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VITAMINS
Vitamins may be regarded as organic
compounds required in the diet in small
amounts to perform specific biological
functions for normal maintenance of optimum
growth and health of the organism.
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There are about 15 vitamins, essential for
humans.
They are classified as fat soluble and
water soluble vitamins.
Fat soluble: A, D, E and K
Water soluble: C and B group.
The B complex vitamins may be sub
divided into energy releasing (B1, B2, B6,
biotin etc) and hematopoietic (folic acid
and B12).
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Most of the water soluble vitamins exert
the functions through their respective
coenzymes while only one fat solublevitamins (K) has been identified to function
as a coenzyme.
As far as human are concerned, it isbelieved that the normal intestinal
bacterial synthesis, and absorption of
vitamin K and biotin may be sufficient tomeet the body requirements.
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Administration of antibiotics often kills the
vitamin synthesizing bacteria present in
the gut, hence additional consumption ofvitamins is recommended.
Generally, vitamins deficiencies are
multiple rather than individual withoverlapping symptoms.
The term vitamers represents the
chemically similar substances thatpossess qualitatively similar vitamin
activity.
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Vitamin A
The fat soluble vitamin A, as such ispresent only in foods of animal origin.However, its provitamins carotenes are
found in plants. The term retinoids is often used to include
the natural and synthetic forms of vitaminA.
Retinol, retinal and retinoic acid areregareded as vitamers of vitamin A.
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BIOCHEMICAL FUNCTIONS
Vitamin A is necessary for a variety offunctions such as vision, proper growthand differentiation, reproduction and
maintenance of epithelial cells. Rhodopsin: (mol. Wt. 35,000) is a
conjugated protein present in rods. Itcontain 11-cis retinal and the proteinopsin. The aldehyde group (of retinal) islinked to - amino group of lysine.
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Rods are involved in the dim light visionwhereas cones are responsible for brightlight and color vision.
Dark adaptation time: when a personshifts from a bright light to dim light (e.g.entry into a dim cine theatre), rhodopsin
stores are depleted and vision is impaired.However, within few minutes, known asdark adaptation time, rhodopsin isresynthesized and vision is improved.Dark adaptation time is increased inVitamin A deficient individuals.
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Retinol and retinoic acid function almost
like steroid hormones. They regulate the
protein synthesis and thus involved in thecell growth and differentiaition.
Vitamin A is essential to maintain healthy
epithelial tissue.This is due to the fact thatratinol and retinoic acid are required to
prevent keratin synthesis (responsible for
horny surface) Retinyl phosphate synthesized form
rationol is necessary for the synthesis of
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Certain glycoprotieins which are required for
growth and muscus secretion.
Retinol and retinoic acid are involved in thesynthesis of transferrin, the iron transport
protein.
Vitamin A is considered to be essential for themaintenance of proper immune system to fight
against various infections.
Chelesterol synthesis requires vitamin A.Mevalonate an intermediate in the cholesterol
biosynthesis , is diverted for the
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Synthesis of coenzyme Q in vitamin A
deficiency. It is pertinent to note that the
discovery of coenzyme Q was originallymade in vitamin A deficient animals.
Carotenoids (most important -carotene)
function as antioxidants and reduce the riskof cancers initiated by free radicals and
strong oxidants. carotene is found to be
beneficial to prevent heart attacks. This is
also attributed to the antioxidant property.
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Recommended dietary allowance
The RDA of vitamin A for adults is around1000 retinol equivalents (3500 IU) for manand around 800 retinol equivalents (2500)
for woman. One international unit (IU) equals to 0.3
mg of retinol.
The requirements increases in growingchildern, pregnant woman and lactatingmothers.
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Dietary sources
Animal sources contain preformed vitamin A.The best sources are liver, kidney, egg yolk,milk, cheese, butter.
Fish (cod or shark) liver oils are very rich invitamin A.
Vegetables sources contain the provitamin A-carotenes. Yellow and dark green vegetables
and fruits are good sources of carotenes. E.g.carrots, spinach, amaranthus, pumpkins, mango,papaya etc
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Vitamin A deficiency
The deficiency manifestations are relatedto the eyes, skin and growth.
Deficiency manifestation of the eyes: night
blindness (nyctalopia), is one of theearliest symptoms of vitamin A deficiency.Difficult to see in dim light- as darkadaptation time is increased. Prolongeddeficiency irreversibly damages a numberof visual cells.
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Severe deficiency of vitamin A leads to
xeropthalmia. This is characterized by
dryness in conjuctiva and cornea,keratinization of epithelial cells.
If xeropthalmia persists for a long time,
corneal ulceration and degenerationoccur. This results in the destruction of
cornea, a condition referred to as
keratomalacia, causing total blindness.
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Effect on Growth:
Vitamin A deficiency results in growth
retardation due to imperiment in skeletalformation.
Effect on Reproduction :
The reproductive system is adversely affected in
Vitamin A deficiency. Degeneration of germinal
epithelium leads to sterility in males.
Effect on Skin and epitelial cells :
The skins becomes rough and dry. Keratiniza
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Of epithelial cells of gastrointestinal tract,
urinary tract and respiratory tract is noticed.
This leads to increased bacterial infection.Vitamin A deficiency is associated with
formation of urinary stones. The plasma
level of retinol binding protein is decreasedin Vitamin A deficiency .
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Hypervitaminosis A
Excessive consumption of vitamin A leads
to toxicity.
The symptoms of hypervitaminosis A
include dermatitis (drying and redness of
skin), enlargement of liver, skeletal
decalcification, tenderness of long bones,
loss of weight, irritability, loss of hair, jointpains etc.
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Vitamin D
Vitamin D is a fat soluble vitamin. It
resembles sterol in structure and functions
like a hormone.
Vitamin D was isolated by Angus (1931)
who named it calciferol.
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Chemistry
Ergocalciferol (vitamin D2) is formed from
ergosterol and is present on plants.
Cholecalciferol (vitamin D3) is found in
animals. Both the sterol are similar in
structure except that ergocalciferol has an
additional methyl group and a double
bond.
Ergocalciferol and cholecalciferol are
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Sources for vitamin D activity and are
referred to as provitamins.
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Biochemical functions
Calcitriol (1, 25- DHCC) is the biologically
active form of vitamin D.
It regulates the plasma level of calcium
and phosphate.
Calcitriol acts at 3 different levels
(intestine, kidney and bone) to amintain
plasma calcium level ( normal 9-11 mg/dl)
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Action of calcitriol on the intestine:calcitriol increases the intestinal
absorption of calcium and phosphate. Action of calcitriol on the bone:
Calcitriol stimulates the calcium uptake fordeposition as calcium phosphate. Calcitriolis essential for bone formation.
Action of calcitriol on the kidney:
Calcitriol is also involved in mininmizing
the excretion of calcium and phosphatethrough the kidney by decreasing theirexcretion and enhancing reabsorption.
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Vitamin D is a hormone not a
vitamin- a justification.
Calcitriol is now considered as animportant calcitropic hormone, whilecholecalciferol is the prphormone.
Cholecalciferol (vitamin D3) is synthesizedin the skin by ultra violet rays of sunlight.
The biologically active form of vitamin D,
calcitriol is produced in the kidney. Calcitriol has target organs- intestine boneand kidney, where it specifically acts.
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Calcitrol action action is similar to steroid
hormobnes.
Actinomycin D inhibits the action ofcalcitriol . This support the view that
calcitriol excerts its effect on DNA leadind
to the synthesis of RNA (transcription). Cacitriol synthesis is self regulated by a
feedback mechanism i.e., calcitriol
decreases its own synthesis.
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Recommended dietary Allowance
The daily requirements of vitamin D is 400
international units or 10 mg of
cholecalciferol.
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Dietary sources
Good sources of vitamin d include fatty
fish, fish liver oil, egg yolk etc.
Milk is not a good source of vitamin D.
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Deficiency symptoms
Insufficient exposure to sunlight and
consumption of diet lacking vitamin D results in
its deficiency.
Deficiency of vitamin D causes rickets in childernand osteomalacia in adults.
Vitamin d is often called as antirachitic vitamin.
In rickets plasma calcitriol level is decreased andalkaline phosphatase activity is elevated.
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Renal rickets
This seen in patients with chronic renal
failure.
Renal rickets is mainly due to decreased
synthesis of calcitriol in kidney.
It can be treated by the administration of
calcitriol.
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Hypervitaminosis
Vitamin D is stored mostly in liver and
slowly metabolized.
Vitamin D is the most toxic in overdoses.
Toxic effects- demineralization of bone
(resorption) and increased calcium
absorption from the intestine,
hypercalcemia, loss of appetite, nausea,
increased thirst, loss of weight.
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Vitamin E
Vitamin E (tocopherol) is a naturally
occuring antioxidant.
Essential for normal reproduction in many
animals, hence known as anti sterility
vitamin.
Described as a vitamin in search of a
disease.
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Chemistry
Vitamin E is the name given to a group oftocopherols and tocotrienols.
About eight tocopherols (vitmin E vitamers) havebeen identified , , gama, sigma etc.
- tochopherols is the most active.
The tochopherols are the derivatives of 6-hydroxy chromane (tocol) ring with isoprenoid
(3units) side chain. The antioxidant property is due to chromane
ring.
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Absorption , transport and storage
Vitamin E is absorbed along with fat in the
small intestine. Bile salts are necessary forthe absorption. In the liver, it is incorporated
into lipoproteins (VLDL and LDL) and
transported. Vitamin E is stored in adiposetissue, liver and muscle. The normal plasma
level of tocopherol in less than 1 mg/dl.
Biochemical Functions
Most of the functions of vitamin E are
related to its antioxidant property.
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It prevents the non-enzymatic oxidations of
various cell components (e.g unsaturated
fatty acids) by molecular oxygen and freeradicals such as superoxide (O
2) and
hydrogen peroxide (H2O
2). The element
selenium helps in these function. Vitamin E is lipohilic in character and is
found in association with lipoproteins , fat
deposits and cellular membranes. It protectsthe per oxidation reactions.
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Vitamin E acts as a scavenger and gets itself
oxidized (to quinone form) by free radicals (r)
and spares PUFA.
FUNCTIONS
1) Vitamin E is essential for the membrane
structure and integrity of the cell, hence it is
regarded as a membrane antioxidant.
2) It prevents the peroxidation of poly-
unsaturated fatty acids in various tissues and
membranes.It protects RBC from hemolysisby oxidizing agent (e.g H2O2).
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3) It is closely associated with reproductivefunctions and prevents sterility. VitaminE preserves and maintains germinalepithelium of gonads for properreproductive function.
4) It increases the synthesis of heme by
enhancing the activity of enzymesaninolevulinic acid (ALA) synthase andALA dehydratase.
5) It is required for cellular respirationthrough electron transport chain(believed to stabilize coenzyme Q).
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6) Vitamin E prevents the oxidation ofvitamin A and carotenes.
7) It is required for proper storage ofcreatine in skeletal muscle.
8) Vitamin E is needed for optimalabsorption of amino acids from the
intestine.
9) It is involved in proper synthesis ofnucleic acids.
10)Vitamin E protects liver from beingdamaged by toxic compounds such ascarbon tetrachloride.
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11)It works in association with vitamin A , C
and B carotene, to delay the onset of
cataract.12)Vitamin E has been recommended for
the prevention of chronic diseases such
as cancer and heart diseases.
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VITAMIN K
Vitamin K is the only fat soluble vitamin with a
specific coezyme function. It is required for theproduction of blood clotting factors, essential for
coagulation (in German Koagulation; hence
the name k for this vitamin.
CHEMISTRY
Vitamin K exists in different forms vitamin K1
(Phylloquinone) is present in plants. Vitamin K2
(menaqquinone) is produced by the
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I t ti l b t i d l f d i i l
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Intestinal bacteria and also found in animals.
Vitamin K3 (menadione) is synthetic form.
All the three vitamin (k1,k2,k3) are
naphthoquinone derivatives. Isoprenoid side chain
is present in vitamins K1 and k2. The three
vitamins are stable to heat. Their activity is,
however, lost by oxidizing agents, irradiation,strong acids and alkalies.
Absorption , transport and storage
Vitamin k is taken in the diet or synthesized by the
intestinal bacteria. Its absorption takes place alongwith fat (chylomicrons) and is dependent on bile
S lt Vit i K i t t d l ith
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Salt. Vitamin K is transported along with
LDL and is stored mainly in liver and , to a
lesser extent, in other tissues.Biochemical functions
The functions of vitamin K are concerned
with blood clotting process. It brings aboutthe post-translational (after protein
biosynthesis in the cell) modification of
certain blood clotting factors. The clotting
factors II (prothrombin) VII IX and X are
synthesized as inactive precursors
(zymogens) in the liver. Vitamin K act as a
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Coenzyme for the carboxylation of glutamic
acid residues present in the proteins and
this reaction is catalysed by a carboxylase(microsomal). It involves the conversion of
glutamate (Glu) to carboxyglutamate is
inhibited by dicumarol, an anticoagulantfound in spoilt sweet clover. Warfarin is a
synthetic analogue that can inhibit vitamin K
action.
Vitamin K is also required for the
carboxylation of glutamic acid residues of
O t l i l i bi di t i
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Osteocalcin, a calcium binding protein
present in the bone.
The mechanism of carboxylation is not fullyunderstood. It is known that a 2,3 epoxide
derivative of vitamin K is formed as an
intermediate during the course of the
reation. Dicumarol inhibits the enzymes
(reductase) that converts epoxide to active
Vitamin K.
Role of Gla in clotting
The carboxyglutamic acid (Gla ) residues
Of l tti f t ti l h d
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Of clotting factors are negatively charged
(COO) and they combine with positively
charged calcium ions (Ca2+) to form a
complex. The mechanism of action has
been studied for prothrombin. The
mechanism of action has been studied for
prothrombin. The prothrombin Ca complexbinds to the phospholipids on the
membrane surface of the platelets. This
lead to the increased conversion ofprothrombin to thrombin.
R d d di t ll (RDA)
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Recommended dietary allowance (RDA)
Strictly speaking there is no RDA for vitamin
K, since it can be adequately synthesizedin the gut. It is however , recommended
that half of the body requirement is
provided in the diet, while the other half is
met from the bacterial synthesis.
Accordingly , the suggested RDA for an
adult is 70-140 g/day.
Dietary Sources
Cabbage, cauliflower , tomatoes , alfa alfa,
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Spinach and other green vegetables are
good sources. It also present in egg yolk,
meat, liver, cheese and dairy products.Deficiency symptoms
The deficiency of vitamin K is uncommon ,
since it is present in the diet in sufficientquantity and is adequately synthesized by
the intestinal bacteria. However , vitamin K
deficiency may occur due to its faultyabsorption (lack of bile salts) loss of vitamin
into feces (diarrheal diseases ) and
Ad i i i f ibi i (killi f
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Administration of antibiotics (killing of
intestinal flora).
Deficiency of vitamin k leads to the lack ofactive prothrombin in the circulation. The
result is that blood coagulation is adversely
affected. The individual bleeds profuselyeven for minor injuries .The blood clotting
time is increased.
Hypervitaminsis KAdministration of large doses of vitamin K
produces hemolytic anaemia and jaundice,
P ti l l i i f t Th t i ff t i d
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Particularly in infants. The toxic effect is due
to increased breakdown of RBC.
Antagonists of vitamin kThe compounds namely heparin,
bishydroxycoumarin act as anticoagulants
and are anatagonists to vitamin k. Thesalicylates and dicumarol are also
anatagonists to vitamin K.
Dicumarol is structurally related to vitamin kand acts as a competitive inhibitor in the
synthesis of active prothrombin.
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Vitamin C (Ascorbic acid)
Vitamin C is a water soluble versatile
vitamin.
Scurvy has been known to man for
centuries. It was the first disease found to
be associated with diet.
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chemistry
Ascorbic acid is a hexose derivative andclosely resembles monosaccharides instructure.
The acidic property of Vitamin C is due tothe enolic hydroxyl group. It is a strongreducing agent.
L- ascorbic acid undergoes oxidation toform dehydroascorbic acids and thisreaction is reversible.
B th th f bi l i ll ti
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Both these form are biologically active.
D-Ascorbic acid is inactive.
The plasma and tissues predominantlycontain ascorbic acid in reduced form.
Oxidation of ascorbic acid is rapid in the
presence of copper, hence vitamin Cbecomes inactive if the foods are prepared
in copper vessels.
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Biosynthesis and metabolism.
Many animals can synthesze ascorbicacid from glucose.
Man, other primates guinea pigs and bats
cannot synthesize ascorbic acid due to thedeficiency of a single enzyme namely L-gulonolactone oxidase.
Vitamin C is rapidly absorbed from theintestine. It is not stored in the body to asignificant extent.
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Ascorbic acid is excreted in urine as such
or as its metabolites diketogulonic acid
and oxalic acid.
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Biochemical functions
Most of the function of vitamin C are related to
its property to undergoes reversible oxidation
reduction.
Collagen formation: vitamin C plays the role ofa coenzyme in hydroxylation of proline and
lysine while protocollagen is converted to
collagen. In this way, Vitamin C is necessary for
maintenance of normal connective tissue andwound healing process.
B f ti it i C i i d f b
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Bone formation: vitamin C is required for bone
formation.
Iron and hemoglobin metaboilsm: Ascorbicacid enhances iron absorption by keeping it in
the ferrous form. This is due to reducing property
of Vitamin C. it help in the formation of ferritin
(storage form of iron) and metaboilzation of ironfrom ferritin. Vitamin C is useful in the
reconversion of methemoglobin to hemoglogin.
The degradation of hemoglobin to bile pigments
requires ascorbic acid.
T t h t b li it i C i
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Tryptophan metabolism: vitamin C isessential for the the hydroxylation of
tryptophan to hydroxytryptophan in the thesynthesis of serotonin.
Tyrosine metabolism: ascorbic acid isrequired for the oxidation of p-
hydroxyphenylpyruvate to homogentisicacid in tyrosine metabolism.
Folic acid metabolism: Ascorbic acid is
involve in the formation of the active formof folic acids. Also involved in maturationof erythrocytes.
Peptide hormone synthesis: many
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Peptide hormone synthesis: many
peptide hormone synthesis require vitamin
C. Synthesis of corticosteroid hormones:
vitamin C is necessay for the
hydroxylation reactions in the synthesis of
corticosteroid hormones.
Sparing action of other vitamins:
asorbic acid is a strong antioxidant. It
spares vitamin A, vitamin E and some B-
complex vitamins from oxidation.
I l i l f ti it i C
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Immunological function: vitamin C
enhances the synthesis of
immunoglobulins (antibodies) andincreses the phagocytic action of
leucocytes.
Prevention action on cataract: vitamin Creduces the risk of cataract formation.
Preventive action on chronic diseases:
as an antioxidant, vitamin C reuces therisk of cancer, cataract, and coronary
heart diseases.
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Recommended dietary allowance.
About 60 to 70 mg vitamin C intake per
day will meet the adult requirement.
Additional intakes (20%-40%) are
recommended for women duringpregnancy and lactation.
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Dietary sources
Citrus fruits, gooseberry (amla), guava,
green vegetables (cabbage, spinach)
tomatoes, potatoes (particularly skin) are
rich in ascorbic acid. Milk is poor source of vitamin C.
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Deficiency symptoms
The deficiency of ascorbic acid result in
the Scurvy. This disease is characterized
by spongy and sore gums, loose teeth,
anemia, swollen joints, fragile bloodvessels, decreased immunocompetence,
delayed wound healing, sluggish hormonal
function of adrenal cortex and gonads,haemorrage, osteoporosis etc.
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Thiamine (vitamin B1)
Thiamine (anti- beri beri or antineuritic
vitamin) is a water soluble.
It has a specific coenzyme, thiamine
pyrophosphate (TPP) which is mostlyassociated with carbohydrate metabolism.
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Chemistry
Thiamine contains a pyrimidine ring and a
thiazole ring held by a methylene bridge.
Thiamine is the only natural compound
with thiazole ring.
The alcohol (OH) group of thiamine os
esterified with phosphate (2 moles) to form
the coenzyme, thiamine pyrophosphate(TPP or cocarboxylase).
The pyrophosphate moiety is donated by
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The pyrophosphate moiety is donated by
ATP and the reaction is catalysed by the
enzyme thiamine pyrophosphatetransferase.
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Biochemical function
The coenzyme thiamine pyrophosphate orcocarboxylase is intimately connected withthe energy releasing reactions in the
carbohydrate metabolism. Some of the reactions are dependent onTPP, besides the other coenzyme.
- ketoglutrate dehydrogenase is anenzyme of TCA cycle, this enzyme requireTPP.
Transketolase is dependent on TPP This
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Transketolase is dependent on TPP. This
is an enzyme of hexose monophosphate
shunt (HMP). The branched chain - keto acid
dehydrogenase (decarboxylase) catalyses
the oxidative decarboxylation of branchedchain amino acids (valine, leucine and
isoleucine) to the respective keto acids.
This enzyme also require TPP.
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TPP plays an important role in the
transmission of nerve impulse. It is
believed that TPP is required foracetylcholine synthesis and the ion
translocation of neural tissue.
Recommended diatary allowance (RDA)
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Recommended diatary allowance (RDA)
The daily requirement of thiamine depends
on the intake of carbohydrate. A dietarysupply of 1-1.5 mg/day is recommended foradults (about 0.5 mg/1000 cals of energy).For children RDA is 0.7-1.2 mg/day. The
requirement marginally increases inpregnancy an location (2 mg/day) old rangeand alcoholism.
Dietary Sources
Cereals, pulses, oil seed, nuts and yeast aregood sources. Thiamine is mostlyconcentrated in the outer layer (bran) of
Cereals Polishing of rice removes about
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Cereals. Polishing of rice removes about
80% of thiamine. Vitamin B1 is also
present in animal food like pork, liver,heart, kidney, milk etc. In the parboiled
(boiling of paddy with husk) and milled
rice, thiamine is not lost in polishing , since
thiamine is a water soluble vitamin, It is
extracted into the water during cooking
process. Such water should not be
discarded.
Deficiency symptoms
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y y p
The deficiency of vitamin B1 results in acondition called beri-beri [ sinhalese:1cannot said twice]. Beri beri is mostlyseen in populations consuming exclusivelypolished rice as staple food. The early
symptoms of thiamine deficiency are lossof appetite (anorexia) weekness,constipation , nausea, mental depression,Peripheral neuropathy irritability etc.
Numbness in the legs complaints of pinsand needles sensation are reported.
Biochemical changes in B1 deficiency
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Biochemical changes in B1 deficiency
1. Carbohydrate metabolism is impaired.
Accumulation of pyruvate occurs in thetissues which is harmful. Pyruvate
concentration in plasma is elevated and
it is also excreted in urine.2. Normally, pyruvate does not cross the
blood brain barrier and enter the brain.
However, in thiamine deficiency , an
alteration occurs in the blood brain
permitting the pyruvate to enter the brain
Results in disturbed metabolism that may be
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Results in disturbed metabolism that may be
responsible for polyneuritis.
3. Thiamine deficiency leads to imparimentin nerve impulse transmission due to
lack to TPP.
4. The transketolase activity in erythrocytesis decreased. Measurement of RBC
transketolose activity is a reliable
diagnostic test to assess thiamine
deficiency.
In adults, two types of beri-beri namely
Wet beri beri and dry beri-beri occur. Infantile
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Wet beri beri and dry beri beri occur. Infantile
beri-beri that differs from adult beri-beri is also
seen.
Wet Beri Beri
This is characterized by edema of legs, face,
trunk and serious cavities. Breatless and
palpitation are present. The calf muscles are
slightly swollen. The systolic blood pressure is
elevated while diastolic is decreased. Fast and
bouncing pulse is observed. The heartbecomes weak and death may occur due to
Heart failure
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Heart failure.
Dry beri-beri
This is associated with neuro-logicalmanifestations resulting in peripheral
neutritis. Edema is not commonly seen.
The muscles become progressively weakand walking becomes difficult. The
affected individuals depend on support to
walk and become bedridden and may
even die if not treated.
The symptoms of beri-beri are often mixed
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y p
in which case it is referred to as mixed beri-
beri.
Infantile Beri-Beri
This is seen in infants born to mothers
suffering form thiamine deficiency. Thebreast milk of these mothers contain low
thiamine content. Infantile beri-beri is
characterized by sleeplessness,
restlessness, vomiting , convulsions andbouts of screaming that resemble abdominal
Colic Most of these symptoms are due to
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Colic. Most of these symptoms are due to
cardiac dilatation. Death may occur
suddenly due to cardiac failure.Wernicke Korsakoff syndrome
This is a disorder mostly seen in chronic
alcoholics. The body demands of thiamineincrease in alcoholism. Insufficient intake or
impaired intestinal absorption of thiamine
will lead to this syndrome. It is characterizedby loss of memory, apathy and a rhythmical
to and fromotion of the eye balls.
Thiamine deficiency due to thiaminase and
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y
pyrithiamine
The enzyme thiaminase is present in certain
seafoods. Their inclusion in the diet will destroy
thiamine by a cleavage action (pyrimidine and
thiazole rings are seperated) and lead to
deficiency. Pyrithiamine , a structural analogue andan antimetabolite of thiamine, is found in certain
plants like ferns. Horses and cattle often develop
thiamine deficiency (fern poisoning) due to the
Overconsumption of the plant ferm.
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Overconsumption of the plant ferm.
Thiamine antagonists
Pyrithiamine and oxythiamine are the twoimportant antimetabolites of thiamine.
RIBOFLAVIN (VITAMIN B2)
Riboflavin through its coenzymes takes part in
a variety of cellular oxidation reductionreaction.
Chemistry
Riboflavin contains 6,7 dimethyl isoalloxazine(a hetercyclic 3 ring sturcture)
Attached to D-ribitol by a nitrogen atom. Ribitol
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y g
is an open chain form of sugar ribose with the
aldehyde group (CHO) reduced to alcohol
(CH2OH).
Riboflavin is stable to heat but sensitive to light.
When exposed to ultra-violet rays of sunlight, it
is converted to lumiflavin which exhibits yellowflurescenes. The substances namely lactoflavin
(from milk), hepatoflavin (from liver) and
ovaflavin (from eggs) which were originallythought to be different are
Structurally identical to riboflavin.
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y
Coenzymes of riboflavin
Flavin mononucleotide (FMN) and flavinadenine dinucleotide (FAD) are the twocoenzyme forms of riboflavin. The ribitol (5carbon) is linked to phosphate in FMN.
FAD is formed from FMN by the transfer ofan AMP moiety from ATP.
Biochemical functions
The flavin coenzymes (mostly FAD and to alesser extent FMN) participate in manyredox reactions responsible for energy
Production. The functional unit of both the
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coenzymes is isoalloxazine ring which
serves as an acceptor of two hydrogen
atoms (with electrons). FMN or FAD
undergo identical reversible reactions
accepting two hydrogen atoms forming
FMNNH2or FADH2.
Enzymes that use flavin coenzymes (FMN
or FAD) are called flavoproteins. The
coenzymes (prosthetic groups) often bindrather tightly, to the protein (apoenzyme)
Either by non-covalent bonds (mostly) or
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covalent bonds in the holoenzyme. Many
flavoproteins contain metal atoms (iron,
molybdenum etc). Which are known as
metalloflavoproteins.
The coenzymes FAD and FMN are
associated with certain enzymes involved in
carbohydrate , lipid, protein and purine
metabolism , besides the electron transport
chain. A few examples are listed in Table.
Recommended dietary allowance (RDA)
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Recommended dietary allowance (RDA)
The daily requirement of riboflavin for an
adult is 1.2-1.7 mg. Higher intakes (by 0.2-0.5 mg/day) are advised for pregnant and
lactating women.
Dietary sourcesMilk and milk products, meat, eggs, liver ,
kidney are rich sources. Cereals , fruit,
vegetables and fish are moderate sources.
Deficiency symptoms
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y y p
Riboflavin deficiency symptoms include
cheilosis (fissures at the corners of themouth), glossitis (tongue smooth and
purplish) and dermatitis.Riboflavin
deficiency as such is uncommon. It is mostly
seen along with other vitamin deficiences.
Chronic alcoholics are suscepitible to B2
deficiency. Assay of the enzymes
glutathione reductase in erythrocytes will be
useful in assessing
Riboflavin deficiency.
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Riboflavin deficiency.
Antimetabolite:
Galactoflavin is an antimetabolite ofriboflavin.
NIACIN
Niacin or nicotinic acid is also known aspellagra preventive (P.P) factor of Glodberg.
The coenzymes of niacin (NAD+ and NADP)
can be synthesized by the essential aminoacid tryptophan.
The disease pellagra (Italian rough skin) has
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p g ( g )
been known for certuries. However, its
relation to the deficiency of a dietary factorwas first identified by Goldberger.
Chemistry and synthesis of coenzymes
Niacin is a pyridine derivative. Structurally, itis pyridine 3-carboxylic acid. The amide
form of niacin is known as niacinamide or
nicotinamide.
Dietary nicotinamide niacin and tryptophan
(an essential amino acid) contribute to the
Synthesis of the coenzymes nicotinamide
adenine din cleotide (NAD+) and nicotinamide
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adenine dinucleotide (NAD+)and nicotinamide
adenine dinucleotide phosphate (NADP+). Sixty
milligram of tryptophan is equivalent to 1 mg ofniacin for the synthesis of niacin coenzymes).
Nicotinamide liberated on the degradation of
NAD+ and NADP+ is mostly excreted in urine as
N-methylnicotinamide.
Biochemical FunctionsThe coenzymes NAD+ and NADP+ are involved
in a variety of oxidation -reduction
Reaction. They accept hydride ion
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y p y
(hydrogen atom an one electron H-) and
undergo reduction in the pyridine ring: Thisresults in the neutralization of positive
charges. A large number of enzymes (about
40) belonging to the class oxidoreductases
are dependent on NAD+ and NADP+. NADHproduced is oxidized in the electron
transport chain to generate ATP. NADPH is
also important for many biosyntheticreactions as it donates reducing equivalents.
Recommended dietary allowance (RDA)
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The daily requirement of niacin for an adult
is 15-20 mg and for children around 10-15mg . Very often the term niacin equivalents
(NE) is used while expressing its RDA. One
NE= 1 mg niacin or 60 mg of tryptophan.
Pregnancy an lacatation in women impose
an additional metabolic burden and increase
the niacin requirement.
Dietary Sources
The rich natural sources of niacin include
Liver, yeast, whole grains, cereals, pulses
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, y , g , , p
like beans and peanuts. Milk, fish, egg and
vegetables are moderate sources. Theessential amino acid typtophan can serve as
a precursor for the synthesis of nicotinamide
coenzymes. Tryptophan has many other
essential and important function in the
body , hence dietary tryptophan cannot
totally replace niacin.
Deficiency symptoms
Niacin deficiency results in a condition
Called pellagra (Italian rough skin). This
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disease involves skin , gastrointestinal tract
and central nervous system. The symtomsof pellagra are commonly referred to a three
Ds. The disease also progresses in that
order dermatitis, diarrhea, dementia, and if
not treated may rarely lead to death .
Dermatitis (inflammation of skin) is usually
found in the areas of the skin exposed to
sunlight (neck , dorsal part of feet, ankle
And part of face). Diarrhea may be in the
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form of loose stool, often with blood and
muscus. Prolonged diarrhea leads to weightloss. Dementia is associated with
degeneration of nervous tissues. The
symptoms of dementia , include anxiety ,
irritability , poor memory, insomnia(sleeplessness) etc.
Pellagra is mostly seen among people
whose staple diet is corn or maize. Niacinpresent in maize is unavailable to the body
As it is in bound form. Further , tryptophan contentis low in maize
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is low in maize.
PYRIDOXINE (VITAMIN B6)
VITAMIN B6 is used to collectively represent thethree compounds namely pyridoxine pyridoxal andpyridoxamine (the vitamers of B6).
Chemistry
Vitamin B6 compounds are pyridine derivatives.They differ from each other in the structure of afunctional group attached to 4th carbon in thepyridine ring. Pyridoxine
Is a primary alcohol, pyridoxal is an aldehyde
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from while pyridoxamine is an amine.Pyridoxamine is mostly present in plants while
pyridoxal and pyridoxamine are found in animalfoods. Pyridoxine can be converted topyridoxal and pyridoxamine, but the latter twocannot form pyridoxine.
Synthesis of coenzyme
The active form of vitamin B6 is the coenzymepyridoxal phosphate (PLP). PLP can be
synthesized from the three compoundspyridoxine , pyridoxal and
Pyridoxamine. B6 is excreted in urine as 4-
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pyridoxic acid.
Biochemical functionsPyridoxal phosphate (PLP), the coenzyme of
vitamin B6 is found attached to the E-amino
group of lysine in the enzyme. PLP is closely
associated with the metabolism of amino acids.The synthesis of certain specialized products
such as serotonin, histamine, niacin coenzymes
from amino acids is dependent on pyridoxine.
Pyridoxal phosphate participates in
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reactions like transamination,
decarboxylation, deamination,transsulfuration, condensation.
Pyridoxal phosphate is required for the
synthesis of - amino levulinic acids, the
precursor for the heme synthesis.
The synthesis of niacin coenzymes from
tryptophan is dependent on PLP. The
enzyme kynureninase requires PLP.
PLP plays important role in the
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p y p
metabolism of sulphur containing amino
acids. The enzyme glycogen phosphorylase that
cleaves glycogen to glucose 1-phosphate
contains PLP, covalently bound to lysineresidue.
Adequate intake of B6 is useful to prevent
hyperoxaluria and urinary stone formation.
Recommended dietary allowance
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Recommended dietary allowance
The requirement of pyridoxine for an adultis 2- 2.2mg/day.
During lactation, pregnancy and old age,
an intake of 2.5mg/dl is recommended.
Dietary sources
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Dietary sources
Animal sources such as egg yolk, fish,milk, meat are rich in B6. wheat, corn,
cabbage, roots and tubers are good
vegetables sources.
Deficiency symptoms
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Deficiency symptoms
Pyridoxine deficiency is associated withneurological symtoms such as depression,
irritability, nervousness and mental
confusion. Convulsions and peripheralneuropathy are observed in severe
deficiency. These symptoms are related to
the decreased synthesis of biogenic amines(serotonin, GABA, norepinephrine and
epinephrine). In children B6 deficiency with
A drastically reduced GABA production
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results in convulsions (epilepsy).
Decrease in hemoglobin levels, associatedwith hypochromic microcytic anamia, is seen
in B6 deficiency. This is due to a reduction
in hemo production.
BIOTIN
Biotin (formally known as anti-egg white
injury factor, vitamin B7 or vitamin H) is asulfur containing B-complex vitamin. It
directly participates as a coenzyme in the
Carboxylation reactions.
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Chemistry
Biotin is a hetercyclic sulfur containingmonocarboxylic acid. The structure is
formed by fusion of imidazole and thiophene
rings with a valeric acid side chain. Biotin isconvalently bound to e-amino group of
lysine to form biocytin in the enzymes.
Biocytin may be regarded as the coenzyme
of biotin.
Biochemical functions
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Biotin serves as a carrier of Co2 in carboxylation
reactions. The reaction catalysed by pyruvate
carboxylase, converting pyruvate to oxaloacetate
has been investigated in detail.
1.Glucooneogenesis and citric acid cycle:
The conversion of pyruvate to oxaloacetate thebiotin dependent pyruvate carboxylase
(described above) is essential for the synthesis
of glucose from many
Non-carbohydrate sources. Oxaloacetate so
f d i l i d f th ti
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formed is also required for the continuous
operation of citric acid cycle.
2.Fatty acid synthesis. Acetyl CoA is the
starting material for the synthesis of fatty
acids. The very first step in fatty acid
synthesis is a carboxylation reaction.
BIOTIN
Acetyl coA Malonyl CoA
Acetyl CoA carboxylase
3. Propionyl CoA is produced in the
metabolism of certain amino acids
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metabolism of certain amino acids
(valine, isoleucine, threonine etc.) and
degradation of odd chain fatty acids. Its
further metabolism is dependent on
biotin.
Biotin
Propionyl CoA
Propionyl CoA carboxylase
Recommended dietary allowance (RDA)
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A daily intake of about 100-300 mg is
recommended for adults. In fact, biotin isnormally synthesized by the intestinal
bacteria. However , to what extent the
synthesized biotin contributes to the body
requirements is not clearly known.
Dietary Sources
Biotin is widely distributed in both animal andplant foods. The rich sources are liver ,
kidney , egg yolk, milk, tomatoes grain etc.
Deficiency symptoms
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The symptoms of biotin deficiency include
anemia , loss of appetite, nausea, dermatitis,glossitis etc. Biotin deficiency may also result
in depression , hallucinations, muscle pain
and dermatitis.
PANTOTHENIC ACID
Panthothenic acid (Greek : Pantos-
everywhere) formerly known as chick anti dermatitis factor (or filtrate factor) is widely
distributed in nature. Its metabolic role as
Coenzyme A is also widespread.
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Chemistry and synthesis of coenzyme A
Pantothenic acid consists of two compnents ,pantoic acid and - alanine, held together bya peptide linkage. Synthesis of coenzyme Afrom pantothenate occurs in a series of
reactions.Biochemical Functions
The function of pantothenic acid are exerted
through coenzyme A or CoA ( A foracetylation) . Coenzyme A is a centralmolecule involved in all the metabolism
(carbohydrate, lipid and protien). It play a
i l i i t ti i
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unique role in integrating various
metabolism pathways. More than 70
enzymes that depend on coenzyme A are
known.
Coenzyme A serves as a carrier of activated
acetyl or acyl groups (as thiol esters).This is
comparable with ATP which is a carrier of
activated phosphoryl groups.
A few examples of enzymes involved the
participation of coenzyme are given below.
Pyruvate Acetyl CoA
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Pyruvate dehydrogenase
- Ketoglutarate
- Ketoglutarate dehydrogenase
Fatty Acid Acyl CoA
Thiokinase
Coenzyme A may be regarded as a
coen me of metabolic integration since
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coenzyme of metabolic integration since
acetyl CoA is a central molecule for a wide
variety of biochemical reactions.
Succinyl CoA is also involved in manyreactions including the synthesis of
porphyrins of heme.
Besides the various function through
coenzyme A, pantothenic acid itself is a
component of fatty acid synthase complex
And is involved in the formation of fatty acid.
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Recommended dietary allowance (RDA)
The requirement of pantothenic acid forhumans is not clearly known. A daily intake
of about 5-10 mg is advised for adults.
Dietary sources
Pantothenic acid is one of the most widely
distributed vitamins found in plant and
animals. The rich sources are egg, liver ,meat , yeast , milk etc.
The burning feet syndrome pain and mumbness
in the toes sleeplessness fatigue etc with
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in the toes, sleeplessness, fatigue etc with
pantothenic acid deficiency.
Pantothenic acid deficiency in experimental
animals results in anemia, fatty, liver, decreased
steroid synthesis etc.
Folic AcidFolic acids or folacin Latin folium leaf is
abundantly found in green leafy vegetables. It is
important for one carbon metabolism and isrequired for the synthesis of certain
Amino acid, purines and the pyrimidine thymine.
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Chemistry
Folic acid consists of three components pteridinering , p-amino benzoic acid (PABA) and glutamic
acid (1 to7 residues). Folic acid mostly has one
glutamic acid residues and is known as pteroyl-
glutamic acid (PGA).
The active form of folic acid is tetrahydrofolate
(THF or FH4). It is synthesized from folic acid by
the enzyme
Dihydrofolate reductase. The reducingequivalent are provided by 2 moles of NADPH.
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equivalent are provided by 2 moles of NADPH.The hydrogen atoms are present at positions
5,6,7 and 8 of THF.Biochemical functions
Tetrahydrofolate (THF or FH4) the coenzyme
of folic acid is actively involved in the onecarbon metabolism. THF serves as anacceptor or donor of one carbon units (formly ,methyl etc).in a variety of reaction involving
amino acid and nucleotide metabolism.
Many important compounds are synthesized in
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one carbon metabolism.
1. Purines (carbon 2,8) which are incorporatedinto DNA and RNA.
2.Pyrimidine nucleotide deoxythymidylic acid
(dTMP) involved in the synthesis of DNA.3.Glycine serine ,ethanolamine and choline are
produced.
4.N-formylmethionine, the inititator of proteinbiosynthesis is formed.
Recommended dietary allowance (RDA)
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The daily requirement of folic acid is around
200 g. In the women, higher intakes arerecommended during pregnancy (400 g /day) and loctation (300 g/day).
Dietary sources
Folic acid is widely distributed in nature. Therich sources are green leafy vegetables,whole grains, cereals, liver , kidney, yeast
and eggs. Milk is rather a poor source offolic acid.
Deficiency symptoms
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Folic acid deficiency is probably the most
common vitamin deficiency, observedprimarily in the pregnant women, in both
developed (including USA) and developing
countries (including india). The pregnantwomen, lactating women, women on oral
contraceptives, and alcoholics are also
susceptible to folate deficiency. The folic
acid deficiency may be due to (one or more
causes) inadequate dietary intake, defective
Use of anticonvulsant drugs (phenobarbitone,
)
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dilantin , phenyltoin), and increased demand.
The microcytic anemia (abnormally large RBC)associated with megaloblastic changes in bone
marrow is a characteristic feature of folate
deficiency.
Folic acid and hyperhomocysteinemia
Elevated plasma levels of homocysteine are
associated with increased risk of atherosclerosis,
thrombosis and hypertension.Hyperhomocysteinemia is mostly due to functional
folate deficiency caused by impairment to form
Methyl-tetrahydrofolate reductase. This
results in a failure to convert homocysteine
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results in a failure to convert homocysteine
to methionine. Folic acid supplementationreduces hyperhomocysteinemia, and
thereby the risk for various health
complications.
Folic Acid antagonists
Aminopterin and amethopterin (also called
as methotrexate) are structural analogues of
folic acid. They competitively inhibit
dihydrofolate reductase and block the
Formation of THF. Aminopterin and
th t t f ll d i th
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methotrexate are successfully used in the
treatment of many cancers includingleukemia.
Trimethoprin ( a component of the drug
septran or bactrim) and pyrimethamine
(antimalarial drug) are structurally related to
folic acid. They inhibit dihydrofolate
reductase , and the formation of THF.
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