Biochemistry-1

2nd level Students-Pharm D

Lecture 2: Vitamin Chemistry

By: Dr. Salma M. Eraky
Assistant Professor of Biochemistry
Vitamins
 5. Pyridoxine (vit. B6)
rat antidermatitis factor

Vitamin B6 is a collective term for pyridoxine, pyridoxal and pyridoxamine, all

derivatives of pyridine.
These derivatives differ only in the nature of the functional group attached to
the ring.
All these derivatives serve as a precursor for the biologically active coenzyme,
pyridoxal phosphate (pyr.p)
 5. Pyridoxine (vit. B6)
rat antidermatitis factor

Sources:
Good sources of the vitamin are wheat, corn, egg yolk, liver and muscle meats. Royal
Jelly of bees is very rich in vitamin B6.
 Functions of pyr.p

Pyr.P acts as a coenzyme for a large number of enzymes that catalyze reactions
involving amino acids as:
1. transamination
2. Deamination
3. Decarboxylation
4. Condensation
5. Desulfuration
6. Transsulfuration
7. Niacin synthesis from Tryptophan
 1. Transamination (co-enzyme with
transaminases):
• Transaminases: transfers the amino group from an amino acid to an α-keto acid to
form a new amino acid and a new -keto acid.

1. Alanine Transaminase (ALT) is also called glutamate pyruvate aminotransferase

(GPT).
2. Aspartate Transaminase (AST) is also called glutamate oxaloacetate
aminotransferase (GOT).
 2.Deamination (co-enzyme for deaminase)
• removal of amino group of certain amino acids
• Amino acid converted to ???

Enzyme
Co-enzyme
• Ex:
Serine Pyruvate +NH3
 3. Decarboxylation of amino acids

• Removal of CO2 of certain amino acids

Enzyme
coenzyme
1. DOPA Dopamine (synthesis of adrenaline

Enzyme
coenzyme
2.Glutamic -amino butyric acid (GABA) (necessary for metabolism in
brain).
 4. Condensation
Pyr.p
Glycine + Succinyl CoA -Amino levulinic acid Hb

5. Desulfuration
• removal of sulfur of cysteine

6. Trans-sulfuration

• Homocysteine + serine homoserine + cysteine

Trans-
sulfurase/pyr
.p

7. Niacin synthesis from Tryptophan (co-enzyme with Kynureninase)

 Pyridoxine (vit B6) Deficiency
1.Impaired growth, due to disturbed amino acid metabolism

2.Anemia, due to decreased synthesis of Hb

3.Convulsions (in infants) due to decreased GABA (-Aminobutyrate) in brain

4.Pellagra, since it is required for niacin synthesis

5.Nausea & vomiting in early pregnancy as a result of depletion of vit. B6 due to its excessive

use in amino acid metabolism to synthesize the new proteins of the embryo.

6.In Rats, lead to Dermatitis (Anti–Dermatitis Factor)

 6. Biotin (Vit H, B7) coenzyme R
Chemistry
• Biotin is a heterocyclic sulfur-containing monocarboxylic acid.

• Biotin is present in nature in combination with lysine forming biocytin which is active
and acts as a coenzyme.
 Distribution

• Biotin is present in almost all foods, particularly liver, milk, egg yolk and yeast. Large
amounts are present in royal jelly of bees

Raw egg-white and biotin deficiency

•Raw egg white contains a protein known as avidin which binds to biotin and inhibits its
absorption from intestine.
 Biotin Functions
• Biotin is an essential component of enzymes that catalyze the incorporation of
CO2 into metabolites i.e. enzymes involved in the carboxylation reactions
(carboxylases).
Carboxylase/Biotin Krebs cycle
Pyruvic acid Mn+2 / ATP Oxaloacetate Gluconeogenesis

Carboxylase/Biotin
Acetyl CoA Mn+2 /ATP
Malonyl CoA Fatty acid synthesis

Carboxylase/Biotin Odd chain fatty acid oxidation

Propionyl CoA Methylmalonyl CoA
Mn+2 /ATP
 7. Folic acid (Vit. B9)
Chemistry
1- Pteridine ring
2- PABA
3- Glutamic acid
• No requirements, because it can be formed by bacteria of large intestine.
• Sometimes, pregnant or lactating women may require folic acid supplementation.
• In the case of inadequate absorption due to alcoholism, a commercial folic acid may be administered .
 7. Folic acid (Vit. B9)

2NADPH+ 2H+ Dihydrofolate reductase

2NADP
Vit. C

6
7
8
Active form= THFA=Tetra Hydro folic acid=Folinic acid
 Function of Folinic Acid (THFA)
• THF is the coenzyme required for the transfer of such a single carbon units (One
Carbon fragment metabolism) as
• Formyl (CHO)
• Formate (HCOOH)
• Methyl (CH3)
• Hydroxy methyl group (CH2OH).
 • Utilization of single-carbon moiety

1- Source of carbon 2 and 8 of purines in nucleic acid synthesis.

2- Synthesis of amino acids. Examples:

A- It supplies the -carbon of serine.
B- The methyl group is used for transmethylation reactions with the help of Vit B12
in regenration of Methionine from Homocysteine:
 Deficiency of Folic Acid

1. Megaloblastic anemia which is a category of macrocytic anemia, caused by diminished

synthesis of purines and thymidine leading to an inability of cells to make DNA and
hence RBCs.
2. Leucopenia (as it is used for synthesis of white blood cells).
3. Poor growth
4. Birth defects (neural tube defect).
Deficiency of Folic Acid
8. Vitamin B12, Antipernicious Anemia Factor
(cyanocobalamine)
• Cobalamine is formed of Corrin ring system that differ from the Porphyrin ring (enter in structure of Hb)
in that two of the pyrrole rings are linked directly rather than through a methylene bridge.
• Cobalt is held in the center of the corrin ring by 4 coordination bonds from
the nitrogens of the pyrrole groups.

• The remaining coordination bonds of the cobalt are with the nitrogen of 5,6
dimethyl benzimidazole and with cyanide in commercial preparation of the
vitamin in the form of cyanocobalamine.
 Forms of vitamin B12

1- Synthetic form: Cyanocobalamin

2- Natural forms:
A- Hydroxycobalamin B- Methylcobalamin
C- Adenosylcobalamin
Forms of vitamin B12
 Distribution

• it is not present in plants

• Animals obtain the vitamin performed by their natural bacterial flora or by eating food
derived from other animals such as liver, whole milk, egg and chicken.
 Absorption:

• Parietal cells of stomach secrete a glycoprotein called intrinsic factor (IF).

• Intrinsic factor binds to cobalamin (Extrinsic factor) to form cobalamin–intrinsic
factor complex absorbed by special receptor site on the surface of mucosal cells of
the ileum.
• The bound cobalamine is transported into the mucosal cell and subsequently into
the general circulation, where it is carried by vit B12 binding protein
(transcobolamin II).
• Lack of intrinsic factor prevents the absorption of Vit. B12, resulting in pernicious
anemia.
 Metabolic Function of Vit B12 :

1- Regeneration of Methionine from Homocysteine requires 5-methyl THF with the

help of Vit B12 (in form of methylcobolamine)

2-Rearrangement of Methylmalonyl CoA into Succinyl CoA requires coenzyme Vit

B12 along with THFA
 Methylmalonyl CoA arises during
• Degradation of some amino acids
• Oxidation of odd chain fatty acids.
Metabolic Function of Vit B12 :

Heme synthesis
 Deficiency of Vit B12
1. Megaloblastic anemia (Due to deficiency of purine & thymine synthesis)
2. Pernicious anemia which is characterized by: macrocytic anemia and
nervous manifestations.
• When B12 is deficient, abnormal fatty acid
accumulates and become incorporated into cell
membranes, including those of the nervous system.
• This may account for some of the neurologic manifestations of Vit B12
deficiency.
 Deficiency of Vit B12

• In contrast to other water-soluble vitamins, significant amount (4 to 5 mg) of

vitamin B12 is stored in the body.
• It may take several years for clinical symptoms of Vit. B12 deficiency to develop in
individuals who have had a partial or total gastrectomy (Remember IF and B12
absorption)
• Cobalamine deficiency may lead to a deficiency of THF forms needed in purine and
thymine synthesis (needed for DNA replication), resulting in the symptoms of
megaloblastic anemia (How??)

N5-methyl THF not used efficiently

Vit B12 deficiency
N5-methyl THF accumulates

Deficiency of other forms of THF needed for purine and thymine Megaloblastic Anemia
synthesis
 vitamin C or L-ascorbic acid

Chemistry:
•It is an endiol-lactone of an acid
•contains a double bond between C2 and C3, 2 hydroxyl groups at C2 and C3
and lactone ring between C1 and C4.
•It is an example of sugar acid.
•It is a strong reducing agent due to easily liberation of 2 hydrogens
from the hydroxyl groups at C2 and C3, so it is oxidized to
dehydroascorbic acid.
Distribution of vitamin C
Citrus fruits, potatoes, tomatoes, the green vegetables
are good sources of vitamin C.

Metabolism
 No synthesis in human but synthesis occurs from D-glucose in certain animals
e.g., rat.
 Catabolism occurs by L-ascorbic acid oxidase to oxalic and L-threonic acids.
 Functions of vit C
1- Vitamin C is vital for production of collagen
• Collagen enters in the formation of:
• Connective tissues [Fibroblasts (Collagen)],
• Teeth [Odontoblasts (Dentin of teeth)]
• Bone [Osteoblasts (Osteoid tissue)]
• Intercellular cement substances of capillaries.
That is why vitamin C accelerates the healing of wounds and fractures of
bones.
Role of vit C in collagen formation:
vitamin C accelerates the hydroxylation of proline and lysine amino acids into
hydroxyproline and hydroxylysine respectively, which are required in the synthesis of
collagen (Post translational modification)
 N.B:
1- Hydroxylation allows the collagen
molecule to assume its triple helix
structure, provides extra capacity of
H-Bonding
2- Prevents denaturation of collagen
fiber in temperature changes.
2-
Vit C is necessary with [Dihydrofolate reductase]
for the activation of folic acid (member of Vit. B-complex) into folinic acid
(active form).

3- Vit. C helps the absorption of iron as it helps the reduction of ferric ions to
ferrous ions

4- Prevention of chronic disease: It works as antioxidant such as Vit. E and Vit. A

5- Vit C is required for tryptophan and tyrosine metabolism

Vit C
Vit C required for metabolism of tyrosine when large quantities of tyrosine is ingested.
• High intake of tyrosine leads to the formation of large quantities of P-hydroxy phenyl
pyruvic acid which inhibits P-hydroxy phenyl pyruvic acid hydroxylase.
• Vit. C prevents this inhibition and so protects the enzyme.
 Deficiency of vitamin C

Deficiency of Vit C causes Scurvy

The symptoms of Scurvy:

anaemia
Loss of appetite
fragile blood
spongy gums, due to haemorrhage loss of weight .
vessels
loose teeth from gum
delayed healing of
wounds.
 Nutritional anemias
Anemia is a condition in which the blood has a lower than normal concentration of hemoglobin, which results in a
reduced ability to transport oxygen. Nutritional anemias (that is, those caused by inadequate intake of one or more
essential nutrients) can be classified according to the size of the red blood cells (RBCs) or mean corpuscular volume
(MCV) observed in the individual.
• Microcytic anemia (MCV below normal),
caused by lack of iron, is the most common
form of nutritional anemia.
• The second major category of nutritional
anemia, macrocytic (MCV above normal),
results from a deficiency in folic acid, or
vitamin B12. [These macrocytic anemias are
commonly called megaloblastic because a
deficiency of either vitamin (or both) causes
accumulation of large, immature RBC
precursors, known as megaloblasts, in the
bone marrow and the blood.]
Co-Enzyme Related Vitamin Chemical Reaction
TPP Thiamine (B1) Oxidative decarboxylase, trans ketolase
FAD, FMN Riboflavin (B2) Oxidation- reduction
NAD, NADP Niacin (B3) Oxidation- reduction
Co-A Pantothenic acid (B5) Acyl group transfer (formation if active acetate)
Pyr.P Pyridoxal (B6) Amino acid formation
Biocytin Biotin (B7) Carboxylation
THF Folic acid (B9) One-carbon fragment metabolism
Methylcobolamine, Cobolamine (B12) Coenzyme for: homocysteine to methionine, methylmalonyl CoA to
Deoxyadenosyl cobolamine succinyl CoA

Ascorbic acid Ascorbic acid (Vit C) Antioxidant, coencyme for hydroxylation (collagen)

Dr. Nada F Abo El-Magd

References:

• Ferrier, D. R., & Harvey, R. A. Lippincott

Illustrated Reviews Series: Biochemistry.
Philadelphia: Wolters Kluwer Health. Sixth, North
American Edition edition-2020