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Water Soluble Vitamins
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Objectives: by reading this topic; the student would be able to:
1. Define vitamins and illustrate vitamin classification.
2. Describe the structure, dietary sources, and metabolism of water soluble
vitamins.
3. Identify the biochemical role of different water soluble vitamins.
4. Correlate deficiency in vitamin levels with clinical conditions.
LECTURE 1
Vitamins are group of complex organic compounds present in very small
quantities in food and absorbed into the body during digestion. The name
vitamin is obtained from "vital amines“. They are not synthesized in the body
except Vitamin K.
Vitamins can perform their work in very small quantities. Hence, the total daily
requirement is usually very small.
FUNCTIONS OF VITAMINS
 Vitamins help to keep good Health.
 Vitamins are required for metabolism and they create metabolically active
enzymes which are very essential for various functions of our body.
 Vitamins are very important the proper growth
 Ensuring protection against the viruses.
CLASSIFICATION OF VITAMINS
1. Fat-soluble vitamins
 They are soluble in fat and
 They are absorbed by the body from the intestinal tract.
 They are stored in the body's fatty tissue ± Liver.
 The four fat-soluble vitamins are A, D, E, and K.
2. Water-soluble vitamins
 Water-soluble vitamins – vitamin C and vitamin B Complex.
 Any leftover water-soluble vitamins leave the body through urine.
 Vitamin B12 is the only water-soluble vitamin that can be stored in the liver
for many years.
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Water Soluble Vitamins
VITAMIN
B Group
 Introduction:
 In general B complex group have well defined Coenzyme functions in the
cellular metabolism.
 They include: Thiamine (B1), Riboflavin (B2), Niacin, Pantothenic acid,
Pyridoxine (B6), Biotin, Folic acid, and Cobalamine (B12).
 Sources: there are some general sources for all B complex group including:
germinating seeds, wheat germ, beans, yeast, liver, egg yolk, milk,
vegetables, fish, honey, and meat.
 These vitamins present in food and are readily absorbed in GIT, usually
there is no appreciable storage, the excess is excreted in urine after
metabolism.
 Washing before cooking and draining the water after cooking will result in
loss of much of the water soluble vitamins.
1. Thiamine (B1):
 Structure:
 It is a basic substance contains a pyrimidine ring linked to a thiazole ring. It
is fairly stable in acid solutions but is rapidly destroyed in alkaline medium.

OH of the hydroxyethyl group in the thiazole can be esterified with 2
molecules of phosphoric acid to form Thiamine pyrophosphate (TPP)
which is the active coenzyme form of the vitamin.
 Metabolism:
 Free thiamine is readily absorbed by the small intestine. It is phosphorylated
mainly in the liver to form TPP.
 There is no storage of B1 vitamin so regular supplies are needed in the diet.
 Functions:
 TPP acts as a coenzyme in the following reactions:
1. Oxidative decarboxylation reactions, Mg++ ions are required for the
activation; as in d carboxylation odf α-ketoglutaric acid.
2. Transketolation reactions; in hexose-mono-phosphate shunt pathway of
glucose metabolism.
3. Oxidative decarboxylation of branched chain amino acids, like valine,
leucine, and isoleucine; Flavin-Adenine-dinucleotide (FAD),
niacinamide-adenine-dinucleotide (NAD), and Mg++ are also required for
the reaction.
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 RDA: 1.5 mg/day.
Recommended Dietary allowance (RDA) is the level of intake of
essential nutrients sufficient to meet the nutritional needs of healthy
individuals in general population
 Clinical correlations:
 Deficiency: this will result in a condition called beri-beri which has
two components:
1. Cardiovascular failure: enlargement of the heart and edema.
2. Neural component: peripheral neuritis.
 Re-feeding syndrome: this potentially lethal condition is defined as
severe electrolyte and fluid shifts associated with metabolic
abnormalities in malnourished patients undergoing re-feeding
whether this is oral, enteral, or parenteral. It is associated with B1
deficiency which should be corrected and given to the patient before
re-feeding is started and also the calorie repletion should be slow.
Factors that increase the risk of re-feeding syndrome include:
marasmus, chronic alcoholism, cancer treatment, prolonged fasting,
and surgery.
2. Riboflavin (B2):
 Structure: it is derived from isoalloxazine ring combined with ribityl
alcoholic group; which can be esterified with phosphoric acid to form
Flavin-Mononucleotide (FMN). It may be linked to adenine nucleotide
through a pyrophosphate linkage to form Flavine-Adenine-Dinucleotide
(FAD).
FMN and FAD are the two Coenzyme forms of the vitamin
 Functions:
 FMN & FAD are involved in hydrogen transfer reactions as follows:
1. FMN is a coenzyme for the enzymes cytochrome C reductase and Lamino acid oxidase.
2. FAD is a coenzyme for the enzymes Xanthine oxidase, D-amino acid
oxidase and succinate dehydrogenase.
 RDA: 1.5-2 mg/day.
 Clinical correlation:
 Deficiency: Lesions of the lips, fissures at angles of the mouth
(cheilosis), dermatitis of the face, glossitis (red tongue), and
vascularization of the conjunctiva and the cornea occurs.
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LECTURE 2
3. Niacin:
(Synonyms: P-P-factor=Pellagra Preventing factor, Nicotinic acid)
 Structure: Niacin is pyridine-3-carboxylic acid. Its biologically active
forms are:
1. Niacinamide–Adenine-Dinucleotide (NAD).
2. Niacinamide–Adenine-Dinucleotide (NADP): the phosphorylated
form of NAD.
 Sources:
 In addition to general sources of B complex vitamins; niacin can be
synthesized from the essential amino acid Tryptophan.
 Functions:
 NAD & NADP function as coenzymes for hydrogen transfer enzymes
(dehydrogenases) as follows:
1. NAD is a coenzyme for the enzymes Alcohole dehydrogenase and Lactic
acid dehydrogenase.
2. NADP is a coenzyme for the enzymes Glucose-6-phosphate
dehydrogenase.
3. Both NAD & NADP are coenzymes for the enzyme Glutamic acid
dehydrogenase.
 RDA: 20 mg/day
 Clinical correlation:
 Deficiency: causes a disease called Pellagra (pelle=skin; Agra=rough)
characterized by: dermatitis, diarrhea, and dementia (3'D's) and if not
treated the 4th 'D' death follows. The dermatitis involves areas exposed to
sun or pressure, in addition to loss of appetite, vomiting, stomatitis,
soreness of the tongue, and mental depression.
Niacin has a pharmacological action on decreasing plasma lipids;
therefore niacin is used in the treatment of hyperlipidemia
4. Pyridoxine (B6):
 Structure: it has three related compounds: Pyridoxine occur mainly in plants;
Pyridoxal and pyridoxamine which are present in animal products. Its active
form is Pyridoxal Phosphate which can combine to NH3 group to form
Pyridoxamine Phosphate.
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 Functions:
1. Coenzyme for Transaminases: B6 importance in amino acid metabolism
depends on its ability to take up NH3 reversibly to form pyridoxamine
phosphate.
2. Coenzyme for non-oxidative decarboxylases:
3,4-di ydroxyp nylalanin →Dppamin + CO2
Glutamic acid →Gamma aminobutyric acid (GABA) + CO2
yrosin → yramin + CO2
3. Conversion of tryptophan to niacin.
4. Interconversion of glycine and serine: where it works along with folic
acid.
5. Trans-sulphuration reactions
Homocysti n +s rin → omos rin +cyst in
6. Synthesis of sphyngosine from serine and arachidonic acid from linoleic
acid.
7. Transport of amino acids. Across cell membranes.
 RDA: 2 mg/day
 Clinical correlations:
Deficiency:
 This may result in a hypochromic microcytic anemia because the
vitamine is required at one-stage-decarboxylation- in heme synthesis.
 Homocystinuria and cystathioninuria occur in B6 deficiency due to
impaired metabolism of methionine.
Pharmacological Facts of B6:
1. Treatment with isonicotinic acid hydrazide (INH) patients with tuberculosis induces a B6
deficiency manifested by neuropathy and excretion of abnormal metabolites of tryptophan
in urine. Large doses of B6 will overcome this condition.
2. B6 is found to be of value in treatment of nausea and vomiting during pregnancy
(morning sickness),
5. Pantothenic acid (B3):
(Synonyms: Pantothenic in Greek =from everywhere)
 Structure: it is a pseudopeptide formed by combination of a butyric acid
d rivativ wit β–alanine.
 Functions: it is a component of a very important coenzyme called
Coenzyme A (HS-CoA) which has the following functions:
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1. Formation of acetyl-CoA and fatty acyl-CoA.
2. Formation of acyl-carrier protein required for synthesis of fatty acids.
3. Acetyl-CoA is the starting point for citric acid cycle and fatty acid
biosynthesis.
4. Adrenal cortical function since acetyl CoA is required for steroid ring
synthesis.
5. Succinyl-CoA is a component of citric acid cycle.
6. Fatty acyl-CoA formation point for the oxidation of fatty acid or for their
incorporation into triglycerides or phospholipids.
 RDA: 5-15 mg/day
 Clinical correlation:
 Deficiency: due to the widespread of this vitamin, its deficiency is very
rare.
6. Biotin (Vitamin H):
 Structure: It is a heterocyclic compound containing sulphur.
 Sources:
 In addition to general sources of B complex vitamins; large amounts of
this vitamin are synthesized by intestinal flora, but this source of supply is
lost during therapy with sulphonamides and antibiotics. Avidin is a basic
protein in egg white which is capable of forming an unabsorbable
complex with biotin thus also depriving the availability of the vitamin.
 Functions: it is a coenzyme in CO2 transfer reactions (or CO2 fixation)
involved in gluconeogenesis, lipogenesis, and fatty acid synthesis:
1. Acetyl-CoA to Malonyl-CoA.
2. Pyruvate to oxalacetate.
3. Propionyl-CoA to methylmalonyl-CoA.
 RDA: 100-300 µg/day
 Clinical correlation:
 Deficiency: this is very rare leading to alopecia, gastrointestinal and
nervous symptoms.
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LECTURE 3
7. Folic acid:
 Structure: The term folic acid is derived from its widespread presence in
green leafy vegetables (folium=leaf). The major parts of folic acid are:
1. Pteridine nucleus.
2. Para aminobenzoic acid (PABA).
3. Glutamic acid.
 All three parts form Pteroylglutamic acid (PGA). The reduced form of
the vitamin (by addition of 4 hydrogens to the pteridine moiety), will
make Tetrahydrofolic acid which is the active form of the vitamin.
 Sources:
 In addition to general sources of B complex vitamins; folic acid is found
in green leafy vegetables.
 Many microorganisms can synthesize folic acid from PABA including
those inhabiting the intestinal tract.
 Functions:
 Formation of the active form of Folic acid (Tetrahydrofolic acid) is
brought about by a folic acid reductase enzyme which requires NADPH
and Ascorbic acid as coenzymes.
 The tetrahydrofolaic acid can reversibly combine with a carbon unit at N5
or N10; and this is the basis of its function.
 The one carbon moiety can be derived from several sources and be
utilized to form several compounds; as follows:
1. One carbon moiety donors: like methyl group of methionine or
thymine.
2. One carbon moiety acceptors: as in homocysteine or uracil to form
methionine.
Folate Cycle
Tetrahydrofolate takes up a one carbon moiety (-CH3) at N5 position. The
methyl group is transferred to cobalamine which helps methylation of
homocysteine to form methionine. The folate is returned to the folate pool to
further take part in one carbon transfer reactions. Otherwise, folate remains
trapped with the methyl group and its further functioning is impaired. This
close correlation of folic acid and B12 is called the "Folate Cycle".
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 RDA: 100 mg/day
 Clinical correlation:
Deficiency:
 Since the vitamin is very much involved in the synthesis of purine ring
which is a component of nucleic acids, and methylation of the
pyrimidine ring to form thymine, a constituent of DNA, the most
affected function will be cell multiplication.
 The hemopoietic system will be the earliest to be involved because it
shows the maximum of cell division and multiplication normally.
 Macrocytic anemia, leucopenia and neurological symptoms are
produced.
 In pregnancy there is increased requirement for folic acid by both;
the mother (to prevent anemia) and the fetus (to prevent neural tube
defect); therefore it is given prophylacticly to all pregnant women.
Pharmacological facts of Folic acid:
 Sulfonamide drugs and antibiotics inhibit bacterial growth by blocking
the incorporation of PABA in the folic acid synthesis (competitive
inhibition).
 Trimethoprim inhibits the enzymatic conversion of dihydrofolate to
tetrahydrofolate by bacteria thus inhibiting its growth.
 Methotrexate antagonizes folic acid thus inhibits cell division and
multiplication as in treating leukemia and malignancy.
8. Vitamin B12 (Cobalamin):
 Structure: B12 molecule is composed of:
1. Corrin ring system with four pyrrole rings.
2. Trivalent cobalt atom.
3. Cyanide and azole ring of a nucleotide.
 Metabolism:
 The vitamin is absorbed from the intestine only in the presence of
Intrinsic factor. Which a protein secreted from cells of the gastric
mucosa.
 The
active
forms
of
B12
are
methylcobalamin
and
deoxyadenosylcobalamin.
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Water Soluble Vitamins
Facts of B12:
 Intrinsic factor from gastric juice is necessary for absorption of vitamin B12.
 B12 is transported in plasma bound to specific carrier proteins called
Transcorrin I and Transcorrin II.
 Functions:
 The vitamin functions as coenzyme after combining with an adinosyl
moiety which replaces the –CN group. The pentose of the adenosine
moiety is deoxyribose, and the coenzyme is called (Cobamide
Coenzyme); which is involved in the following reactions:
1- Methyl-Malonyl-CoA to Succinyl CoA.
2- Methylation of homocysteine to methionine and the methylation of
pyrimidine ring to form thymine.
3- Metabolism of diols; ex. Ethylene glycol.
4- Ribonucleotides to deoxyribonucleotides.
 RDA: 5 µg/day
 Clinical correlation:
Deficiency:
 Like folic acid, B12 is also intimately connected to hemopoiesis; thus its
deficiency leads to Macrocytic anemia.
 Sub-acute combined degeneration: Lesions in CNS along with
anemia.
 Pernicious anemia: caused by deficiency of the Intrinsic factor
associated with absence of HCL (Achlorhydria) and enzymes (Achylia)
in gastric juice.
VITAMIN C
Group
 Structure:
 It is a white crystalline substance with a very acidic taste.
 It is a strong reducing substance.
 It is stable in the solid form and in acidic solutions, but is rapidly
destroyed in alkaline solutions.
 Sources: Fresh green leafy vegetables and salad vegetables like cabbage,
lettuce, spinach, and cucumber contain this vitamin. In addition to citrus
fruits (lemons & oranges) and melons.
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 Functions: The vitamin is intimately concerned with the metabolism of
mesenchymal tissues, osteoid, dentine, and collagen.
1- Maintenance of redox potential in the cell: vitamin C plays a role of
a coenzyme in hydrogen transfer reactions involving NADP and
glutathione.
2- Collagen synthesis: hydroxyproline is an important amino acid in
collagen; vitamin C is required for its synthesis from proline in
connective tissue.
3- Tyrosine metabolism: its conversion catecholamines by dopamine-βhydrolase.
4- Absorption of iron from GIT: by converting inorganic ferric iron to
the ferrous form.
 RDA: 70 mg/day
 Clinical correlation:
Deficiency (Scurvy)
 It is failure to deposit intercellular cement substance.
 The capillaries become fragile and there is a tendency to hemorrhage.
 Wound healing is delayed due to deficiency in the formation of
collagen.
 There is poor dentine formation in children leading to poor teeth
formation.
 Gums are spongy swollen and bleed on slightest pressure.
 Osteoid of the bone is poorly laid and mineralization is inadequate.
 References:

Lippincott's Illustrated Review in Biochemistry by Richard Harvey and Denise Ferrier; 5 th
edition 2010. Unit 5, Chapters 28.

Textbook of Biochemistry by Dr A V S S Rama Rao; 11th edition 2010. Chapter 11.

Clinical chemistry & Metabolic medicine by Martin A. Crook; 7th edition 2008. Chapter 15.

Clinical Chemistry by Michael L. Bishop and colleagues; 4th edition 2005. Part IV, chapter 31.

Clinical Chemistry by William J Marshall & Stephen K Bangert; 6th edition 2008. Chapter 20.
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