Transcript File

VITAMINS
BY
PROF DR
NASIR MAHMOOD
DEPT OF BIOCHEMISTRY
VITAMINS
• VITAMINS ARE ORGANIC
COMPOUNDS REQUIRED BY BODY IN
SMALL AMOUNTS TO PERFORM/
REGULATE SPECIFIC CELLULAR
FUNCTIONS.
CLASSIFICATION
• FAT SOLUBLE VITAMIN
VITAMIN A
VITAMIN D
VITAMIN E
VITAMIN K
• WATER SOLUBLE
VITAMIN C
VITAMIN B COMPLEX
Water Soluble
Vitamins
VIT B COMPLEX
• ENERGY RELEASING
• VIT B1,B2,B3,BIOTIN,PANTOTHENIC
ACID
• HAEMATOPOETIOC
• FOLIC ACID .VIT B12
• OTHERS
• VIT B6
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 B12
• 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
• 60mg 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 7hydroxylcholesterol
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
 DEFICENT COLLAGN FORMATION
 FRAGILITY OF VASCULAR WALL CAUSING
BLEEDING TENDENCY, MUSCLE WEAKNESS,
SOFT SWOLLEN BLEEDING GUMS.
 POOR WOUND HEALING
 DEFICENCY OF BONE MATRIX CAUSING
POOR HEALING OF FRACTURE
 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
CoA
Pyruvate
NAD
NADH-H+
Pyruvate dehydrogenase
Acetyl CoA
Pyruvate +TPP Pyruvate decarboxylase
Acetalaldehyde TPP
-ketogluteratedehydrogenase
complex+Co2
NAD
Alpha ketogluterate+6 CoA-SH
Succinyl
Transketolase
CoA + Co2
Ribose-5 Po4 + Xylulose-5-Po4
NADH-H+
Sedoheptulose
DEFECIENCY
• THE OVER ALL PICTURE OF SEVERE
THIAMINE DEFICENCY INCLUDE
NEUROLOGICAL CARDIOVASCULAR
AND G.I.T DISORDER WHICH IS REFER
AS BERI BERI
• TYPES OF BERI BERI
• DRY BERI BERI
• WET BERI BERI
• CEREBAL BERI 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 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 BERI(PERIPHERAL
NEUTITIS)
• LONG STANDING DEFICIENCY OF VIT B1
• 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 B1 IN DIET. PURELY
INVOLVE CEREBRAL CORTEX
• CLINICAL FEATURES
•
•
•
•
•
[IN ALCOHALICS, DIET DEF IN B1]
CONFUSION,,
ATAXIA(SHAKY MOVEMENT), DROWSINESS
INTELLIGENCE DISTURBANCE
DOUBLE VISION,NYSTAGMUS.
TRANSKETOLASE ACTIVITY IS LOW
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 B2)
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 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
TAKE PART IN SYNTHESIS OF ATPs
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 B2)
• DEFICIENCY
• ARIBOFLAVINOSIS
 INFLAMATION OF MOUTH
INFLAMATION OF TONGUE
 FISSURES AT THE ANGLE OF THE
MOUTH
 DERMATITIS
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 B6
(1mg)
• 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 B3
• 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 B3)
• DEFICIENCY
• PELLAGRA
THIS DESEASE INVOLVE: SKIN
 G.I.T
 CNS
PELLAGRA
CHARACTERIZED BY THREE
D’S
 DERMATITIS
 DIARRHOEA
 DEMENTIA AND IF NOT
TREATED DEATH
BIOTIN
• Part of multiunit enzymes causing carboxylation
reactions. Acts as carrier of CO2
Acetylcarboxylase
Acetyl CoA+HCo3 + ATP Enz-Biotin-COO-  EnzCoA
Biotin
Pyruvate carboxylase .Biotin
Malonyl-
Pyruvate+ HCo3 + ATP
Oxaloacetate+
Carbamoyl Po .Synthetase ADP+Pi
4
Biotin
NH4 + HCo3 + 2ATP
CarbamoylPO4
+ 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
(H4
FOLATE)FORMED 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
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 1OMETHYLE-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
FOLATE DEFICIENCY
• MEGALOBLASTIC ANAEMIA
DECREASE DNA SYNTHESIS
NORMAL PROTEIN SYNTHESIS
LARGE 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 1st trimester
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 B12)
SOURCES:ANIMAL SOURCES INCLUDE MEAT,
LIVER, EGG, MILK, FISH,
POULTRY
ABSENT IN PLANT FOOD
SOME AMOUNT MAY BE FORMED
BY COLONIC BACTERIA
COBALAMINES (VIT B12)
 VITAMIN B12 :EXTRINSIC FACTOR
 REQUIRED FOR THREE ESSENTIAL
ENZYMATIC REACTIONS



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 B12
• VIT B12 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
B12
INTRINSIC FACTOR
Gastric glycoprotein
Binds with B12 in small intestine
IF-B12 complex binds to B12receptor in
ileum for absorption
• B12 absorption requires functioning
stomach, pancreas, and ileum
• In absence of IF Vitamin B12 is not
absorbed
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 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
• Pernicious
B-12anemia
Deficiency
• 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
LABORATORY DIAGNOSIS:
• LEVEL IN RBCs, SHAPE OF RBCs
(MEGALOBLASTIC)
• DECREASED SERUM VIT B12
• SCHILLING TEST: DECREASED
ABSORPTION OF LABELLED B12
• PRESENCE OF ANTIBODY TO
INTRINSIC 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
Glutamic acid +
Aspartate
transaminase (AST)
PLP(B6)
Oxalo acetic acid
Glutamic acid +
Pyruvic acid
Alanine
transaminase (ALT)
PLP(B6)

ketoglutaric acid +
Aspartic acid

ketoglutaric acid +
Alanine
PYRIDOXAL PHOSPHATE(B6)
• 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