Biochemistry and Clinical Pathology Vitamins and Coenzymes

VITAMINS
Vitamins: Vitamins are naturally occurring organic micronutrients required for normal growth and
development of living organisms. They are accessory, indispensable food factors and their
deficiency leads to disorders.
Some of the vitamins are lipophilic in nature and are usually present in the lipids of natural
foods. They are called fat soluble vitamins and include vitamins A, D, E and K. Hydrophilic
vitamins, called water soluble vitamins include vitamins of B complex group and (vitamin C).
Classification: Vitamins are classified into two groups based on their solubility.
A. Fat soluble vitamins: These are the lipophilic vitamins usually found in the lipids of natural
foods. It includes;
1. Vitamin A – Retinol and dehydroretinol
2. Vitamin D – Calciferol, Ergocalciferol and Cholecalciferol
3. Vitamin E – Tocopherols
4. Vitamin K – Phylloquinone, Menaquinone etc.
B. Water soluble vitamins: These are the hydrophilic vitamins and include vitamins of B
complex group and vitamin C (Ascorbic acid). B complex group includes;
1. Thiamine (Vitamin B1)
2. Riboflavin (Vitamin B2)
3. Niacin (Vitamin B3)
4. Pyridoxin (Vitamin B6)
5. Pantothenic acid (Vitamin B5)
6. Cyanocobalamine (Vitamin B12)
7. Lipoic acid
8. Biotin
9. Folic acid
10. Inositol
11. Para amino benzoic acid
12. Choline
Vitamin A:
Synonyms: Antixerophthalmic factor
Dietary sources: Fish liver oils, liver, milk, egg and cheese contain preformed vitamin A. The plant
sources of vitamin A contain precursors of vitamin A called carotenes. β carotene is a dimer
of vitamin A and gives two molecules of vitamin A on cleavage. Fruits like carrot, sweet
potato, apricot, yellow peaches and green leafy vegetables are rich in carotenes.
Chemistry: Vitamin A is a complex primary alcohol. It is a polyisoprenoid compound with a β inone
(cyclohexenyl) ring. It occurs in two forms ie. Retinol called vitamin A1 and dehydroretinol
called vitamin A2.
H3C CH3 CH3 CH3 H3C CH3 CH3 CH3
CH 2OH CH 2OH

CH3 Retinol (Vitamin A 1) CH3 Dehydroretinol (Vitamin A 2)

Dehydroretinol contains an additional double bond in the β inone ring. The aldehyde form
of retinol is called retinal while its acid form is called retinoic acid.

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

Biological role:
1. Vitamin A is involved in formation of certain pigments required for dim light vision.
2. It plays important role in biosynthesis of certain glycoproteins and muco-polysaccharides.
3. It is also involved in regulation of growth and development of cells.
4. It is also involved in mobilization of iron from liver to form hemoglobin.
5. It protects cells from infections and cancer.
6. It plays important role in normal development of epithelial tissue of salivary gland, tongue,
respiratory tract, genitourinary tract, eyes etc.
Deficiency disorder: Depending on age, the daily dietary requirement of vitamin A varies between
1500 to 5000 IU (1 IU of vitamin A is equivalent to 0.3 μg of retinol). Inadequate availability
of vitamin A in diet leads to following deficiency states.
1. Deficiency of vitamin A leads to Nyctalopia (Night blindness), Xerophthalmia and
Keratomalacia.
2. It causes follicular hyperkeratosis of skin and mucous membrane (follicular conjunctivitis).
3. Prolonged deficiency of vitamin A leads to keratinizing metaplasia of epithelium of nose,
respiratory mucosa, esophagus and genitourinary tract.
4. It also leads to formation of urinary calculi (Urolithiasis)
Xerophthalmia: Xeropthalmia is a disorder of deficiency of vitamin A. It is characterized by
thickening of bulbar conjunctiva and loss of its transparency with yellowish pigmentation.
The keratinisation of ocular tissue ultimately leads to blindness.
Keratomalacia: Keratomalacia is a disorder of deficiency of vitamin A. It is characterized by
softening of the cornea with ulceration and necrosis. Due to keratinisation of the epithelium
of cornea, the vision becomes defective.
Nyctalopia (Night blindness): Nyctalopia is a disorder of deficiency of vitamin A. It is one of the
earliest signals of deficiency of vitamin A. It is characterized by inability to see in dim light.
Continued supply of retinol is essential for formation of rhodopsin which is involved in dim
light vision. The deficiency of vitamin A impairs biosynthesis of rhodopsin and thus results in
night blindness.
Vision cycle and role of vitamin A: Retina of eye contains two types of cells ie. Cone cells which are
responsible for bright light vision and rod cells which are responsible for dim light vision. The
rod cells contain a pigment – Rhodopsin which contains 11- cis retinal (retinene) coupled with
a protein opsin. This pigment is essential for dim light vision.
When light falls on rhodopsin, it causes isomerisation and splitting of rhodopsin into opsin and
all trans retinal. This photolysis of rhodopsin initiates vision signal from rod cells.
The all trans retinal formed is inactive. It is reduced to all trans retinol by the enzyme
Retinene reductase and NADPH. The all trans retinol enters into blood stream and in liver it
is isomerized to 11-cis retinol by the enzyme Retinol isomerase.
The 11-cis retinol from blood stream enters in to retina of eye where it is oxidized to 11-cis
retinal by the enzyme Retinene reductase and NAD+. The 11-cis retinal combines with
protein opsin to form rhodopsin. Thus the cycle is repeated to help normal dim light vision.

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

Vitamin D:
Synonyms: Antirachetic factor, calciferol
Dietary sources: Richest source of vitamin D include liver oils of fishes like cod fish, halibut, eggs,
cheese, etc.
Chemistry: Vitamin D is a group of closely related steroids (D1 to D5) of which Vitamin D2 and D3 are
physiologically active. 7-dehydrocalciferol in animals (skin) and ergosterol in plants are pro-
vitamins of vitamin D3 and D2 respectively which produce the vitamins on exposure to UV
light.
H3C CH3
H3C CH3
CH3 CH3
CH3 CH3

CH2 CH2

Ergocalciferol (Vitamin D 3)
Cholecalciferol (Vitamin D 2)
HO HO

Biological role:
1. Vitamin D plays important role in intestinal absorption of calcium and phosphate ions.
2. It promotes mineralisation of bone and helps in growth and development of bones.
3. It plays important role in citrate metabolism in body.
4. It increases renal excretion of phosphate ions.
5. It increases activity of Phytase enzyme in intestine.
Deficiency disorders: Deficiency of vitamin D in children leads to rickets and osteomalacia in adult.
Rickets: Rickets is a disorder of deficiency of vitamin D in children. It is characterized by bow legs,
knock knee, swollen joints and a pigeon breast appearance. It is due to decreased
calcification of growing bones. It may also be due to calcium deficiency. For treatment of
Rickets external supplementation of vitamin D and calcium compounds is done.
Osteomalacia: Osteomalacia is a disorder of deficiency of vitamin D in adult. It is characterized by
softening and deformation of bones of pelvic girdle, ribs and femora. It is painful condition

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

generally found in women during pregnancy and lactation. For treatment of Osteomalacia
vitamin D and calcium compounds are given as external supplements.
Vitamin E:
Synonyms: Antisterility factor
Dietary sources: Good dietary source of vitamin E include eggs, milk, meat, corn oil, liver, fish etc.
Chemistry: Vitamin E refers to a group of isoprenoid substituted 6 hydroxy chroman derivatives
called tocopherols. Four tocopherols ie α, β, γ and δ have been isolated of which α
tocopherol is the most abundant and potent tocopherol present in nature.
CH3
CH3 CH3 CH3 CH3
H3C O
(CH 2)3 CH (CH 2)3 CH (CH 2)3 CH CH3

HO
a Tocopherol
CH3

Biological role:
1. Vitamin E acts as natural antioxidant in body. It is the first line of defence against
peroxidation of polyunsaturated fatty acids present in phospholipids of cellular and
subcellular membranes.
2. Vitamin E and selenium act synergistically and reduce each others requirement in body.
3. Vitamin E prevents hepatic necrosis produced by lack of sulphur containing amino acids in
dietary proteins.
4. It acts as a co factor in electron transport system between cytochrome B and C.
Deficiency disorders: Daily dietary requirement of vitamin E is 25 to 30 mg. Inadequate supply of
vitamin E or malnutrition lead to deficiency of vitamin E. Deficiency of vitamin E causes;
 Muscle weakness
 Muscular dystrophy
 Fragility of erythrocytes
 Mild anemia
 Hepatic necrosis
 Neurological disorders
 Nocturnal muscle cramps
 Fibrocytic breast disease and
 Atherosclerosis
Vitamin K:
Synonym: Coagulation vitamin
Dietary sources: Green leafy vegetables like spinach, cabbage, cauliflower, and cereals are rich
sources of vitamin K. Animal foods like liver, milk, egg and fish also contain vitamin K. The
bacterial flora of intestine also produce vitamin K2.
Chemistry: Vitamin K refers to a group of naturally occurring naphthaquinones and their synthetic
analogues. Two natural naphthaquinones Phylloquinone called vitamin K1 and Menaquinone
called vitamin K2 have been isolated. A synthetic analogue menadione called vitamin K3 is
also used clinically.

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

O CH3 CH3

CH2 CH C CH2 (CH 2 CH2 CH CH 2)3 H

CH3 Phylloquinone (Vitamin K1 )

O
O
O CH3 CH3
CH3
CH2 (CH C CH 2)5 CH C CH3

CH3 Menaquinone (Vitamin K 2)

O
O Menadione (Vitamin K 3)

Biological role:
1. Vitamin K catalyses biosynthesis of prothrombin in liver.
2. It regulates biosynthesis of clotting factors VII, IX and X.
3. It reduces the prothrombin time
4. It is also involved in oxidative phosphorylation in animal tissues.
5. It is also involved in maintenance of normal levels of clotting factors II, VII, IX and X which
are synthesised as inactive precursors in liver.
Deficiency disorders: Pancreatic dysfunction, biliary diseases or intestinal disorders causing fat
malabsorption. Chemosterlization of bowel lead to deficiency of vitamin K.
Deficiency of vitamin K leads to lowering of prothrombin level and increase in clotting time
leading to hemorrhagic conditions. In newborns, deficiency of vitamin K causes hemorrhagic
diseases.
Thiamine (Vitamin B1)
Synonyms: Aneurine, Anti Beri Beri Factor
Dietary sources: Rice polishings, Wheat germ, cereals, pulses, milk, eggs and meat etc. are good
dietary sources of thiamin.
Chemistry: Thiamin is a water soluble, basic derivative of amino pyrimidine. It contains a
substituted amino pyrimidine ring linked to a substituted thiazole ring through a methylene
bridge.
NH2 CH3
-
Cl
+
N N CH 2CH 2OH
S
H3C N
Biological role:
1. Thiamine plays important role in normal growth and development of body.
2. It is essential for normal functioning of nerves.
3. The active form of Thiamin is thiamine pyrophosphate (TPP) which is a co enzyme of various
aldehyde transfer reactions.
4. TPP is involved in oxidative decarboxylation of certain important intermediates in
carbohydrate metabolism.
5. TPP acts as a coenzyme for Pyruvate dehydrogenase enzyme which converts pyruvic acid to
acetyl Coenztme A (Acetyl CoA)
6. TPP also acts as coenzyme for Transketolase enzyme in HMP shunt pathway.
Deficiency disorders: Daily dietary requirement of thiamin is between 1.2 to 1.7 mg for adults. It is

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

obtained from diet and also produced by the bacterial flora of intestine. Deficiency of
thiamine leads to Beri Beri.
Beri Beri: Beri Beri is a disorder of deficiency of thiamin. There are three types of Beri Beri.
1. Wet Beri Beri: It is characterized by edema of legs and face with anorexia and dyspepsia.
The calf muscles are tense, swollen and tender. there is palpitation and precordial pain and
there is decrease in volume of urine excreted.
2. Dry Beri Beri: The main characteristic of dry Beri Beri is polyneuropathy. The muscles
become weak and the person becomes unable to walk.
3. Infantile Beri Beri: It is acute and fatal thiamin deficiency state occuring in breast fed infants.
The symptoms are restlessness, excessive crying, puffiness and cyanosis and decreased
urine excretion. The infant generally dies within 24 to 48 hrs.
Riboflavin (Vitamin B2)
synonyms: Lactoflavin
Dietary sources: Milk, liver, kidney, hear, fish, cereals, roots and germinating barley are good
dietary sources of riboflavin.
Chemistry: Riboflavin is an isoxazoline derivative substituted with sugar alcohol ribitol. It occurs as a
water soluble yellow green pigment stable to heat but affected by light.
OH OH OH
H2C C C C CH 2OH
H H H
H3C N N O

NH
H3C N
O
Biological role:
1. It is involved in regulation of some hormones of carbohydrate metabolism.
2. In retina, it is involved in stimulation of optic nerve.
3. Active forms of riboflavin are Flavin Mono Neucleotide (FMN) and Flavin Adenine
Dinucleotide (FAD). They serve as prosthetic groups of oxidation reduction enzymes. FMN is
a constituent of cytochrome c reductasea and L amino acid dehydrogenase while FAD is
constituent of Xanthine oxidase, D amino acid dehydrogenase, glycine oxidase, acetyl CoA
dehydrogenase etc.
4. FMN and FAD serve as components of respiratory chain.
Deficiency disorders: Dietary requirement of riboflavin is 1.2 to 1.7mg daily in adults. Its deficiency
leads to following disorders.
 Angular stomatitis (Fissures at angles of mouth)
 Cheilosis (red epithelium at line of closure of lips)
 Glossitis (inflammation of toungue)
 Dyssebacia (appearance of enlarged follicles around the nose, plugged with dry sebacious
material
 scrotal dermatitis
 vascularization of cornea of eye causing lacrimation of photophobia.
Niacin (Vitamin B3))
Synonyms: Nicotinic acid, pellagra preventive factor
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Biochemistry and Clinical Pathology Vitamins and Coenzymes

Dietary sources: Niacin is abundantly present in nature. Rich sources of niacin are rice polishing,
yeast etc. milk, meat, eggs, tomato and green leafy vegetables also contain niacin.
Chemistry: Niacin is pyridine 3 - carboxylic acid. In tissues it occurs as its amide ie. nicotnamide.
COOH CONH 2

N N
Nicotinic acid Nicotinamide

Biological role:
1. The biologically active forms of niacin, ie. NIcotinamide Adenine Dinucleotide (NAD) and
NIcotinamide Adenine Dinucleotide Phosphate (NADP), act as coenzyme for several
Oxidoreductase enzymes.
2. NAD is a component of respiratory chain.
3. Niacin is involved in regulation of biosynthesis of cholesterol containing lipoproteins.
Deficiency disorders: Niacin requirement in adults is 10-20mg per day. Deficiency of niacin leads to
Pellagra.
Pellagra: Pellagra is a disorder of deficiency of niacin. It is characterized by;
Dermatitis: Skin of face shows erythema similar to severe sunburn. Skin of neck, face, knees
and breast shows thickening, roughening and dryness.
Diarrhea: The person passes watery stools with nausea and vomiting.
Dementia: forgetfulness with insomnia, depression, anxiety, headache etc.
Pyridoxine (Vitamin B6)
Dietary sources: Yeast and rice polishing are rich sources of pyridoxine. Milk, eggs, meat, liver and
green leafy vegetables also provide pyridoxine.
Chemistry: Vitamin B6 consists of three closely related naturally occurring pyridine derivatives and
their phosphates. They are pyridoxine, pyridoxal and pyridoxamine. They have equal vitamin
activity.
CH 2OH CHO CH 2NH 2
HO CH 2OH HO CH 2OH HO CH 2OH

H3C N H3C N H3C N

Pyridoxine Pyridoxal Pyridoxamine

Biological functions:
1. Pyridoxine is required for normal growth of infants.
2. It is important role in heme biosynthesis.
3. Active form of pyridoxine is pyridoxal phosphate which is the major coenzyme for activity of
Decarboxylase, Deaminase, Phosphorylase and Transulphurase enzymes.
4. It is required as conenzyme for the formation of neurotransmitters γ – amino butyric acid
(GABA) and serotonin in brain.
Deficiency disorders: Deficiency of pyridoxine leads to;
 Impaired growth
 Acrodynia (typical dermatitis)
 Edema of connective tissue layer of skin

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

 Convulsions
 Irritability
 Hypochromic microcytic anemia
Pantothenic acid (Vitamin B5)
Dietary sources: Pantothenic acid is abundantly present in yeast, liver, rice polishing, milk, eggs and
green leafy vegetables etc.
Chemistry: Pantothenic acid consists of β alanine and pantoic acid connected by a peptide bond.
O O OH CH3

HO C CH2 CH2 NH C CH C CH2OH

CH3
Pantothenic acid
Biological role:
1. Pantothenic acid is required for growth of infants.
2. It is a constituent of coenzyme A (CoA) which is required for;
a. Activation of acetyl to acetyl CoA
b. Formation of succinyl CoA in TCA cycle
c. Activation of fatty acids for their oxidation
d. For synthesis of fatty acids and cholesterol
Deficiency disorders: Deficiency of Pantothenic acid leads to;
 Inadequate growth
 Nausea and vomiting
 Certain gastro intestinal disorders
 Anemia
 Fatty liver
 Loss of hair
 Burning foot syndrome etc.
Folic acid (Vitamin Bc)
Synonyms: Folacin, Pteroyl glutamic acid
Dietary sources: Yeast, liver and leafy vegetables like cauliflower, milk and fruits are good dietary
sources of folic acid.
Chemistry: Folic acid consists of pteridine, para amino benzoic acid (PABA) and glutamic acid. In
liver it is present as pentaglutamate.
O COOH
CH
OH NH CH2
N H2C
N NH COOH

H3C N N Folic acid

Biological role:
1. Folic acid is essential for growth and cell division.
2. The active forms of folic acid, dihydro folic acid (DHF) and tetrahydro folic acid (THF) are
involved in transfer of single carbon moieties (formyl, formate, methyl, hydroxymethyl etc.).
3. It is involved in metabolism of histidine.
4. It plays important role in formation of;

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

a. methionine from homocystein.

b. serine from glycine
c. thymine from uracil
Deficiency disorders: Deficiency of folic acid leads to;
 Megaloblastic anemia
 Leucopenia
 Glossitis
 Gastrointstinal tract disorders
 Infertilty and inadequate lactation in females
Cyanocobalamine (Vitamin B12)
Synonyms: Antipernicious anaemia factor
Dietary sources: Liver, kidney, meat, fish and eggs are rich sources of cyanocobalamine.
Chemistry: Cyanocobalamine consists of a central portion made up of four reduced and extensively
substituted pyrrol rings connected through methylidine bridge. This central portion is called
corrin ring system.
A cobalt atom is present at the centre of the corrin ring system. Below the corrin ring system
there is a substituted benzimidazole riboside residue connected at one end to the central
cobalt atom and at the other end through riboside moiety to the side chain of corrin ring
system. A cyano group is coordinately bound to the central cobalt atom.
Biological role: The active form of cyanocobalamine is cobamide which acts as co enzyme in
isomerization of methyl malonyl CoA and in the combined conversion of homocystein to
methionine and methyl tetrahydrofolate to tetrahydrofolate. By this reaction stores of
methionine are maintained in the body and tetrahydrofolate is made available to participate
in purine and pyrimidine synthesis.
Deficiency disorders: Deficiency of Vitamin B121eads to Prenicious anaemia.
Biotin
Synonyms: Anti egg white injury factor
Dietary sources: Eggs, liver, kidney, yeast, milk, fruits and vegetables are good dietary sources of
biotin.
Chemistry: Biotin is sulphur containing imidazole derivative.
O

HN NH

(CH 2)4 COOH

S
Biotin

Biological role:
1. Biotin acts as co carboxylase.
2. It is required in the fixation of CO2 in the conversion of pyruvate to oxalo acetate, acetyl
CoA to malonyl CoA, propionate to succinate and in purine synthesis.
Deficiency disorders: Biotin deficiency leads to egg white injury.
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Biochemistry and Clinical Pathology Vitamins and Coenzymes

Egg white injury: Consumption of raw egg causes deficiency of biotin. Egg white contains a protein
Avidin which combines very tightly with biotin and prevents its absorption. The symptoms of
egg white injury are;
 Retarded growth
 Loss of hair
 Depression
 Hallucination
 Muscle pain
 Dermatitis etc.
Lipoic acid
Synonyms: Thioctic acid
Dietary sources: Lipoic acid is widely distributed in natural foods.
Chemistry: Lipoic acid is a water soluble sulphur containing fatty acid. Chemically, it is 6, 8 dithio
octanoic acid. It exists in oxidized and reduced forms.

Biological role: Lipoic acid acts as coenzyme in oxidative decarboxylation of α keto acids like
pyruvate and α keto glutarate.
Deficiency disorders: No deficiency symptoms have been established for lipoic acid.
Vitamin C
Synonyms: L - Ascorbic acid, Antiscorbutic agent
Dietary sources: Amla is the richest source of vitamin C while citrous fruits, tomato, lemon, adrenal
cortex etc. are also rich in vitamin C. grapes, apple, banana and green leafy vegetables also
provide vitamin C.
Chemistry: Ascorbic acid is an enediol lactone resembling hexose sugar L-gulose. It is a strong
reducing agent and readily gets oxidized to dehydro ascorbic acid (ascorbone). Both the
reduced and oxidized forms are biologically active. On heating (cooking) it gets
decomposed.
OH OH
O O
O HC CH 2OH O HC CH 2OH

HO OH O O

Ascorbic acid Dehydro ascorbic acid

Biological role:
1. Ascorbic acid is a strong reducing agent. It is involved in biochemical oxidation reduction
reactions of cells.
2. It is involved in biosynthesis of hydroxyproline from proline. Hydroxy proline is an important
amino acid of collagen.
3. In adrenal cortex, it is involved in hydroxylation of steroids.

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Biochemistry and Clinical Pathology Vitamins and Coenzymes

4. It is also involved in biosynthesis of bile salts.

5. It is also involved in metabolism of tyrosine, phenylalanine and tryptophan.
6. It is also involved in conversion of folic acid to folinic acid.
7. It plays important role in absorption and mobilisation of iron.
8. It plays important role in maintaining normal intracellular material of cartilage, dentine and
bone.
Deficiency disorders: Daily dietary requirement of ascorbic acid is 50 – 70 mg. Prolonged deficiency
of ascorbic acid leads to scurvy.
Scurvy: Scurvy is a deficiency disorder of vitamin C. Daily dietary requirement of ascorbic acid is 50–
70 mg. Prolonged deficiency of ascorbic acid leads to scurvy. Scurvy is characterised by;
 Internal hemorrhage
 Swelling, sponginess, tenderness and bleeding of gums
 Loosening of teeth
 Poor healing of wounds
 Swelling of ends of long bones and pain on movement
 Easy fracturability of bones
 Anemia
 Susceptibility to infection
 General weakness.

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