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Water Soluble Vitamins

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Objectives:

by reading this topic; the student would be able to:

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 B

is the only water-soluble vitamin that can be stored in the liver

for many years.

Define vitamins and illustrate vitamin classification.

Describe the structure, dietary sources, and metabolism of water soluble
vitamins.

Identify the biochemical role of different water soluble vitamins.

Correlate deficiency in vitamin levels with clinical conditions.

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VITAMIN

Group

 Introduction:

 In general B complex group have well defined Coenzyme functions in the

cellular metabolism.

 They include: Thiamine (B

), Riboflavin (B

), Niacin, Pantothenic acid,

Pyridoxine (B

), Biotin, Folic acid, and Cobalamine (B

 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 (B

 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 B

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.

 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  B

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 (B

 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).

 Functions:

 FMN & FAD are involved in hydrogen transfer reactions as follows:

1. FMN is a coenzyme for the enzymes cytochrome C reductase and L-

amino 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.

FMN and FAD are the two Coenzyme forms of the vitamin

Recommended Dietary allowance (RDA) is the level of intake of
essential nutrients sufficient to meet the nutritional needs of healthy
individuals in general population

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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 4

'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.

4. Pyridoxine (B

 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.

Niacin has a pharmacological action on decreasing plasma lipids;

therefore niacin is used in the treatment of hyperlipidemia

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 Functions:

1. Coenzyme for Transaminases: B

importance in amino acid metabolism

depends on its ability to take up NH

reversibly to form pyridoxamine

phosphate.

2. Coenzyme for non-oxidative decarboxylases:
3,4-di ydroxyp nylalanin →Dppamin + CO

Glutamic acid →Gamma aminobutyric acid (GABA) + CO

yrosin → yramin + CO

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 B

deficiency due to

impaired metabolism of methionine.

5. Pantothenic acid (B

(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:

Pharmacological Facts of B

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 B

will overcome this condition.

2. B

is found to be of value in treatment of nausea and vomiting during pregnancy

(morning sickness),

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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 CO

transfer reactions (or CO

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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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 N

or N

; 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 B

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.

8. Vitamin B

(Cobalamin):

 Structure: B

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

are

methylcobalamin

and

deoxyadenosylcobalamin.

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.

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 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, B

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.

 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.

Facts of B

 Intrinsic factor from gastric juice is necessary for absorption of vitamin B

 B

is transported in plasma bound to specific carrier proteins called

Transcorrin I and Transcorrin II.

VITAMIN

Group

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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-β-

hydrolase.

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

edition 2010. Unit 5, Chapters 28.

 Textbook of Biochemistry by Dr A V S S Rama Rao; 11

edition 2010. Chapter 11.

 Clinical chemistry & Metabolic medicine by Martin A. Crook; 7

edition 2008. Chapter 15.

 Clinical Chemistry by Michael L. Bishop and colleagues; 4

edition 2005. Part IV, chapter 31.

 Clinical Chemistry by William J Marshall & Stephen K Bangert; 6

edition 2008. Chapter 20.