VITAMINS

Learning Objectives

Define, classify vitamins and enumerate the difference

between fat soluble and water soluble vitamins

Describe the metabolism, biochemical functions,

deficiency diseases associated with inadequate intake,
and toxicity of excessive intakes of the vitamins
 Definition and classification of vitamins

 Vitamins are organic nutrients that are required in small

quantities for a variety of biochemical functions and
which generally cannot be synthesized by the body and
must, therefore, be supplied by the diet.

 Some vitamins can be synthesized by intestinal

microorganisms, but in quantities that are not sufficient to
meet our needs.
Classification of vitamins

1. Water soluble vitamins

2. Fat soluble vitamins

 Water soluble vitamins

 Vitamin B complex, e.g.

– Thiamine (vitamin B1)
– Riboflavin (vitamin B2)
– Niacin (vitamin B3)
– Pantothenic acid (vitamin B5)
– Pyridoxine (vitamin B6)
– Biotin
– Folic acid
– Cobalamin (vitamin B12)
 Vitamin C or ascorbic acid.
Fat soluble vitamins

– Vitamin A or retinol

– Vitamin D or cholecalciferol

– Vitamin E or tocopherol

– Vitamin K.
 Fat Soluble Vs. Water Soluble Vitamins

Fat soluble vitamins Water soluble vitamins

Function as coenzymes, Function as precursor for
hormones and coenzymes and
antioxidants antioxidants
Toxic when taken in Usually non-toxic
excessive quantities
Can be stored Not stored extensively
except vitamin B12,
 Thiamine (Vitamin B1)

Thiamine consists of a pyrimidine ring attached to a thiazole

ring by methylene bridge.

Structure of thiamin.
Active Form of Thiamine

Thiamine pyrophosphate (TPP) is an active coenzyme

form of vitamin thiamine
Sources

 It is present in all natural foods but particularly good

dietary sources are unrefined cereals, meat, nuts, green
vegetables, eggs, etc.

 White bread and polished rice are very poor sources of

the vitamin thiamine.
Functions

 Thiamine is required mainly for carbohydrate

metabolism

 Thiamine pyrophosphate (TPP) is a coenzyme involved

in oxidative decarboxylation and transketolase
reactions .
1. Oxidative Decarboxylation

 TPP is a coenzyme for pyruvate dehydrogenase complex

which catalyzes the conversion of pyru- vate into acetyl
CoA.

 Acetyl-CoA is a precursor for the synthesis of

neurotransmitter acetylcholine and also for the synthesis
of myelin. Thus, thiamine is required for the normal
functioning of the nervous system.
2. TPP is a coenzyme for α-ketoglutarate dehydro- genase
which catalyzes the conversion of α-ketoglutarate to
succinyl-CoA in TCA cycle

3. TPP is a coenzyme for the enzyme transketolase, in the

pentose phosphate pathway of glucose oxidation

Nutritional Requirements

Nutritional Research Council recommends daily intake

of 1.0 to 1.5 mg of thiamine for adults which is increased
with increased muscular activity, dietary carbohydrates
and in pregnancy and lactation.
Deficiency Manifestations

 The deficiency of vitamin B1 results in a condition called

beriberi.

 Deficiency of thiamine occurs in population who consume

exclusively polished rice as staple food.

 The early symptoms of thiamine deficiency are anorexia

(lack of appetite) , nausea, mental confusion, peripheral
neuritis, and muscle fatigue.
Beriberi

Beriberi is divided into three types, relating to the body

system involved i.e. Nervous or cardiovascular or age of
patient (infantile).

1. Dry beriberi (neuritic beriberi): affects the nervous system

2. Wet beriberi (cardiac beriberi): affects cardiovascular system

3. Infantile beriberi: affects children of malnourished mothers.

Dry beriberi (neuritic beriberi)

It develops when the diet chronically contains slightly less

than requirements. It is characterized by:

–Vomiting.

–Poor appetite

–Peripheral neuritis

–Difficulty in walking

–Tingling or loss of sensation, numbness in hands

and feet
–Severe muscular weakness and fatigue.

–Mental confusion/speech difficulties

–Dry skin

–Involuntary eye movements (nystagmus)

Wet beriberi (cardiac beriberi)

 It develops when the deficiency is more severe in which

cardiovascular system is affected in addition to
neurological symptoms.

 Wet beriberi is characterized by:

− Peripheral Edema (swelling of lower legs)

−Heart enlargement and cardiac insuffi- ciency.

−Increased heart rate tachycardia

−It is sometimes fatal

Infantile beriberi

 Infantile beriberi is observed in breast fed infants

(between two and six months of age) whose
mothers have inadequate thiamine intake. The
breast milk of these mothers is deficient in
thiamine.
 It is characterized by

−GI disturbances such as vomiting ,diarrhea

− Cardiac dilation (enlargement of heart),

−Tachycardia (rapid heart rate)

− Convulsions,

−Edema

−In acute condition, the infant may die due to

cardiac failure.
Wernicke-Korsakoff Syndrome

 Wernicke-Korsakoff Syndrome (WKS) is a neurological

disorder caused by a deficiency of vitamin thiamine
(vitamin B1) due to chronic alcohol consumption

 It is also known as cerebral beriberi.

 In chronic alcoholics, the nutritional deficiencies result

from either poor intake of food or malabsorp- tion of
nutrients from intestine.
Symptoms

 Mental confusion and impaired short-term memory.

 Impaired person’s ability to learn new information or tasks.

 Ataxia (Loss of muscle coordination that can cause weakness

in limbs and leg tremor)

 Paralysis of eye muscles

 Nystagmus (Abnormal eye movements back & forth

movements of eye)

 Double vision, eyelid drooping

Antimetabolites

Thiamine can be destroyed if the diet contains thiaminase.

Thiaminase is present in raw fish and seafood.

Thiamine Assay

Whole blood or Erythrocyte transketolase (requiring TPP

as a coenzyme) activity is used as a measure of thiamine
deficiency.
 Riboflavin (Vitamin B2)

Riboflavin is a yellow compound (Flavus = yellow in

Latin) consisting of a isoalloxazine ring with a ribitol

(sugar alcohol) side chain

Active Form of Riboflavin

 Flavin mononucleotide (FMN)

 Flavin adenine dinucleotide (FAD)

Structure of riboflavin and its active coenzyme forms FMN and
FAD.
Sources

 The main dietary sources of riboflavin are yeast,

germinating seeds, green leafy vegetables milk and milk

products, eggs, liver , meat etc.

 Cereals are a poor source

Nutritional Requirements

 The RDA for vitamin B2 is 1.3 to 1.7 mg for adults.

 It is related to protein use and increases during growth,

pregnancy, lactation and wound healing.

Functions
 Riboflavin is a precursor of coenzymes FMN and FAD, which
are required by several oxidation-reduction reactions in
metabolism.
 FMN and FAD serve as coenzymes for oxidoreductase
enzymes involved in carbohydrate, protein, lipid, nucleic acid
metabolism and electron transport chain.
 Decarboxylation of pyruvate and α-ketoglutarate requires FAD
 Fatty acyl CoA dehydrogenase requires FAD in fatty acid
oxidation
 Synthesis of active form of folate (5-methyl THF) requires
FADH2

 FAD is required to convert tryptophan to niacin (vit B3)

 Reduction of the oxidized form of glutathione (GSSG) to

its reduced form (GSH) is also FAD dependent. Thus they
are also involved in detoxification reactions

 It is needed for maintenance of mucosal epithelial &

ocular tissues.
 Deficiency Manifestations

Riboflavin deficiency (ariboflavinosis) is quite

rare. It is most commonly seen in chronic

alcoholics.
The characteristic symptoms of riboflavin deficiency are:

 Cheilosis: Cracks at the angles of the mouth,

 Glossitis: Inflammation of the tongue that becomes

swollen and magenta colored

 Dermatitis: Rough and scaly skin

 Vascularization (the development of blood vessels)

of cornea. The eyes become red, itchy, watery and
sensitive to bright light.
 Niacin (Vitamin B3)
Structure

Niacin is a general name for the nicotinic acid and

nicotinamide, either of which may act as a source of the
vitamin in the diet. Niacin is a simple derivative of
pyridine.
Active Form

Active forms of niacin are:

 Nicotinamide adenine dinucleotide (NAD+)

 Nicotinamide adenine dinucleotide phosphate (NADP+)

Sources

 Yeast, liver, legumes and meats are major sources of niacin.

 Limited quantities of niacin can also be obtained from the

metabolism of tryptophan. For every 60 mg of tryptophan, 1

mg equivalent of niacin can be generated.

Nutritional Requirement

 The RDA for niacin is 15 to 20 mg.

 Tryptophan can only provide 10% of the total niacin

requirement.
Functions

 Niacin is a precursor of coenzymes, nicotinamide adenine

dinucleotide (NAD+) and nicotinamide adenine

dinucleotide phosphate (NADP+).

 NAD+ and NADP+ are involved in various oxidation and

reduction reactions.

 They are, therefore involved in many metabolic pathways

of carbohydrate, lipid and protein.

 Generally, NAD+ catalyze oxidation-reduction reactions
in oxidative path- ways, e.g. citric acid cycle and
glycolysis.

 Whereas NADP+ are often found in pathways concerned

with reductive synthesis, e.g. synthesis of cholesterol,
fatty acid and pentose phosphate pathways.
 Deficiency Manifestation
Pellagra

 Deficiency of niacin in human causes pellagra, a

disease involving :

 Skin

 Gastrointestinal tract

 Central nervous system.

 The symptoms of pellagra are characterized by three ‘Ds’:

1. Photosensitive Dermatitis

2. Diarrhea

3. Depressive psychosis (dementia) and if not treated death.

 Untreated pellagra is fatal.

Niacin deficiency occurs in:

 Population dependent on maize (corn) or sorghum

(jowar) as the staple food.

 In maize, niacin is present in bound form niacytin.

 Sorghum content high amount of leucine. Excess of

leucine inhibit conversion of tryptophan to niacin
 Deficiency of vitamin B6 (pyridoxal phosphate) leads to
niacin deficiency as it is involved as a coenzyme in the
pathway of synthesis of niacin from tryptophan.

 Malignant carcinoid syndrome in which tryptophan is

diverted to formation of serotonin.

 In Hartnup disease, a genetic disorder in which tryptophan

absorption and trans- portation is impaired.
The conversion of tryptophan into nicotinic acid.
 Pantothenic Acid (Vitamin B5)
The name pantothenic acid is derived from the Greek word
‘pantothene,’ meaning from “everywhere” and gives an
indication of the wide distribution of the vitamin in foods.
Structure

Pantothenic acid is formed by combination of

pantoic acid and β-alanine

Structure of pantothenic acid.

Active form

1. Coenzyme-A (CoA-SH)

2. Acyl carrier protein (ACP).

Source

Eggs, liver, yeast, wheat germs, cereals, etc. are impor- tant
sources of pantothenic acid, although the vitamin is widely
distributed.
Nutritional Requirement

The RDA of pantothenic acid is not well established. A

daily intake of about 5–10 mg is advised for adults
Functions
 Pantothenic acid is a component of coenzyme-A (CoA-
SH) and acyl carrier protein (ACP).
 The thiol (-SH) group of CoA-SH and ACP acts as a
carrier of acyl groups.
 Coenzyme-A participates in reactions concerned with:
– Reactions of citric acid cycle
– Fatty acid synthesis and oxidation
– Synthesis of cholesterol
– Utilization of ketone bodies.
 ACP participate in reactions concerned with fatty acid
synthesis.
Deficiency Manifestations

 No clear-cut case of pantothenic acid deficiency has been

reported.
 Clinical signs observed in experimentally induced
deficiencies are:
Paraesthesia (abnormal tingling sensation)
Headache
Dizziness
Gastrointestinal malfunction.
 Pyridoxine (Vitamin B6)
Structure

 Vitamin B6 consists of a mixture of three different closely

related pyridine derivatives namely:

1. Pyridoxine

2. Pyridoxal

3. Pyridoxamine.

 All the three have equal vitamin activity, as they can be

interconverted in the body.

Structure of three different forms of vitamin B
Active Form of Vitamin B6

Pyridoxal phosphate (PLP) is the active form of vitamin

B6.
Sources

 Pyridoxine occurs mainly in plants, whereas pyridoxal

and pyridoxamine are present mainly in animal
products.

 Major dietary sources of vitamin B6 are yeast,

unrefined cereals, pulses, meat, poultry fish, potatoes
and vegetables.

 Dairy products and grains contribute lesser amounts.

Nutritional Requirement

 The RDA for vitamin B6 is 1.6 to 2.0 mg.

 Requirements increase during pregnancy and lactation

Functions
Active form of vitamin B6, pyridoxal phosphate (PLP)
acts as coenzyme in amino acid metabolism. For
example:
– Transamination
– Decarboxylation
– Nonoxidative deamination
– Trans-sulfuration
– Condensation reactions of amino acids.
 Transamination reactions

Transamination reactions are catalyzed by transaminases

and PLP acts as coenzyme converting amino acid to keto
acid, e.g. aspartate transaminase (AST) and alanine
transaminase (ALT)

 Non-oxidative deamination

Hydroxyl group contain- ing amino acids (serine,

threonine) are non-oxidatively deaminated to α-keto acids
and ammonia, which requires PLP.
 Decarboxylation reaction
PLP acts as coenzyme in decarboxylation of some amino
acids. The amino acids are decarboxylated to corresponding
amines.
– γ-Amino butyric acid (GABA)
– Serotonin and melatonin
– Histamine
– Catecholamines (dopamine, norepinephrine and
epinephrine)
 Trans- sulfuration reaction:

PLP is a coenzyme for cystathionine synthase involved in

synthesis of cysteine from methionine In these reactions
transfer of sulfur from methionine to serine occurs to
produce cysteine.

 Condensation reactions

Pyridoxal phosphate is required for the condensation

reaction of L-glycine and succinyl CoA in the synthesis of
heme.
 Other reactions requiring PLP are:

– For niacin coenzyme (NAD+/NADP+) synthesis

from tryptophan

– For synthesis of serine from glycine

– FOR the synthesis of sphingomyelin.

Deficiency Manifestations

 Vitamin B6 deficiency causes neurological disorders such

as depression, nervousness and irritability.

 Severe deficiency of pyridoxine causes epileptic seizures

(convulsions) in infants.

 Demyelination of nerves causes peripheral neuro- pathy.

 Vitamin B6 deficiency causes hypochromic micro- cytic

anemia due to decreased heme synthesis.
The commonest cause of pyridoxine deficiency is:

 Drug antagonism, e.g. isoniazide (INH), used in the

treatment of tuberculosis and penicillamide used in the
treatment of Wilson’s disease and rheumatoid arthritis can
combine with pyridoxal phosphate forming an inactive
derivative with pyridoxal phosphate.

 Alcoholism: Alcoholics may be deficient owing to

metabolism of ethanol to acetaldehyde, which stimulates
hydrolysis of the phosphate of the pyridoxal phosphate
 Biotin

Biotin was known formerly as vitamin H.

Structure
It consists of a tetrahydro-thiophene ring bound to an
imidazole ring and a valeric acid side chain.
Structure of biotin.
Sources

 It is widely distributed in foods.

 Liver, kidneys, vegetables and egg yolk are the

important sources of biotin.

 Biotin is also synthesized by intestinal bacteria.

Active Form of Biotin

Enzyme-bound biotin, biocytin is an active form of biotin.

Biotin is covalently bound to ε- amino group of lysine of an
enzyme to form biocytin.

Nutritional Requirements

A daily intake of about 150–300 mg is recommended for

adults. Biotin is synthesized by intestinal micro- organisms in
such a large quantities that a dietary source is probably not
necessary.
Functions

Biotin is a coenzyme of carboxylase reactions, where it is a

carrier of CO2.

 Conversion of acetyl-CoA into malonyl-CoA catalyzed

by acetyl-CoA carboxylase in fatty acid synthesis.

 Conversion of pyruvate into oxaloacetate, catalyzed by

pyruvate carboxylase in gluconeogenesis .
 Conversion of propionyl-CoA to D-methyl malonyl-CoA
catalyzed by propionyl-CoA carboxylase in the pathway
of conversion of propionate to succinate.

 Catabolism of branched chain amino acid catalyzed by β-

methylcrotonyl-CoA carboxylase
Biotin Independent Carboxylation Reaction

 Formation of carbamoyl phosphate by carbamoyl

phosphate synthetase in urea cycle.

 Addition of CO2 to form C6 in purine ring.

 Conversion of pyruvate to malate by malic enzyme.

Deficiency Manifestation

 Since biotin is widely distributed in plant and animal

foods and intestinal bacterial flora supply adequate
amounts of biotin, the natural deficiency of biotin is not
well characterized in humans.

 The experimentally induced symptoms of biotin

deficiency are nausea, anorexia, glossitis, dermatitis,
alopecia (loss of hair), depression and muscular pain.
Deficiency of biotin occurs in:

 The people with the unusual dietary habit of consuming

large amounts of uncooked eggs. Egg white contains the
glycoprotein avidin, which binds the imidazole group of
biotin and prevents biotin absorption.

 Use of antibiotics, that inhibit the growth of intestinal

bacteria, eliminates this source of biotin and leads to
deficiency of biotin.
 Folic Acid
Structure
 Folic acid consists of three components:
1. Pteridine ring,
2. P-amino benzoic acid (PABA) and
3. L-glutamic acid
 In a folic acid molecule, the number of glutamic acid
residues varies from one to seven. Folic acid usually
has one glutamic acid residue.
The structure and numbering of atoms of folic acid.
Active Form of Folic Acid

Tetrahydrofolate (THF) is the active form of folic acid.

Source

 Folic acid is found in green leafy vegetables, liver, yeast.

 The word folate is related to folium which means leaf in

Latin.
Nutritional Requirements

 The RDA of folate is 200 mg.

 Requirements increase during pregnancy and

lactation.
Formation of tetrahydrofolate from folic acid.
Functions

 Tetrahydrofolate (THF) acts as a carrier of one-

carbon units. The one carbon units are:

Methyl CH3

Methylene CH2

Methenyl CH

Formyl CHO

Formimino CH = NH
 One carbon unit binds to THF through N5 or N10 or both
N5, N10 position.

 The THF coenzymes serve as acceptors or donors of one

carbon units in a variety of reactions involved in amino
acid and nucleic acid metabolism.
Five major reactions in which THF is involved are:

1. Conversion of serine to glycine:

The conversion of serine to glycine is accompanied

by the formation of N5,N10- methylene THF.

2. Synthesis of thymidylate (pyrimidine nucleo- tide):

The enzyme thymidylate synthase that converts

deoxyuridylate (dUMP) into thymidy- late (TMP)
uses N5, N10- methylene THF as the methyl donor
for this reaction.
3. Catabolism of histidine :
Histidine in the course of its catabolism is converted into
formimino- glutamate(FIGLU). This molecule donate the
formimino group to THF to produce N 5 formimino THF.
4. Synthesis of purine:
N5-Formyl THF inter- mediate formedin histidine
catabolism is used in the biosyn- thesis of purineand
therefore in the formation of both DNA and RNA.
5. Synthesis of methionine from homocysteine:
Homocysteine is converted to methionine in presence of
N5-methyl THF, and vitamin B12.
– In this reaction the methyl group bound to cobalamin
(Vitamin B12) is transferred to homocysteine to form
methionine and the cobalamin then removes the methyl
group from N5-methyl THF to form THF.

– This step is essential for the liberation of free THF and

for its repeated use in one carbon metabolism. In B12
deficiency, conversion of N5-methyl THF to free THF is
blocked.
The combined role of vitamin B12 and folate and folate
trap.
Deficiency Manifestations
 Megaloblastic or macrocytic anemia

 Accumulation and excretion of FIGLU in the urine

 Hyperhomocysteinemia

 Neural tube defect in foetus

Excretion of FIGLU in folic acid deficiency.
 Cobalamin (Vitamin B12)
Structure

 Vitamin B12 bears a complex corrin ring (containing

pyrrols similar to porphyrin), linked to a cobalt atom
held in the center of the corrin ring, by four coordination
bonds with the nitrogen of the pyrrole groups.
 The remaining coordination bonds of the cobalt are
linked with the nitrogen of dimethylbenzimidazole
nucleotide and sixth bond is linked to either methyl or
5'-deoxy- adenosylor hydroxy group to form
methyl- cobalamin, adenosylcobalamin or
hydroxycobalamin respectively
Structure of Vit B12.
(R: either
methyl
or
deoxyadenosyl
or
hydroxy group)
Active form of Vitamin B12

 Methylcobalamin

 Deoxyadenosylcobalamin.

Sources

 Dietary sources of vitamin B12 are of animal origin ;

meat, eggs, milk, dairy products, fish, poultry, etc.

 Vitamin B12 is absent in plant foods.

 Humans obtain small amounts of B12 from intestinal

flora.
Nutritional Requirements (RDA )

3 μg with higher allowances for pregnancy and

lactating women.
Absorption, Transport and Storage
• The intestinal absorption of vitamin B12 requires an
intrinsic factor (IF), a glycoprotein secreted by parietal
cells of the stomach.
• In stomach IF binds the dietary vitamin B12 to form
vitamin B12-IF complex.
• This complex binds to specific receptors on the surface of
the mucosal cells of the ileum.
• After binding to the receptor, the bound vitamin B12 is
released from the complex and enters the illeal mucosal
cells through a Ca2+ dependent process.
Functions

There are only two human enzyme systems that are

known to require vitamin B12 coenzyme.

1. Isomerization of methylmalonyl-CoA to succinyl-CoA

2. Conversion of homocysteine to methionine

Role of vit B12 in
isomerization of
methylmalonyl-CoA to
succinyl-CoA
Role of vit B12 conversion of homocysteine to methionine

This is the only mammalian reaction require both vitamins

Deficiency Manifestations

 Pernicious anemia

 Megaloblastic anemia

 Methylmalonic aciduria

 Neuropathy (sub acute combined degeneration,

SCD)

 Folate trap
 Vitamin B12 Deficiency Causes
Functional Folate Deficiency: The Folate Trap

 S-adenosyl methionine forms homocysteine, which may

be remethylated by methyltetrahydrofolate catalysed by
methionine synthase, a vitamin B12 dependent enzyme.

 Impairment of methionine synthase in vitamin B12

deficiency results in the accumulation of
methyltetrahydrofolate that cannot be used and cannot be
converted to free THF.
 Thus, most of THF is irreversibly “trapped” as methyl
THF.

 There is therefore functional deficiency of folate,

secondary to the deficiency of vitamin B12.

 Folate trap creates folate deficiency and an adequate

supply of free THF is not available for the synthesis of
purine and pyrimidine bases.
 Vitamin C (Ascorbic Acid)
Structure

 It is a six-carbon sugar derivative .

 Humans cannot synthesize ascorbic acid, due to lack of

the enzyme gluconolactone oxidase.
Structure of ascorbic acid.
Active Form of Ascorbic Acid

Ascorbic acid itself is an active form.

Sources

 The main dietary sources of vitamin C are leafy

vegetables and fruits, especially citrus fruits, strawberries,
tomatoes, spinach and potatoes.

 Cereals contain no vitamin C.

 Animal tissues and dairy products are very poor sources.

Nutritional Requirements

The recommended daily allowance is about 60–70 mg.

Additional intakes are recommended for women during
pregnancy and lactation.
Functions
 Vitamin C is the coenzyme for two groups of
hydroxylases.

–Copper containing hydroxylases

–α-ketoglutarate linked iron containing

hydroxylases

 Ascorbic acid has specific roles in the number of non-

enzymatic effects as result of its action as a reducing
agent and oxygen radical quencher.
Role of Ascorbic acid in the copper containing hydroxylases

 Dopamine β-hydroxylase is a copper containing enzyme

involved in the synthesis of the catecholamines
(norepinephrine and epinephrine), from tyrosine in the
adrenal medulla and central nervous system.

 A number of peptide hormones have a carboxy terminal

amide that is derived from a terminal glycine residue. This
glycine is hydroxylated on the α-carbon by a copper
containing enzyme, peptidylglycine hydroxylase, which
again, requires ascorbate for reduction of Cu2+.
Role of Ascorbic acid in the iron containing hydroxylases

 Proline hydroxylases and lysine hydroxylases are required for the

postsynthetic modification of procollagen to collagen.

 Aspartate β-hydroxylase is required for the postsynthetic

modification of the precursor of protein C.

 Vitamin K-dependent protease that hydrolyses activated factor V

in the blood clotting cascade.

 Trimethyllysine and γ-butyrobetain hydroxylases are required for

the synthesis of carnitine.
Non-enzymatic effects as result of its action as a reducing

agent and oxygen radical quencher

 Ascorbic acid is a water soluble antioxidant:

– It reduces oxidized vitamin E (tocopherol) to

regenerate functional vitamin E.

– Vitamin C thought to be involved in the prevention of

atherosclerosis and coronary heart disease by

preventing oxidation of LDL.

 – Antioxidant property of vitamin C is also associated

with prevention of cancer by inhibiting nitrosamine

formation from naturally occurring nitrates during

digestion.

• In addition to other roles of vitamin C, it enhances the

absorption of inorganic iron. Ascorbic acid facilitates the
absorption of iron from intestine by reducing it to the
Fe++ (ferrous) state.
Deficiency Manifestation

 Deficiency has been observed in infants receiving un-

supplemented cow’s milk and in infants receiving breast
milk from deficient mother.

 Deficiency occurs most commonly in the elderly,

especially those who do not eat fresh fruits and vegetables
and who tend to cook in frying pans, the combination of
heat and large area of food in contact with air irreversibly
oxidizes the vitamin and loses its biological activity.

 Deficiency also can occur in iron overload.

 Scurvy

 Deficiency of ascorbic acid causes scurvy.

 Vitamin C is required for formation of collagen, where it is

needed for the hydroxylation of proline and lysine residues, of
protocollagen.

 Hydroxyproline and hydroxylysine are essential for the

collagen cross-linking and collagen strength and stability.

 Since vitamin C is required for normal collagen formation,

vitamin C is also involved in bone and dentin formation as well
as wound healing process.
Symptoms of scurvy

 Symptoms of scurvy are related to deficient collagen

formation. These include:

– Fragility of vascular walls causing bleeding tendency,

muscle weakness, soft spongy, swollen bleeding

gums, loosening of teeth.

– Abnormal bone development and osteoporosis. In

children bone formation is impaired.

– Poor wound healing.

– Anemia due to impaired erythropoiesis.

– Milder forms of vitamin C deficiency are more

common and manifestation of such include easy

bruising (contusion) and formation of petechiae both

due to increased capillary fragility.

 Vitamin A
Structure

 Vitamin A contains a single 6-membered ring to which is

attached an 11-carbon side chain.

 Vitamin A is an alcohol (retinol), but can be converted

into an aldehyde (retinal), or acid (retinoic acid).
Structure of vitamin A, retinol.
Active Form

Vitamin A consists of three biologically active molecules

which are collectively known as retinoids.

1. Retinol: Primary alcohol (CH2OH) containing form

2. Retinal: Aldehyde (CHO) containing form

3. Retinoic acid: Carboxyl (COOH) containing form

 Each of these compounds are derived from the plant precursor
molecule, β-carotene.

 β-carotene which consists of two molecules of retinal linked

at their aldehyde ends is also referred to as the provitamin
form of vitamin A.

 The retinol and retinal are interconverted by enzyme retinal

aldehyde reductase.

 The retinoic acid is formed by oxidation of retinal. The

retinoic acid can not be reduced to either retinol or retinal
Conversion of β-carotene (provitamin) to biologically active forms of
vitamin A.
Sources

 The richest dietary sources are fish liver oils (cod liver
oil). Meat is rather low in vitamin A.

 Other good sources are milk and dairy products, dark-

green leaves, such as spinach and yellow and red fruits
and vegetables, such as carrots, tomatoes, and peaches
etc.
Nutritional Requirements

The RDA of vitamin A for adults is 800–1000 retinol

equivalents. (1 retinol equivalent = 1 mg retinol = 6 mg β-
carotene).
 Functions of Vitamin A

 Vitamin A is required for a variety of functions such as

– Vision

– Cell differentiation and growth

– Mucus secretion

– Maintenance of epithelial cells

 Different forms of the vitamin have different functions.

– Retinal and retinol are involved in vision.

– Retinoic acid is involved in cellular differentiation

and metabolic processes.

– β-carotene is involved in antioxidant function.

Role of Vitamin A in Vision

 The role of vitamin A in vision has been known through

the studies of G Wald, who received the Nobel Prize in
1943

 The cyclic events occur in the process of vision, known

as rhodopsin cycle or Wald’s visual cycle
 Both rod and cone cells of retina contain a photoreceptor

pigment in their membrane and vitamin A is a component

of these pigments.

 Rhodopsin or visual purple, the visual pigment of rod

cells in the retina consists of 11-cis-retinal bound to
protein opsin.
Wald’s visual cycle
 When rhodopsin absorbs light, the 11-cis-retinal is
converted to all-trans retinal.

 The isomerization is associated with a conforma- tional

change in the protein opsin.

 Conformational changes in opsin generates a nerve

impulse that is trans- mitted by the optic nerve to the brain.

 This is followed by dissociation of the all-trans retinal

from opsin
 The all-trans retinal is immediately isomerized by retinal
isomerase to 11-cis-retinal.

 This combines with opsin to regenerate rhodopsin and

complete the visual cycle.

 The conversion of all-trans retinal to 11-cis-retinal is

incomplete and therefore remaining all-trans retinal
which is not converted to 11-cis-retinal is converted to all-
trans retinol by alcohol dehydrogenase and is stored in the
liver.
 When needed, retinol re-enters the circulation and is taken
up by the retina, where it is converted back to 11-cis-
retinal which combines with opsin again to form
rhodopsin
Dark adaptation time

The time taken for regeneration of rhodopsin is known as

dark adaptation time. Dark adaptation time is increased in
vitamin A deficient individuals
Role of Vitamin A in Color Vision
 Color vision is mediated by three pigments called
porphyropsin, iodopsin and cyanopsin and are sensitive to
the three essential colours: red, green and blue
respectively.
 All these pigments consist of 11-cis-retinal bound to
protein opsin .
 When light strikes retina, it bleaches one or more of these
pigments, depending on the color quality of the light.

 The pigments are converted to all-trans retinal, and the

protein moiety opsin is released as in the case of
rhodopsin.
 This reaction gives rise to the nerve impulse that is read
out in the brain as color:

– Red if porphyropsin is split

– Green if iodopsin is split

– Blue if cyanopsin is split.

 If mixtures of the three are converted, the color read out

in the brain depends on the proportions of the three split.
Cellular Differentiation and Metabolic Effect

 Retinoic acid is an important regulator of gene

expression especially during growth and development.

 Retinoic acid is essential for normal gene expression

during embryonic development such as cell
differentiation in spermatogenesis and in the
differentiation of epithelial cells.
 Retinoic acids exert a number of metabolic effects on tissues.

These include:

– Control of biosynthesis of membrane glycoproteins

and glycosaminoglycans (mucopolysaccharide)

necessary for mucus secretion. The normal mucus

secretion maintains the epithelial surface moist and

prevents keratinization of epithelial cell.

– Control of biosynthesis of cholesterol.

Antioxidant Function

 β-carotene is an antioxidant and may play a role in

trapping free radicals in tissues.

 The antioxidant property of lipid soluble vitamin A may

account for its possible anticancer activity.

 High levels of dietary carotenoids have been associated

with a decreased risk of cardiovascular disease
 Deficiency Manifestation

 Clinically, degenerative changes in eyes and skin are

observed commonly in individuals with vitamin A
deficiency.

 Vitamin deficiency may be primary (dietary

insufficiency) or secondary.
The causes of secondary deficiency may include:

– Impaired absorption of lipids

– Failure to synthesize apo B-48 and therefore inability

to form chylomicrons into which vitamin A is
normally incorporated after absorption.

– Lack of lipase, as in pancreatitis.

– Failure in converting β - carotene to retinol; because

of an enzyme defect.
– Impaired storage in hepatic cell in liver disease.

– Failure to synthesize retinol binding proteins, thus

affecting transport to target tissues.
Effect on Vision

The earliest symptoms of vitamin A deficiency is:

– Impaired dark adaptation or night blindness

(nyctalopia)

– Poor vision in dim light

– Xerophthalmia.
Night blindness (nyctalopia)

 This is characterized by loss of vision in night (in dim or

poor light) since dark adaptation time is increased.

 Prolonged deficiency of vitamin A leads to an irreversible

loss of visual cells.

 Severe vitamin A deficiency causes dryness of cornea and

conjunctiva, a clinical condition termed as xerophthalmia
(dry eyes).
 If this situation prolongs, keratinization and ulceration of
cornea takes place

 This results in destruction of cornea. The cornea becomes

totally opaque resulting in permanent loss of vision
(blindness), a clinical condition termed as keratomalacia.

 White opaque spots develop on either side of cornea in

vitamin A deficiency are known as Bitot’s spot.
Effect on Skin and Epithelial Cells

 Vitamin A deficiency causes keratinization of epithelial

cells of skin which leads to keratosis of hair follicles,
and dry, rough and scaly skin.

 Keratinization of epithelial cells of respiratory, urinary

tract makes them susceptible to infections.
Other Symptoms of Vitamin A Deficiency

 Failure of growth in children.

 Faulty bone modelling producing thick cancellous

(spongy) bones instead of thinner and more compact ones.

 Abnormalities of reproduction, including degeneration of

the testes, abortion or the production of malformed
offspring.
Hypervitaminosis A

Excessive intakes of vitamin A lead to accumulation beyond the

capacity of intracellular binding proteins. Unbound vitamin A
causes membrane lysis and tissue damage. Symptoms of toxicity
affect:

 The central nervous system and leads to headache, nausea,

ataxia, and anorexia. These all associated with increased
cerebrospinal fluid pressure.

 The liver: hepatomegaly with histological changes and

hyperlipidemia
 Calcium homeostasis: thickening of the long bones,

hypercalcemia, and calcification of soft tissues, bone and

joint pain,

 The skin: loss of hair (alopecia), scaly and rough skin.

 In pregnant women, the hypervitaminosis A may cause

congenital malformation in growing fetus (teratogenic

effect).
Why Vitamin A is Considered as a Hormone?

 Within cells both retinol and retinoic acid function by binding

to specific receptor proteins present in the nucleus of target
tissues.

 Following binding, the receptor-vitamin complex interacts

with several genes involved in growth and differentiation and
affects expression of these genes.
 Vitamin D (Cholecalciferol)

Vitamin D is also known as calciferol because of its role

in calcium metabolism and antirachitic factor because it

prevents rickets.
 Vitamin D could be thought of as a hormone
rather than a vitamin

 As it can be synthesized in the body

 It is released in the circulation

 Has distinct target organs

 Action of vitamin D is similar to steroid hormones. It

binds to a receptor in the cytosol. Following binding, the
receptor vitamin complex interacts with DNA to
stimulate the synthesis of calcium binding protein.
 Structure

Vitamin D is a steroid compound. The naturally produced

vitamin D3 or cholecalciferol is obtained from animal
sources in the diet, or made in the skin by the action of
ultraviolet light from sunlight on
Structure of 1,25-dihydroxycholecalciferol an active
form of vitamin D3.
The formation of vitamin D3 in the body and
vitamin D2 commercially.
Active Form of Vitamin

 Cholecalciferol is an inactive form of vitamin D.

 It needs further metabolism to produce the active form of

the vitamin. 1, 25 dihydroxycholecalciferol also known
as calcitriol is the active form of vitamin D.
Activation of vitamin D.
Sources

 Best sources are cod liver oil and often fish oils and
sunlight induced synthesis of vitamin D3 in skin.

 Egg yolk and liver are good sources.

Nutritional Requirement

The daily requirements of vitamin D is 200–400 IU.

Functions

 Vitamin D (Calcitriol) plays an essential role as a

hormone in the regulation of calcium and phosphorus
metabolism.

 It maintains the normal plasma level of calcium and

phosphorus by acting on intestine, kidneys and bones.
 Action of calcitriol on intestine

It increases the plasma calcium and phosphorus

concentration by stimulating the absorption of
calcium and phosphorus from the intestine.

 Action of calcitriol on kidney

It stimulates the reabsorption of calcium and

phosphorus from the kidney and decreases their
excretion.
 Action of calcitriol on bone

– Calcitriol promotes the mineralization of bones by

deposition of calcium and phosphorus.

– Calcitriol along with PTH stimulates the mobilization

of calcium and phosphorus from bone.
Sites of formation of vitamin D3 to its metabolically
active form 1,25-dihydroxychole- calciferol and its
function.

1,25-DHCC: 1,25-dihydroxycholecalciferol;

PTH: parathyroid hormone

Deficiency Manifestation

Deficiency of vitamin D causes:

– Rickets (rachitis) in growing children and

– Osteomalacia in adults.
Rickets

 Rickets is characterized by formation of soft and pliable

bones due to poor mineralization and calcium deficiency.

 Due to softness, the weight bearing bones are bent and

deformed.

 The main features of the rickets are, a large head with

protruding forehead, pigeon chest, bow legs, (curved
legs), knock knees and abnormal curvature of the spine
(kyphosis).
Bowing of legs in rickets.
 Rachitic children are usually anemic or prone to
infections. Rickets can be fatal when severe.

 Rickets is characterized by low plasma levels of calcium

and phosphorus and high alkaline phosphatase activity.
Osteomalacia (Adult Rickets)

 Deficiency of vitamin D in adults causes osteomalacia.

This is a condition similar to that of rickets.

 Osteomalacia characterized by demineralization of

previously formed bones, Demineralization of bones
makes them soft and susceptible to fractures.

 Osteomalacia especially occurs in women who have little

exposure to sunlight, and especially after several
pregnancies
Renal Rickets (Renal Osteodystrophy)

 In chronic renal failure synthesis of calcitriol in kidney is

impaired. As a result, the deficiency of calcitriol occurs
which leads to hypocalcemia and hyperphosphatemia.

 It can be treated by oral or intravenous administration of

calcitriol (active form of vitamin D).
Vitamin D Resistant Rickets

 As the name implies, this is a disease which does not

respond to treatment with vitamin D.

 There are various possible causes of this condition and

all involve a defect in the metabolism or mechanism of
action of 1,25 dihydroxycholecalciferol.
– Due to defective vitamin D receptor

– Due to a defective 1, α-hydroxylase activity in kidney

– Due to liver disease and kidney failure as the

production of 25-hydroxycholecalciferol and 1,25
dihydroxycholecalciferol respectively will be
inefficient in the damaged tissue
Hypervitaminosis D

 High doses of vitamin D over a long period are toxic.

 The early symptoms of hypervitaminosis D include nausea,

vomiting, anorexia, increased thirst, loss of weight, etc.

 Hypercalcemia is seen due to increased bone resorption and

intestinal absorption of calcium.

 The prolonged hypercalcemia causes calcification of soft

tissues and organs such as kidney and may lead to formation

of stones in the kidneys.

 Vitamin E (Tocopherol)

Structure

Vitamin E consists of eight naturally occurring tocopherols,

of which α-tocopherol is the most active form
Sources

The major dietary sources of vitamin E are fats and oils.

The richest sources are germ oil, corn oil, fish oil, eggs,
lettuce and alfalfa.

Nutritional Requirements

A daily consumption of about:

10 mg (15 IU) of α-tocopherol for a man

8 mg (12 IU) for α- woman is recommended.

One mg of α-tocopherol is equal to 1.5 IU.

Functions

 Vitamin E acts as a natural antioxidant by scavenging

free radicals and molecular oxygen.

 Vitamin E is important for preventing peroxidation of

polyunsaturated fatty acids in cell membranes.

 Protection of erythrocyte membrane from oxidant is the

major role of vitamin E in humans. It protects the RBCs
from hemolysis.
 Vitamin E also helps to prevent oxidation of LDL.
Oxidized LDL may be more atherogenic than native LDL
and thus vitamin E may protect against athreo- matous
coronary heart disease.

 Whether vitamin E affects human fertility is unknown.

 In animals, vitamin E is required for normal reproduction

and prevents sterility.
Deficiency Manifestation

 The major symptom of vitamin E deficiency in human is

hemolytic anemia due to an increased red blood cell fragility.

 Another symptom of vitamin E deficiency is retrolental

fibroplasia (RLF) observed in some premature infants of low
birth weight. Children with this defect show neuropathy.

Hypervitaminosis E

 Unlike other fat soluble vitamins such as A and D, vitamin E

does not seem to have toxic effects.
 Vitamin K

 This vitamin is called an anti-hemorrhagic factor as its

deficiency produced uncontrolled hemorrhages due to
defect in blood coagulation.

 In 1929, H Dam gave the name koagulation vitamin from

the Danish word koagulation. It is now called vitamin K.
Structure

 Vitamin K1 or phylloquinone derived from plant.

 Vitamin K2 or menaquinones, produced by

microorganisms.

 Vitamin K3 or menadione is a synthetic product

Structure of vitamin K.
Sources

 Excellent sources are cabbage, cauliflower, spinach and

other green vegetables.

 Good sources include tomatoes, cheese, dairy products,

meat, egg yolk, etc.

 The vitamin is also synthesized by microorganisms in the

intestinal tract.

Nutritional Requirements

The suggested intake for adults is 70–140 mg/day.

Functions of Vitamin K
 Vitamin K plays an important role in blood coagulation.
 Vitamin K is required for the activation of blood clotting
factors, prothrombin (II), factor VII, IX and X.
 These blood clotting proteins are synthesized in liver in
inactive form, and are converted to active form by
vitamin K dependent carboxylation reaction.
 In this, vitamin K dependent carboxylase enzyme adds
the extra carboxyl group at  -carbon of glutamic acid
residues of inactive blood clotting factors.
Role of vitamin K in the gamma-carboxylation of glutamyl residues of inactive
proteins of blood-clotting factors.
 Vitamin K is also required for the carboxylation of
glutamic acid residues of osteocalcin, a Ca2+ binding
protein present in bone.

 Anticoagulants, Dicumarol and warfarin are structurally

similar to vitamin K and inhibit the action of vitamin K.
Deficiency Manifestation

Vitamin K is widely distributed in nature and its production

by the intestinal micro flora ensures that dietary deficiency
does not occur.

 Vitamin K deficiency is associated with hemorrhagic

disease.

 In vitamin K deficiency, clotting time of blood is

increased. Uncontrolled hemorrhages occur on minor
injuries as a result of reduction in prothrombin and other
clotting factors.
Vitamin K deficiency, however, is found in:

 Patients with liver disease and biliary obstruction. Biliary

obstruction inhibits the entry of bile salts to the intestine.

 In new-born infants, because the placenta does not pass

the vitamin to the fetus efficiently, and the gut is sterile
immediately after birth.

 Following antibiotic therapy that sterilizes the gut.

 In fat malabsorption, that impairs absorption of vitamin

K.
Hypervitaminosis K

Excessive doses of vitamin K produce a hemolytic anemia

(due to increased breakdown of RBCs) and jaundice (in
infants).
Thank you