESS

• INTELLIGENCE DISTURBANCEINTELLIGENCE DISTURBANCE

• DOUBLE VISION,NYSTAGMUS.DOUBLE VISION,NYSTAGMUS.

• TRANSKETOLASE ACTIVITY IS LOWTRANSKETOLASE ACTIVITY IS LOW

KORSAKOFF’S PSYCHOSISKORSAKOFF’S PSYCHOSIS• UNTREATED WERNICK’S UNTREATED WERNICK’S

ENCAPHALOPATHY LEADS TO ENCAPHALOPATHY LEADS TO PERMANENT DAMAGE OF THE BRAINPERMANENT DAMAGE OF THE BRAIN

• PROFOUND IMPAIRMENT OF PROFOUND IMPAIRMENT OF MEMORY, OTHERWISE CONSCOIUSMEMORY, OTHERWISE CONSCOIUS

• INDIVIDUAL INCAPABLE OF LIVING INDIVIDUAL INCAPABLE OF LIVING INDEPENDENTLYINDEPENDENTLY

• REQUIRES INSTITUTIONAL CAREREQUIRES INSTITUTIONAL CARE

RIBOFLAVIN (VIT BRIBOFLAVIN (VIT B22))

1.1. SOURCES:SOURCES: YEAST, LIVER, KIDNEY, MILK. YEAST, LIVER, KIDNEY, MILK. YELLOW FLORESCENT PIGMENT. DECOMPOSES YELLOW FLORESCENT PIGMENT. DECOMPOSES IN LIGHT.IN LIGHT.

2.2. BIOCHEMICAL ROLEBIOCHEMICAL ROLE

ACTIVE FORM IS FLAVIN MONONUCLEOTIDE ACTIVE FORM IS FLAVIN MONONUCLEOTIDE (FMN) AND FLAVIN ADENINE- DI- NUCLEOTIDE (FMN) AND FLAVIN ADENINE- DI- NUCLEOTIDE (FAD). THESE ARE CALLED FLAVO PROTEINS (FAD). THESE ARE CALLED FLAVO PROTEINS [CONTAIN IRON][CONTAIN IRON]

FLAVIN + ATPFLAVIN + ATP FMN + ATP FMN + ATP FADFAD• SERVES AS CO-ENZYME OF OXIDATION-SERVES AS CO-ENZYME OF OXIDATION-

REDUCTION REACTIONS.REDUCTION REACTIONS.

BIOCHEMICAL ROLEBIOCHEMICAL ROLEREDUCTION OF FAD OR FMN TO FADH2

OR FMNH2

FMN is co enzyme for Cytochrome C Oxidase, L.Amino acid Dehydrogenase

FAD is co-enzyme for Xanthene Oxidase Acyl-CoA Dehydrogenase

• REDUCED FORMS OF FMN AND FAD REDUCED FORMS OF FMN AND FAD TAKE PART IN SYNTHESIS OF ATPs TAKE PART IN SYNTHESIS OF ATPs THROUGH OXIDATIVE THROUGH OXIDATIVE PHOSPHORLATION.PHOSPHORLATION.

DEFICIENCYDEFICIENCY

1.1.ANGULAR STOMATITISANGULAR STOMATITIS• NOT SPECIFIC. RESULT DUE TO COMBINED NOT SPECIFIC. RESULT DUE TO COMBINED

DEFICIENCY OF NIACIN, PYRIDOXIN & IRON. IT DEFICIENCY OF NIACIN, PYRIDOXIN & IRON. IT CAN FOLLOW HERPES FIBRILIS AT THE CAN FOLLOW HERPES FIBRILIS AT THE ANGLES OF MOUTH.ANGLES OF MOUTH.

• 2.CHEILOSIS 2.CHEILOSIS ISIS ZONE OF RED ZONE OF RED EPITHELIUM AT THE LINE OF EPITHELIUM AT THE LINE OF CLOSURE OF CLOSURE OF LIPS. COMBINED LIPS. COMBINED WITH WITH NIACIN I.E. ALSO SEEN IN NIACIN I.E. ALSO SEEN IN PELLAGRA ( DEF. OF NIACIN )PELLAGRA ( DEF. OF NIACIN )

3.3. SCALINESS AND GREASINESS IN SCALINESS AND GREASINESS IN THE THE FOLDS OF NOSE AND EAR.FOLDS OF NOSE AND EAR.

4.4. VASCULARIZATOIN OF CORNEA, VASCULARIZATOIN OF CORNEA, PHOTOPHOPIA, ITCHINGPHOTOPHOPIA, ITCHING

5.5. ANAEMIAANAEMIA6.6. DERAMATITIS OF SCROTUM AND DERAMATITIS OF SCROTUM AND

VULVA.VULVA.• DEFICIENCY IN EXPERIMENTAL DEFICIENCY IN EXPERIMENTAL

ANIMALS INDUCES BIRTH DEFECTS ANIMALS INDUCES BIRTH DEFECTS DURING PREGNANCYDURING PREGNANCY

RIBOFLAVIN (VIT B2)RIBOFLAVIN (VIT B2)

• DEFICIENCYDEFICIENCY

• ARIBOFLAVINOSISARIBOFLAVINOSIS INFLAMATION OF MOUTHINFLAMATION OF MOUTH INFLAMATION OF TONGUEINFLAMATION OF TONGUE FISSURES AT THE ANGLE OF THE FISSURES AT THE ANGLE OF THE

MOUTHMOUTH DERMATITISDERMATITISVASCULARIZATION OF CORNEAVASCULARIZATION OF CORNEA

NIACIN (VIT- B-3)NIACIN (VIT- B-3)• SOURCES:SOURCES: WIDELY DISTRIBUTED PLANTS WIDELY DISTRIBUTED PLANTS

AND ANIMALS, COFFEE GOOD SOURCE, LIVER, AND ANIMALS, COFFEE GOOD SOURCE, LIVER, MEAT, FISHMEAT, FISH

• TRYPTOPHAN (60 mg) CONVERTED TO VIT BTRYPTOPHAN (60 mg) CONVERTED TO VIT B66 (1mg)(1mg)

• RESISTANT TO HEAT. RESISTANT TO HEAT. • NIACIN, NICOTINAMIDE AND NICOTINIC ACIDNIACIN, NICOTINAMIDE AND NICOTINIC ACID

BIOCHEMICAL ROLEBIOCHEMICAL ROLE• ACTIVE NIACIN IS NICOTINAMIDE ADENINE DI-ACTIVE NIACIN IS NICOTINAMIDE ADENINE DI-

NUCLEOTIDE (NAD) AND NICOTINAMIDE NUCLEOTIDE (NAD) AND NICOTINAMIDE ADENINE DI-NUCLEOTIDE PHOSPHATE (NADP)ADENINE DI-NUCLEOTIDE PHOSPHATE (NADP)

• NAD AND NADP ARE CO-ENZYMES OF ENZYMES NAD AND NADP ARE CO-ENZYMES OF ENZYMES OXIDOREDUCTASESOXIDOREDUCTASES..

Chemical Characteristics of Chemical Characteristics of Niacin B3Niacin B3

• relatively stable torelatively stable to– lightlight– heatheat– oxidationoxidation– alkalialkali

1.1. THEY ARE KEY COMPONENTS OF THEY ARE KEY COMPONENTS OF METABOLIC PATHWAYS FOR METABOLIC PATHWAYS FOR CARBOHYDRATES, LIPIDS AND AMINO CARBOHYDRATES, LIPIDS AND AMINO ACID METABOLISM (TCA, HMP)ACID METABOLISM (TCA, HMP)

2.2. CO-ENZYME FOR DEHYDROGENASES CO-ENZYME FOR DEHYDROGENASES ENZYMESENZYMES

3. LACTATE DEHYROGENASE IN 3. LACTATE DEHYROGENASE IN CYTOSOLCYTOSOL

4. MALATE DEHYDROGENASE IN 4. MALATE DEHYDROGENASE IN MITOCHONDRIAMITOCHONDRIA

5. PART OF RESPIRATORY CHAIN 5. PART OF RESPIRATORY CHAIN

NIACIN (VIT B3)NIACIN (VIT B3)

• DEFICIENCYDEFICIENCY

• PELLAGRAPELLAGRA

THIS DESEASE INVOLVE:-THIS DESEASE INVOLVE:- SKINSKIN G.I.TG.I.T CNSCNS

PELLAGRAPELLAGRA CHARACTERIZED BY THREE D’SCHARACTERIZED BY THREE D’S DERMATITISDERMATITIS DIARRHOEADIARRHOEA DEMENTIA AND IF NOT TREATED DEMENTIA AND IF NOT TREATED

DEATHDEATH

Assessment of B-3 StatusAssessment of B-3 Status• Urinary excretion of Niacin metabolitesUrinary excretion of Niacin metabolites

BIOTIN

• Part of multiunit enzymes causing carboxylation reactions. Acts as carrier of CO2

Acetyl CoA+HCo3 + ATP Malonyl-CoA

Pyruvate+ HCo3 + ATP Oxaloacetate+ ADP+Pi

NH4 + HCo3 + 2ATP CarbamoylPO4 + 2 ADP+ 2 Pi

Synthesis of Purines and Pyrimidines

AcetylcarboxylaseEnz-Biotin-COO- Enz-Biotin

Pyruvate carboxylase .Biotin

Carbamoyl Po4.Synthetase - Biotin

BIOTINBIOTIN

• DEFICIENCYDEFICIENCY

• NAUSEANAUSEA

• DEPRESSIONDEPRESSION

• SLEEPINESSSLEEPINESS

• ALOPECIAALOPECIA

• DERMATITISDERMATITIS

FOLIC ACIDFOLIC ACID

• SOURCESSOURCES

GREEN LEAFY VEGETABLES, GREEN LEAFY VEGETABLES, LIVER, YEASTLIVER, YEAST

DAILY REQUIREMENTS IS 200 DAILY REQUIREMENTS IS 200 MICRO GRAMS. INCREASED MICRO GRAMS. INCREASED DURING PREGNANCY AND DURING PREGNANCY AND LACTATIONLACTATION

BIOCHEMICAL ROLEBIOCHEMICAL ROLEACTIVE FORM IS TETRAHYDOFOLATE (H(H44

FOLATE)FOLATE)FORMED BYFORMED BY FOLATE REDUCTASE AND ACTS AS SINGLE CARBON CARRIER FOR SYNTHESIS OF VARIOUS COMPOUNDS LIKE PYRIMIDINES & PURINES { E.G CONVERSION OF dUMP (DEOXYURIDYLATE) INTO dTMP (DEOXYTHYMIDYLATE)}

• THF RECIEVES ONE –CARBON FRAGMENTS THF RECIEVES ONE –CARBON FRAGMENTS FROM DONORS SUCH AS SERINE,GLYCINE FROM DONORS SUCH AS SERINE,GLYCINE AND HISTIDINE AND TRASFERS THEM TO AND HISTIDINE AND TRASFERS THEM TO SPECIFIC INTERMEDIATES IN THE SPECIFIC INTERMEDIATES IN THE SYNTHESIS OF AMINO ACIDS, PURINES AND SYNTHESIS OF AMINO ACIDS, PURINES AND PYRIMIDINES(THYMINE)PYRIMIDINES(THYMINE)

FOLIC ACIDFOLIC ACID• METHOTREXATE, ANALOG OF 1O-

METHYLE-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 B12 (CYANOCOBALAMIN) WHICH ALSO MAINTAINS FOLATE IN ITS ACTIVE FORM I.E. THF.

• DEFICIENCY OF B12 LEADS TO “FOLATE TRAP”: OCCOMULATION OF FOLATE IN ITS INACTIVE THEREFORE NON USEABLE FORM

FOLATEFOLATE DEFICIENCYDEFICIENCY

• MEGALOBLASTIC ANAEMIAMEGALOBLASTIC ANAEMIADECREASE DNA SYNTHESISDECREASE DNA SYNTHESISNORMAL PROTEIN SYNTHESISNORMAL PROTEIN SYNTHESISLARGE IMMATURE RBCs I.E. LARGE IMMATURE RBCs I.E.

MEGALOBLAST ARE FORMED MEGALOBLAST ARE FORMED INSTEAD OF NORMOBLAST IN INSTEAD OF NORMOBLAST IN BONE MARROW & BLOODBONE MARROW & BLOOD

Folate and Neural Tube DefectsFolate and Neural Tube Defects• Defects in formation of neural Defects in formation of neural

tube (Brain & Spinal Cord) usually tube (Brain & Spinal Cord) usually occurring during first two months occurring during first two months of gestation (pregnancy)of gestation (pregnancy)

• Anencephaly: Absence of Anencephaly: Absence of cerebral hemispherescerebral hemispheres

• Folate Supplementation before Folate Supplementation before conception & during 1st trimester conception & during 1st trimester of pregnancy reduces this riskof pregnancy reduces this risk

Folate and Neural Tube DefectsFolate and Neural Tube Defects

• Spina-bifidaSpina-bifida–Defective closure of vertebral columnDefective closure of vertebral column–Spinal cord protrusion from spinal Spinal cord protrusion from spinal

column results in damage to spinal column results in damage to spinal cordcord

–Lower limb and hip paralysisLower limb and hip paralysis–Rectal and bladder problemsRectal and bladder problems

COBALAMIN (VIT B12)COBALAMIN (VIT B12)

SOURCES:-SOURCES:-

ANIMAL SOURCES INCLUDE MEAT, ANIMAL SOURCES INCLUDE MEAT, LIVER, EGG, MILK, FISH, POULTRYLIVER, EGG, MILK, FISH, POULTRY

ABSENT IN PLANT FOODABSENT IN PLANT FOOD

SOME AMOUNT MAY BE FORMED BY SOME AMOUNT MAY BE FORMED BY COLONIC BACTERIACOLONIC BACTERIA

COBALAMINES (VIT BCOBALAMINES (VIT B1212))

VITAMIN B12 :EXTRINSIC FACTORVITAMIN B12 :EXTRINSIC FACTOR REQUIRED FOR THREE ESSENTIAL REQUIRED FOR THREE ESSENTIAL

ENZYMATIC REACTIONSENZYMATIC REACTIONS SYNTHESIS OF METHEONINE FROM SYNTHESIS OF METHEONINE FROM

HOMOCYSEINEHOMOCYSEINE ISOMERIZATION OF METHYL-MALONYL CO-AISOMERIZATION OF METHYL-MALONYL CO-A CONVERSION OF FOLIC ACID TO ITS ACTIVE CONVERSION OF FOLIC ACID TO ITS ACTIVE

FORM THFFORM THF

RDA = 3 MICROGRAM/DAYRDA = 3 MICROGRAM/DAY

ABSORPTION, TRANSPORT AND STORAGEABSORPTION, TRANSPORT AND STORAGE• INTRINSIC FACTOR (IF) MANDATORY FOR INTRINSIC FACTOR (IF) MANDATORY FOR

ABSORPTION, STORED IN LIVER ABSORPTION, STORED IN LIVER

VITAMIN B12VITAMIN B12

• VIT B12 IS THE ONLY WATER SOLUBLE VIT B12 IS THE ONLY WATER SOLUBLE VIT THAT IS STORED IN SGNIFICANT VIT THAT IS STORED IN SGNIFICANT AMOUNTS IN THE LIVER, BONE AMOUNTS IN THE LIVER, BONE MARROW AND OTHER TISSUESMARROW AND OTHER TISSUES

• INTRINSIC FACTOR IS REQUIRED FOR INTRINSIC FACTOR IS REQUIRED FOR ITS ABSORPTIONITS ABSORPTION

DIGESTION & ABSORPTION OF BDIGESTION & ABSORPTION OF B1212

• INTRINSIC FACTORINTRINSIC FACTOR• Gastric glycoproteinGastric glycoprotein

• Binds with BBinds with B1212 in small intestine in small intestine

• IF-BIF-B1212 complex binds to B complex binds to B1212receptor in ileum receptor in ileum

for absorptionfor absorption

• BB1212 absorption requires functioning absorption requires functioning

stomach, pancreas, and ileumstomach, pancreas, and ileum• In absence of IF Vitamin B12 is not In absence of IF Vitamin B12 is not

absorbedabsorbed

VITAMIN B12• FUNCTIONS/BIOCHEMICAL ROLES

Acts as co-enzyme in groups rearrangements in Isomerases e.g.

conversion of Methyl Malonyl CoA into Succinyl-CoA by enzyme

Methylmalonyl-CoA MutaseConverts Homocystein into Methionine

Act as maturation factor for RBCs

DEFICIENCYDEFICIENCY(PERNICIOUS ANEMIA)(PERNICIOUS ANEMIA)

CAUSES: CAUSES: • DIETARY (VEGANS)DIETARY (VEGANS)• INTRINSIC FACTOR DEFICIENCYINTRINSIC FACTOR DEFICIENCY

GASTRIC ATROPHYGASTRIC ATROPHYCONGENITAL DEFICIENCYCONGENITAL DEFICIENCYTOTAL GASTRECTOMYTOTAL GASTRECTOMY

• DISEASE OF TERMINAL ILLEUMDISEASE OF TERMINAL ILLEUM• DRUGSDRUGS

B-12 DeficiencyB-12 Deficiency• Pernicious anemiaPernicious anemia• Megaloblastic AnemiaMegaloblastic Anemia

–Delayed or failure of normal cell Delayed or failure of normal cell division/maturation due to division/maturation due to impaired DNA synthesisimpaired DNA synthesis

• NeuropathyNeuropathy – Defective MyelinationDefective Myelination– Progressive Peripheral Muscular Progressive Peripheral Muscular

WeakeningWeakening– Unresponsive to Folate TherapyUnresponsive to Folate Therapy

• NEUROLOGICAL PROBLEMSNEUROLOGICAL PROBLEMSo PARAESTHESIA OF FINGER AND PARAESTHESIA OF FINGER AND

TOESTOES

o DEMENTIA MAY OCCURDEMENTIA MAY OCCUR

o UNSTEADINESS OF GAITUNSTEADINESS OF GAIT

o SPINAL CORD AND PERIPHERAL SPINAL CORD AND PERIPHERAL NERVES ARE INVOLVEDNERVES ARE INVOLVED

DEFICIENCYDEFICIENCY• MEGALOBLASTIC ANAEMIAMEGALOBLASTIC ANAEMIA• SUBACUTE COMBINED SUBACUTE COMBINED

DEGENERATION (SCD)DEGENERATION (SCD) OF OF SPINALCORDSPINALCORD AFFECTING AFFECTING PERIPHERAL NERVESPERIPHERAL NERVES DUE DUE OCCUMULATION OF ABNORMAL OCCUMULATION OF ABNORMAL FATTY ACIDS WHICH ALSO FATTY ACIDS WHICH ALSO AFFECTS AFFECTS NORMAL NORMAL MYELINATIONMYELINATION OF NERVES OF NERVES

LABORATORY DIAGNOSISLABORATORY DIAGNOSIS::• LEVEL IN RBCs, SHAPE OF RBCs LEVEL IN RBCs, SHAPE OF RBCs

(MEGALOBLASTIC)(MEGALOBLASTIC)

• DECREASED SERUM VIT BDECREASED SERUM VIT B1212

• SCHILLING TEST: DECREASED SCHILLING TEST: DECREASED ABSORPTION OF LABELLED B12ABSORPTION OF LABELLED B12

• PRESENCE OF ANTIBODY TO PRESENCE OF ANTIBODY TO INTRINSIC FACTORINTRINSIC FACTOR

PYRIDOXAL PHOSPHATE(B6)• SIX COMPOUNDS HAVE B6 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(B6)

• DIETARY SOURCES:• PLANT SOURCES: YEAST, RICE

POLISHING, SEEDS , CEREAL GRAINS

• ANIMAL SOURCES: EGG YOLK

• MILK IS A POOR SOURCE

PYRIDOXAL PHOSPHATE(B6)

• FUNCTIONS:

• COENZYME FOR AMINO ACID METABOLISM I.E.TRANSAMINATION & DECARBOXYLATION, GLYCOGEN METABOLISM GLYCOGEN PHOSPHORYLASE.

• ALSO INVOLVED IN TERMINATION OF STEROID HORMONE ACTION, LOW B6 LEADS TO PROLONGED ACTION OF THESE HORMONES.

VITAMIN B6 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

Aspartate transaminase (AST)

Glutamic acid + PLP(B6) ketoglutaric

acid + Oxalo acetic acid Aspartic acid

Alanine transaminase (ALT)

Glutamic acid + PLP(B6) ketoglutaric

acid + Pyruvic acid Alanine

PYRIDOXAL PHOSPHATE(B6)

• DEFICIENCY:DEFICIENCY:• NO SEPARATE DEFICIENCY KNOWN OR NO SEPARATE DEFICIENCY KNOWN OR

DESCRIBED DESCRIBED • A PECULAR A PECULAR “NEURITIS”“NEURITIS” OR EVEN OR EVEN

“NEUROPATHY”“NEUROPATHY” CAN DEVELOP AFTER CAN DEVELOP AFTER DEFICIENCY SYNDROME DUE TO INTAKE DEFICIENCY SYNDROME DUE TO INTAKE OF AN ANTI-TUBERCULOSIS DRUG OF AN ANTI-TUBERCULOSIS DRUG “ISONIAZID”“ISONIAZID”

• TRYPTOPHAN METBOLISMTRYPTOPHAN METBOLISM ALSO ALSO DISTURBED LEADING TO EXCRETION OF DISTURBED LEADING TO EXCRETION OF XANTHURENIC ACID IN URINEXANTHURENIC ACID IN URINE